Solmaz Shirjang - Academia.edu (original) (raw)
Papers by Solmaz Shirjang
Cellular and molecular biology, 2015
MicroRNAs (miRNAs) are a large class of small noncoding RNAs approximately 22 nucleotides in leng... more MicroRNAs (miRNAs) are a large class of small noncoding RNAs approximately 22 nucleotides in length. They are the main regulators of gene expression, regulating specific oncogenes, tumor suppressors, cancer stem cells and metastasis. MicroRNAs have become valuable to cancer research in recent years. They appear as a significant biomarker in tumorigenesis. Briefly, the capacities of miRNA to identify between tumor and normal tissue, to distinguish between various subgroups of tumors and to foretell results or responses to therapy have attracted scientist's attention to these small RNAs. MicroRNAs' remarkable stability in both the tissue and bloodstream of cancer patients has elevated the possibility that miRNAs may prove to be a novel diagnostic biomarker. This review focuses on the utility of miRNAs as key biomarkers in cancer diagnosis, cancer prognosis and cancer therapy.
Life Sciences, 2021
Mitogen-activated protein kinase (MAPK) signal transduction, as a highly conserved signaling path... more Mitogen-activated protein kinase (MAPK) signal transduction, as a highly conserved signaling pathway, is reported to be involved in various biological events including metabolic reprogramming, cell proliferation, survival, and differentiation. Mutations in key molecules involved in MAPK/ERK signaling and dysregulation of this pathway are very common events in various human malignancies, which makes the MAPK signaling a crucial signaling pathway participating in the regulation of glucose uptake by malignant cells and tumorigenesis. MicroRNAs (miRNAs), as small non-coding RNAs, are critical regulators of gene expression that play key roles in cancer initiation and progression. On the other hand, these small RNAs mutually regulate the MAPK signaling which is often overexpressed in the case of cancer progression; suggesting that crosstalk between miRNAs and this signaling pathway plays a pivotal role in the development of human cancers. Some miRNAs such as miR-20b, miR-34c-3p, miR-152, miR-181a, and miR-302b through inhibiting MAPK signaling, and miR-193a-3p, miR-330-3p, and miR-592 by activating this signaling pathway, play imperative roles in tumorigenesis. Therefore, in this review, we aimed to focus on the interplay between miRNAs and MAPK signaling in the various steps of tumorigenesis, including metabolic regulation, cell proliferation, apoptosis, metastasis, angiogenesis, and drug resistance.
Advanced Pharmaceutical Bulletin, 2020
Purpose: Based on WHO report, colorectal cancer (CRC) is the second cause of death among patients... more Purpose: Based on WHO report, colorectal cancer (CRC) is the second cause of death among patients with cancer worldwide. Dysregulation of miRNAs expressions has been demonstrated in different human cancers, especially CRC. Studies have shown that miR-330 could act as both TS-miR and/or oncomiR in different types of cancers. BACH1 is also identified as a transcription factor, which is involved in ontogenesis. In this study, we evaluated the CRC suppression via silencing of BACH1 by small silencer molecule called miR-330.Methods:Firstly, we analyzed the BACH1, miR-330-3p and miR-330-5p expressions according to the colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ) project established from a patient of the colon and rectal cancer patients in The Cancer Genome Atlas (TCGA) database. The targeting of BACH1 via miR-330 in human CRC cells was evaluated by Vejnar bioinformatics methods, and confirmed by qRT-PCR and western blot analysis. Proliferation was performed by MTT assay. T...
Expert Opinion on Therapeutic Targets, 2020
Despite improved therapeutic strategies for early-stage breast cancer, the most common cancer typ... more Despite improved therapeutic strategies for early-stage breast cancer, the most common cancer type in women, relapse remains common and the underlying mechanisms for this progression remain poorly understood. To gain more insight, we studied the DNA-binding protein HMGA2 in breast cancer development and stemness. We demonstrated that HMGA2 is overexpressed in breast cancer tissues at the mRNA and protein levels (P value <0.0001). HMGA2 knockdown and overexpression in breast cancer cells revealed that HMGA2 promotes cell proliferation and protects against apoptosis via the intrinsic pathway. HMGA2 knockdown also causes cell cycle arrest in G2/M phase. In addition, we found that HMGA2 increases breast cancer cell migration and invasion (P value <0.001) and promotes the acquisition of cancer stem cell features, both in vitro, in colony formation (P value <0.01) and spheroid assays, and in breast cancer tissues. Overexpression of HMGA2 in breast cancer spurs the acquisition of several hallmarks of cancer, including increased cell proliferation, migration, invasion and stemness, and decreased apoptosis. Thus, targeting HMGA2 could represent an effective strategy to block breast cancer progression.
Journal of Cellular Physiology, 2020
This is the author manuscript accepted for publication and undergone full peer review but has not... more This is the author manuscript accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as
Journal of Cellular Physiology, 2019
Behzad Mansoori developed the hypotheses for this research. Behzad Baradaran and Pascal H.G. Duij... more Behzad Mansoori developed the hypotheses for this research. Behzad Baradaran and Pascal H.G. Duijf planned the methodology. Behzad Baradaran and Behzad Mansoori organized, supervised and were responsible for the course of the project and the article. Behzad Baradaran provided personnel, environmental and financial support, tools, and instruments that were vital for the project. Behzad Mansoori and Ali Mohammadi provided biological materials, reagents and referred patients.
![Research paper thumbnail of Corrigendum to “MicroRNAs in cancer cell death pathways: Apoptosis and necroptosis” [Free Radic. Biol. Med. 139 (2019) 1–15]](https://attachments.academia-assets.com/95388578/thumbnails/1.jpg)
](Free Radical Biology and Medicine, 2019
Free Radical Biology and Medicine, 2019
To protect tissues and the organism from disease, potentially harmful cells are removed through p... more To protect tissues and the organism from disease, potentially harmful cells are removed through programmed cell death processes, including apoptosis and necroptosis. These types of cell death are critically controlled by microRNAs (miRNAs). MiRNAs are short RNA molecules that target and inhibit expression of many cellular regulators, including those controlling programmed cell death via the intrinsic (Bcl-2 and Mcl-1), extrinsic (TRAIL and Fas), p53-and endoplasmic reticulum (ER) stress-induced apoptotic pathways, as well as the necroptosis cell death pathway. In this review, we discuss the current knowledge of apoptosis and necroptosis pathways and how these are impaired in cancer cells. We focus on how miRNAs disrupt apoptosis and necroptosis, thereby critically contributing to malignancy. Understanding which and how miRNAs and their targets affect cell death pathways could open up novel therapeutic opportunities for cancer patients. Indeed, restoration of pro-apoptotic tumor suppressor miRNAs (apoptomiRs) or inhibition of oncogenic miRNAs (oncomiRs) represent strategies that are currently being trialed or are already applied as miRNAbased cancer therapies. Therefore, better understanding the cancer type-specific expression of apoptomiRs and oncomiRs and their underlying mechanisms in cell death pathways will not only advance our knowledge, but also continue to provide new opportunities to treat cancer.
Journal of Cellular Physiology, 2019
During breast cancer progression, tumor cells acquire multiple malignant features. The transcript... more During breast cancer progression, tumor cells acquire multiple malignant features. The transcription factors and cell cycle regulators HMGA2 and Bach-1 are overexpressed in several cancers, but the mechanistic understanding of how HMGA2 and Bach-1 promote cancer development has been limited. We found that HMGA2 and Bach-1 are overexpressed in breast cancer tissues and their expression correlates positively in tumors but not in normal tissues. Individual HMGA2 or Bach-1 knockdown downregulates expression of both proteins, suggesting a mutual stabilizing effect between the two proteins. Importantly, combined HMGA2 and Bach-1 knockdown additively decreases cell proliferation, migration, EMT and colony formation, while promoting apoptotic cell death via upregulation of caspase-3 and caspase-9. First the first time, we show that HMGA2 and Bach-1 overexpression in tumors correlate positively and that the proteins cooperatively suppresses a broad range of malignant cellular properties, such as proliferation, migration, clonogenicity and evasion of apoptotic cell death. Thus, our observations suggest that combined targeting of HMGA2 and Bach1 may be an effective therapeutic strategy to treat breast cancer.
Journal of Cellular Physiology, 2019
Estrogen receptors (ERs) are involved in the development of many types of malignant tumors, in pa... more Estrogen receptors (ERs) are involved in the development of many types of malignant tumors, in particular, breast cancer. Among others, ERs affect cell growth, proliferation, and differentiation. The miRNA miR-142-3p has been shown to inhibit carcinogenesis by regulating various cellular processes, including cell cycle progression, cell migration, apoptosis, and invasion. It does so via targeting molecules involved in a range of signaling pathways. We surgically collected twenty estrogen receptor-positive (ERpositive) breast cancer samples, each with matched adjacent normal breast tissue, and measured the expression of miR-142-3p via qRT-PCR. Bioinformatics methods, luciferase reporter assay, qRT-PCR, and Western blot analysis were employed to assess whether miR-142-3p could target ESR1, which encodes the estrogen receptor, in ERpositive breast cancer cells and patient samples. We also restored miRNA expression and performed cell viability, cytotoxicity and colony formation assays. Western blotting and qRT-PCR were used to study the expression of apoptosis and stemness markers. We found that miR-142-3p is down-regulated in ER-positive breast cancers. Restoration of miR-142-3p expression in ER-positive breast cancer cells reduced cell viability, induced apoptosis via the intrinsic pathway and decreased both colony formation and the
Journal of Cellular Physiology, 2018
Background: Breast cancer is the most common type of cancer among women, and despite improved tre... more Background: Breast cancer is the most common type of cancer among women, and despite improved treatments, it remains a major challenge. However, improved This is the author manuscript accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as
Immunological investigations, 2017
Immune cells are recruited into the tumor microenvironment and regulate anti- and pro-tumor signa... more Immune cells are recruited into the tumor microenvironment and regulate anti- and pro-tumor signals. MicroRNAs (miRNAs) markedly control the immune system responses in cancer development. miRNAs that affect the immune system could be interesting targets for immunomodulation against cancer, either through the activation of effector cells or through the down-regulation of regulatory cells. Bioinformatic calculations can predict the immune system and miRNA interactions. In this review, we discuss the most recent studies about miRNA as the main regulator of recruitment and the activation of the immune system in the tumor microenvironment and finally we propose several miRNAs that could serve as therapeutic molecules in the immunotherapy of cancer.
Advanced pharmaceutical bulletin, 2017
Anticancer drugs resistance is a complex process that arises from altering in the drug targets. A... more Anticancer drugs resistance is a complex process that arises from altering in the drug targets. Advances in the DNA microarray, proteomics technology and the development of targeted therapies provide the new strategies to overcome the drug resistance. Although a design of the new chemotherapy agents is growing quickly, effective chemotherapy agent has not been discovered against the advanced stage of cancer (such as invasion and metastasis). The cancer cell resistance against the anticancer agents can be due to many factors such as the individual's genetic differences, especially in tumoral somatic cells. Also, the cancer drug resistance is acquired, the drug resistance can be occurred by different mechanisms, including multi-drug resistance, cell death inhibiting (apoptosis suppression), altering in the drug metabolism, epigenetic and drug targets, enhancing DNA repair and gene amplification. In this review, we outlined the mechanisms of cancer drug resistance and in following,...
Cellular Immunology, 2017
Understanding the role of toll-like receptors (TLRs) in the immunomodulation potential, different... more Understanding the role of toll-like receptors (TLRs) in the immunomodulation potential, differentiation, migration, and survival of mesenchymal stem cells (MSCs) is absolutely vital to fully exploiting their MSC-based therapeutic potential. Furthermore, through recognition of exogenous or endogenous ligands produced upon injury, TLRs have been linked to allograft rejection and maintenance of chronic inflammatory diseases, including Crohn's disease, rheumatoid arthritis. Characterizing the effect of TLRs in biological control of MSCs fate and function could improve our knowledge about the MSC-based cell therapy and immunotherapy. In this paper, we outline the impacts of TLR activation and mechanisms on MSCs immunomodulatory functions, differentiation, migration, and survivability. Moreover, we indicate that the expression patterns of TLRs in MSCs from different sources.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, Jan 16, 2017
Breast cancer has a high prevalence among women worldwide. Tumor invasion and metastasis still re... more Breast cancer has a high prevalence among women worldwide. Tumor invasion and metastasis still remains an open issue that causes most of the therapeutic failures and remains the prime cause of patient mortality. Hence, there is an unmet need to develop the most effective therapeutic approach with the lowest side effects and highest cytotoxicity that will effectively arrest or eradicate metastasis. An MTT assay and scratch test were used to assess the cytotoxicity and migration effects of Urtica dioica on the breast cancer cells. The QRT-PCR was used to study the expression levels of miR-21, MMP1, MMP9, MMP13, CXCR4, vimentin, and E-cadherin. The results of gene expression in tumoral groups confirmed the overexpression of miR-21, MMP1, MMP9, MMP13, vimentin, and CXCR4, and the lower expression of E-cadherin compared to control groups (P<0.05). Moreover, the results of the MTT assay show that Urtica dioica significantly inhibited breast cancer cell proliferation. Moreover, findings...
Biomedicine & Pharmacotherapy, 2016
Due to the chemo resistant nature of cancer cells and adverse effects of current therapies, resea... more Due to the chemo resistant nature of cancer cells and adverse effects of current therapies, researchers are looking for the most efficient therapeutic approach which has the lowest side effects and the highest toxicity on cancer cells. The aim of the present study was to investigate the synergic effect of Urtica dioica extract in combination with paclitaxel on cell death and invasion of human breast cancer MDA-MB-468 cell line. To determine the cytotoxic effects of Urtica dioica extract with paclitaxel, MTT assay was performed. The scratch test was exploited to assess the effects of Urtica dioica, Paclitaxel alone and combination on migration of cancer cells. The expression levels of snail-1, ZEB1, ZEB2, twist, Cdc2, cyclin B1 and Wee1 genes were quantified using qRT-PCR and western blot performed for snail-1expression. The effects of plant extract, Paclitaxel alone and combination on different phases of cell cycle was analyzed using flow cytometry. Results of MTT assay showed that Urtica dioica significantly destroyed cancer cells. Interestingly, Concurrent use of Urtica dioica extract with paclitaxel resulted in decreased IC50 dose of paclitaxel. Moreover, findings of scratch assay exhibited the inhibitory effects of Urtica dioica, Paclitaxel alone and combination on migration of MDA-MB-468 cell line. Our findings also demonstrated that the extract substantially decreased the Snail-1 and related gene expression. Ultimately, Cell cycle arrest occurred at G2/M phase post-treatment by deregulating Cdc2 and wee1. Our results demonstrated that the dichloromethane extract of Urtica dioica inhibit cell growth and migration. Also, Urtica dioica extract substantially increased sensitivity of breast cancer cells to paclitaxel. Therefore, it can be used as a potential candidate for treatment of breast cancer with paclitaxel.
Cell Cycle, 2016
Purpose: The HMGI-C (high mobility group protein isoform I-C) protein is a member of the high-mob... more Purpose: The HMGI-C (high mobility group protein isoform I-C) protein is a member of the high-mobility group AT-hook (HMGA) family of small non-histone chromosomal proteins that can modulate transcription of an ample number of genes. Genome-wide studies reveal upregulation of the HMGI-C gene in many human cancers, which suggests that HMGI-C might play a critical role in the progression of various tumors. However, the exact role of HMGI-C in breast adenocarcinoma has not been made clear. Methods: HMGI-C mRNA expression in breast cancer samples and marginal normal tissues was characterized using qRT-PCR. The cytotoxic effects of HMGI-C siRNA on breast adenocarcinoma cells were determined using MTT assay. Relative HMGI-C mRNA and protein levels were measured by quantitative real-time PCR and western blotting, respectively. Apoptosis detection was done using TUNEL and Annexin-V/PI assays, P53, caspase 3, 9, 8 and Bcl2 proteins evaluated by protein gel blot and miR34a, Let-7a genes investigates by QRT-PCR assay. Cell cycle was analyzed by flow cytometry assay using propidium iodide DNA staining. Results: An overexpression of HMGA2 was revealed with highly statistically significant differences between breast cancer samples and marginal normal tissues (P < 0.0001). HMGI-C siRNA significantly reduced both mRNA and protein expression levels in a 48-hour period after transfection and in a dose-dependent manner. We observed that the knockdown of HMGI-C led to the significant induction of apoptosis via mitochondrial pathway by inducing miR34a and cell cycle arrest in MDA-MB-468 cells in vitro. Conclusions: These results propose that HMGI-C might play a critical role in the progression of breast adenocarcinoma. Here we introduced HMGI-C as a potential therapeutic target for trigger apoptosis and cell cycle arrest in human breast adenocarcinoma. Therefore HMGI-C siRNA may be an effective adjuvant in human breast adenocarcinoma.
Journal of Cellular Biochemistry, 2018
For many years, cancer therapy has appeared to be a challenging issue for researchers and physici... more For many years, cancer therapy has appeared to be a challenging issue for researchers and physicians. By the introduction of novel methods in immunotherapy, the prospect of cancer therapy even more explained than before. Cytokine-induced killer (CIK) cell-based immunotherapy demonstrated to have potentiality in improving clinical outcomes and relieving major side effects of standard treatment options. In addition, given the distinctive features such as high safety, low toxicity effects on healthy cells, numerous clinical trials conducted on CIK cells. Due to the shortcomings that observed in CIK cell immunotherapy alone, arising a tendency to make modifications (combined modality therapy or combination therapy) including the addition of various types of cytokines, genetic engineering, combination with immune checkpoints, and so on. In this review, we have tried to bring forth the latest immunotherapy methods and their overview. We have discussed the combination therapies with CIK cells and the conducted clinical trials. This helps the future studies to use integrated therapies with CIK cells as a promising treatment of many types of cancers. K E Y W O R D S cancer, combined modality therapy, cytokine-induced killer cells, immunotherapy 1 | INTRODUCTION Cancer is one of the main causes of mortalities worldwide. Away from current and existing cancer therapies that, during the last decades, have permanently improved patient survival rate, establishing novel therapeutic methods and working on them seems to be an indispensable issue. 1 Surgical procedures, radiotherapy, and chemotherapy are conventional therapies to treat cancer in most patients with the efficacy of eliminating and destroying primary tumors. However, it must be notified that these conventional procedures are often ineffective in the case of those cancers at aggressive stages. 2 Cancer immunotherapy is a promising therapy enjoying advances in enhancing antitumor immunity. 3 Nowadays, to treat cancers, there are various types of immunotherapies including cancer vaccines, cytokine
Cellular and molecular biology, 2015
MicroRNAs (miRNAs) are a large class of small noncoding RNAs approximately 22 nucleotides in leng... more MicroRNAs (miRNAs) are a large class of small noncoding RNAs approximately 22 nucleotides in length. They are the main regulators of gene expression, regulating specific oncogenes, tumor suppressors, cancer stem cells and metastasis. MicroRNAs have become valuable to cancer research in recent years. They appear as a significant biomarker in tumorigenesis. Briefly, the capacities of miRNA to identify between tumor and normal tissue, to distinguish between various subgroups of tumors and to foretell results or responses to therapy have attracted scientist's attention to these small RNAs. MicroRNAs' remarkable stability in both the tissue and bloodstream of cancer patients has elevated the possibility that miRNAs may prove to be a novel diagnostic biomarker. This review focuses on the utility of miRNAs as key biomarkers in cancer diagnosis, cancer prognosis and cancer therapy.
Life Sciences, 2021
Mitogen-activated protein kinase (MAPK) signal transduction, as a highly conserved signaling path... more Mitogen-activated protein kinase (MAPK) signal transduction, as a highly conserved signaling pathway, is reported to be involved in various biological events including metabolic reprogramming, cell proliferation, survival, and differentiation. Mutations in key molecules involved in MAPK/ERK signaling and dysregulation of this pathway are very common events in various human malignancies, which makes the MAPK signaling a crucial signaling pathway participating in the regulation of glucose uptake by malignant cells and tumorigenesis. MicroRNAs (miRNAs), as small non-coding RNAs, are critical regulators of gene expression that play key roles in cancer initiation and progression. On the other hand, these small RNAs mutually regulate the MAPK signaling which is often overexpressed in the case of cancer progression; suggesting that crosstalk between miRNAs and this signaling pathway plays a pivotal role in the development of human cancers. Some miRNAs such as miR-20b, miR-34c-3p, miR-152, miR-181a, and miR-302b through inhibiting MAPK signaling, and miR-193a-3p, miR-330-3p, and miR-592 by activating this signaling pathway, play imperative roles in tumorigenesis. Therefore, in this review, we aimed to focus on the interplay between miRNAs and MAPK signaling in the various steps of tumorigenesis, including metabolic regulation, cell proliferation, apoptosis, metastasis, angiogenesis, and drug resistance.
Advanced Pharmaceutical Bulletin, 2020
Purpose: Based on WHO report, colorectal cancer (CRC) is the second cause of death among patients... more Purpose: Based on WHO report, colorectal cancer (CRC) is the second cause of death among patients with cancer worldwide. Dysregulation of miRNAs expressions has been demonstrated in different human cancers, especially CRC. Studies have shown that miR-330 could act as both TS-miR and/or oncomiR in different types of cancers. BACH1 is also identified as a transcription factor, which is involved in ontogenesis. In this study, we evaluated the CRC suppression via silencing of BACH1 by small silencer molecule called miR-330.Methods:Firstly, we analyzed the BACH1, miR-330-3p and miR-330-5p expressions according to the colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ) project established from a patient of the colon and rectal cancer patients in The Cancer Genome Atlas (TCGA) database. The targeting of BACH1 via miR-330 in human CRC cells was evaluated by Vejnar bioinformatics methods, and confirmed by qRT-PCR and western blot analysis. Proliferation was performed by MTT assay. T...
Expert Opinion on Therapeutic Targets, 2020
Despite improved therapeutic strategies for early-stage breast cancer, the most common cancer typ... more Despite improved therapeutic strategies for early-stage breast cancer, the most common cancer type in women, relapse remains common and the underlying mechanisms for this progression remain poorly understood. To gain more insight, we studied the DNA-binding protein HMGA2 in breast cancer development and stemness. We demonstrated that HMGA2 is overexpressed in breast cancer tissues at the mRNA and protein levels (P value <0.0001). HMGA2 knockdown and overexpression in breast cancer cells revealed that HMGA2 promotes cell proliferation and protects against apoptosis via the intrinsic pathway. HMGA2 knockdown also causes cell cycle arrest in G2/M phase. In addition, we found that HMGA2 increases breast cancer cell migration and invasion (P value <0.001) and promotes the acquisition of cancer stem cell features, both in vitro, in colony formation (P value <0.01) and spheroid assays, and in breast cancer tissues. Overexpression of HMGA2 in breast cancer spurs the acquisition of several hallmarks of cancer, including increased cell proliferation, migration, invasion and stemness, and decreased apoptosis. Thus, targeting HMGA2 could represent an effective strategy to block breast cancer progression.
Journal of Cellular Physiology, 2020
This is the author manuscript accepted for publication and undergone full peer review but has not... more This is the author manuscript accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as
Journal of Cellular Physiology, 2019
Behzad Mansoori developed the hypotheses for this research. Behzad Baradaran and Pascal H.G. Duij... more Behzad Mansoori developed the hypotheses for this research. Behzad Baradaran and Pascal H.G. Duijf planned the methodology. Behzad Baradaran and Behzad Mansoori organized, supervised and were responsible for the course of the project and the article. Behzad Baradaran provided personnel, environmental and financial support, tools, and instruments that were vital for the project. Behzad Mansoori and Ali Mohammadi provided biological materials, reagents and referred patients.
Free Radical Biology and Medicine, 2019
Free Radical Biology and Medicine, 2019
To protect tissues and the organism from disease, potentially harmful cells are removed through p... more To protect tissues and the organism from disease, potentially harmful cells are removed through programmed cell death processes, including apoptosis and necroptosis. These types of cell death are critically controlled by microRNAs (miRNAs). MiRNAs are short RNA molecules that target and inhibit expression of many cellular regulators, including those controlling programmed cell death via the intrinsic (Bcl-2 and Mcl-1), extrinsic (TRAIL and Fas), p53-and endoplasmic reticulum (ER) stress-induced apoptotic pathways, as well as the necroptosis cell death pathway. In this review, we discuss the current knowledge of apoptosis and necroptosis pathways and how these are impaired in cancer cells. We focus on how miRNAs disrupt apoptosis and necroptosis, thereby critically contributing to malignancy. Understanding which and how miRNAs and their targets affect cell death pathways could open up novel therapeutic opportunities for cancer patients. Indeed, restoration of pro-apoptotic tumor suppressor miRNAs (apoptomiRs) or inhibition of oncogenic miRNAs (oncomiRs) represent strategies that are currently being trialed or are already applied as miRNAbased cancer therapies. Therefore, better understanding the cancer type-specific expression of apoptomiRs and oncomiRs and their underlying mechanisms in cell death pathways will not only advance our knowledge, but also continue to provide new opportunities to treat cancer.
Journal of Cellular Physiology, 2019
During breast cancer progression, tumor cells acquire multiple malignant features. The transcript... more During breast cancer progression, tumor cells acquire multiple malignant features. The transcription factors and cell cycle regulators HMGA2 and Bach-1 are overexpressed in several cancers, but the mechanistic understanding of how HMGA2 and Bach-1 promote cancer development has been limited. We found that HMGA2 and Bach-1 are overexpressed in breast cancer tissues and their expression correlates positively in tumors but not in normal tissues. Individual HMGA2 or Bach-1 knockdown downregulates expression of both proteins, suggesting a mutual stabilizing effect between the two proteins. Importantly, combined HMGA2 and Bach-1 knockdown additively decreases cell proliferation, migration, EMT and colony formation, while promoting apoptotic cell death via upregulation of caspase-3 and caspase-9. First the first time, we show that HMGA2 and Bach-1 overexpression in tumors correlate positively and that the proteins cooperatively suppresses a broad range of malignant cellular properties, such as proliferation, migration, clonogenicity and evasion of apoptotic cell death. Thus, our observations suggest that combined targeting of HMGA2 and Bach1 may be an effective therapeutic strategy to treat breast cancer.
Journal of Cellular Physiology, 2019
Estrogen receptors (ERs) are involved in the development of many types of malignant tumors, in pa... more Estrogen receptors (ERs) are involved in the development of many types of malignant tumors, in particular, breast cancer. Among others, ERs affect cell growth, proliferation, and differentiation. The miRNA miR-142-3p has been shown to inhibit carcinogenesis by regulating various cellular processes, including cell cycle progression, cell migration, apoptosis, and invasion. It does so via targeting molecules involved in a range of signaling pathways. We surgically collected twenty estrogen receptor-positive (ERpositive) breast cancer samples, each with matched adjacent normal breast tissue, and measured the expression of miR-142-3p via qRT-PCR. Bioinformatics methods, luciferase reporter assay, qRT-PCR, and Western blot analysis were employed to assess whether miR-142-3p could target ESR1, which encodes the estrogen receptor, in ERpositive breast cancer cells and patient samples. We also restored miRNA expression and performed cell viability, cytotoxicity and colony formation assays. Western blotting and qRT-PCR were used to study the expression of apoptosis and stemness markers. We found that miR-142-3p is down-regulated in ER-positive breast cancers. Restoration of miR-142-3p expression in ER-positive breast cancer cells reduced cell viability, induced apoptosis via the intrinsic pathway and decreased both colony formation and the
Journal of Cellular Physiology, 2018
Background: Breast cancer is the most common type of cancer among women, and despite improved tre... more Background: Breast cancer is the most common type of cancer among women, and despite improved treatments, it remains a major challenge. However, improved This is the author manuscript accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as
Immunological investigations, 2017
Immune cells are recruited into the tumor microenvironment and regulate anti- and pro-tumor signa... more Immune cells are recruited into the tumor microenvironment and regulate anti- and pro-tumor signals. MicroRNAs (miRNAs) markedly control the immune system responses in cancer development. miRNAs that affect the immune system could be interesting targets for immunomodulation against cancer, either through the activation of effector cells or through the down-regulation of regulatory cells. Bioinformatic calculations can predict the immune system and miRNA interactions. In this review, we discuss the most recent studies about miRNA as the main regulator of recruitment and the activation of the immune system in the tumor microenvironment and finally we propose several miRNAs that could serve as therapeutic molecules in the immunotherapy of cancer.
Advanced pharmaceutical bulletin, 2017
Anticancer drugs resistance is a complex process that arises from altering in the drug targets. A... more Anticancer drugs resistance is a complex process that arises from altering in the drug targets. Advances in the DNA microarray, proteomics technology and the development of targeted therapies provide the new strategies to overcome the drug resistance. Although a design of the new chemotherapy agents is growing quickly, effective chemotherapy agent has not been discovered against the advanced stage of cancer (such as invasion and metastasis). The cancer cell resistance against the anticancer agents can be due to many factors such as the individual's genetic differences, especially in tumoral somatic cells. Also, the cancer drug resistance is acquired, the drug resistance can be occurred by different mechanisms, including multi-drug resistance, cell death inhibiting (apoptosis suppression), altering in the drug metabolism, epigenetic and drug targets, enhancing DNA repair and gene amplification. In this review, we outlined the mechanisms of cancer drug resistance and in following,...
Cellular Immunology, 2017
Understanding the role of toll-like receptors (TLRs) in the immunomodulation potential, different... more Understanding the role of toll-like receptors (TLRs) in the immunomodulation potential, differentiation, migration, and survival of mesenchymal stem cells (MSCs) is absolutely vital to fully exploiting their MSC-based therapeutic potential. Furthermore, through recognition of exogenous or endogenous ligands produced upon injury, TLRs have been linked to allograft rejection and maintenance of chronic inflammatory diseases, including Crohn's disease, rheumatoid arthritis. Characterizing the effect of TLRs in biological control of MSCs fate and function could improve our knowledge about the MSC-based cell therapy and immunotherapy. In this paper, we outline the impacts of TLR activation and mechanisms on MSCs immunomodulatory functions, differentiation, migration, and survivability. Moreover, we indicate that the expression patterns of TLRs in MSCs from different sources.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, Jan 16, 2017
Breast cancer has a high prevalence among women worldwide. Tumor invasion and metastasis still re... more Breast cancer has a high prevalence among women worldwide. Tumor invasion and metastasis still remains an open issue that causes most of the therapeutic failures and remains the prime cause of patient mortality. Hence, there is an unmet need to develop the most effective therapeutic approach with the lowest side effects and highest cytotoxicity that will effectively arrest or eradicate metastasis. An MTT assay and scratch test were used to assess the cytotoxicity and migration effects of Urtica dioica on the breast cancer cells. The QRT-PCR was used to study the expression levels of miR-21, MMP1, MMP9, MMP13, CXCR4, vimentin, and E-cadherin. The results of gene expression in tumoral groups confirmed the overexpression of miR-21, MMP1, MMP9, MMP13, vimentin, and CXCR4, and the lower expression of E-cadherin compared to control groups (P<0.05). Moreover, the results of the MTT assay show that Urtica dioica significantly inhibited breast cancer cell proliferation. Moreover, findings...
Biomedicine & Pharmacotherapy, 2016
Due to the chemo resistant nature of cancer cells and adverse effects of current therapies, resea... more Due to the chemo resistant nature of cancer cells and adverse effects of current therapies, researchers are looking for the most efficient therapeutic approach which has the lowest side effects and the highest toxicity on cancer cells. The aim of the present study was to investigate the synergic effect of Urtica dioica extract in combination with paclitaxel on cell death and invasion of human breast cancer MDA-MB-468 cell line. To determine the cytotoxic effects of Urtica dioica extract with paclitaxel, MTT assay was performed. The scratch test was exploited to assess the effects of Urtica dioica, Paclitaxel alone and combination on migration of cancer cells. The expression levels of snail-1, ZEB1, ZEB2, twist, Cdc2, cyclin B1 and Wee1 genes were quantified using qRT-PCR and western blot performed for snail-1expression. The effects of plant extract, Paclitaxel alone and combination on different phases of cell cycle was analyzed using flow cytometry. Results of MTT assay showed that Urtica dioica significantly destroyed cancer cells. Interestingly, Concurrent use of Urtica dioica extract with paclitaxel resulted in decreased IC50 dose of paclitaxel. Moreover, findings of scratch assay exhibited the inhibitory effects of Urtica dioica, Paclitaxel alone and combination on migration of MDA-MB-468 cell line. Our findings also demonstrated that the extract substantially decreased the Snail-1 and related gene expression. Ultimately, Cell cycle arrest occurred at G2/M phase post-treatment by deregulating Cdc2 and wee1. Our results demonstrated that the dichloromethane extract of Urtica dioica inhibit cell growth and migration. Also, Urtica dioica extract substantially increased sensitivity of breast cancer cells to paclitaxel. Therefore, it can be used as a potential candidate for treatment of breast cancer with paclitaxel.
Cell Cycle, 2016
Purpose: The HMGI-C (high mobility group protein isoform I-C) protein is a member of the high-mob... more Purpose: The HMGI-C (high mobility group protein isoform I-C) protein is a member of the high-mobility group AT-hook (HMGA) family of small non-histone chromosomal proteins that can modulate transcription of an ample number of genes. Genome-wide studies reveal upregulation of the HMGI-C gene in many human cancers, which suggests that HMGI-C might play a critical role in the progression of various tumors. However, the exact role of HMGI-C in breast adenocarcinoma has not been made clear. Methods: HMGI-C mRNA expression in breast cancer samples and marginal normal tissues was characterized using qRT-PCR. The cytotoxic effects of HMGI-C siRNA on breast adenocarcinoma cells were determined using MTT assay. Relative HMGI-C mRNA and protein levels were measured by quantitative real-time PCR and western blotting, respectively. Apoptosis detection was done using TUNEL and Annexin-V/PI assays, P53, caspase 3, 9, 8 and Bcl2 proteins evaluated by protein gel blot and miR34a, Let-7a genes investigates by QRT-PCR assay. Cell cycle was analyzed by flow cytometry assay using propidium iodide DNA staining. Results: An overexpression of HMGA2 was revealed with highly statistically significant differences between breast cancer samples and marginal normal tissues (P < 0.0001). HMGI-C siRNA significantly reduced both mRNA and protein expression levels in a 48-hour period after transfection and in a dose-dependent manner. We observed that the knockdown of HMGI-C led to the significant induction of apoptosis via mitochondrial pathway by inducing miR34a and cell cycle arrest in MDA-MB-468 cells in vitro. Conclusions: These results propose that HMGI-C might play a critical role in the progression of breast adenocarcinoma. Here we introduced HMGI-C as a potential therapeutic target for trigger apoptosis and cell cycle arrest in human breast adenocarcinoma. Therefore HMGI-C siRNA may be an effective adjuvant in human breast adenocarcinoma.
Journal of Cellular Biochemistry, 2018
For many years, cancer therapy has appeared to be a challenging issue for researchers and physici... more For many years, cancer therapy has appeared to be a challenging issue for researchers and physicians. By the introduction of novel methods in immunotherapy, the prospect of cancer therapy even more explained than before. Cytokine-induced killer (CIK) cell-based immunotherapy demonstrated to have potentiality in improving clinical outcomes and relieving major side effects of standard treatment options. In addition, given the distinctive features such as high safety, low toxicity effects on healthy cells, numerous clinical trials conducted on CIK cells. Due to the shortcomings that observed in CIK cell immunotherapy alone, arising a tendency to make modifications (combined modality therapy or combination therapy) including the addition of various types of cytokines, genetic engineering, combination with immune checkpoints, and so on. In this review, we have tried to bring forth the latest immunotherapy methods and their overview. We have discussed the combination therapies with CIK cells and the conducted clinical trials. This helps the future studies to use integrated therapies with CIK cells as a promising treatment of many types of cancers. K E Y W O R D S cancer, combined modality therapy, cytokine-induced killer cells, immunotherapy 1 | INTRODUCTION Cancer is one of the main causes of mortalities worldwide. Away from current and existing cancer therapies that, during the last decades, have permanently improved patient survival rate, establishing novel therapeutic methods and working on them seems to be an indispensable issue. 1 Surgical procedures, radiotherapy, and chemotherapy are conventional therapies to treat cancer in most patients with the efficacy of eliminating and destroying primary tumors. However, it must be notified that these conventional procedures are often ineffective in the case of those cancers at aggressive stages. 2 Cancer immunotherapy is a promising therapy enjoying advances in enhancing antitumor immunity. 3 Nowadays, to treat cancers, there are various types of immunotherapies including cancer vaccines, cytokine