Angioregulatory microRNAs in Colorectal Cancer (original) (raw)
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Gene Reports, 2020
Colorectal cancer (CRC) is the main cause of cancer-related mortalities, worldwide and is the most prevalent cancer of the gastrointestinal tract. Different techniques exist to diagnose CRC including colonoscopy, sigmoi-doscopy, and plasma miRNA test. This study evaluates the important miRNAs and main genes playing role in metastasis, angiogenesis and apoptosis that can be considered as prognostic and progression markers of CRC. We have measured the expression levels of the miRNAs, and multiple genes related to angiogenesis, metastasis and apoptosis in 45 paired samples of CRC tissue specimens and adjacent normal mucosa tissues obtained from 45 patients with CRC utilizing Real-time PCR. We have also analyzed the relationship between the expression of these genes and clinic pathological features. Results showed that the expression levels of angiogenesis genes (PGE-2, VEGF, Vimentin, CD105, CXCL-1, and IGFBP-7), metastatic genes (IGF-1R, Snail-1, and MMP-7) and apoptotic genes (Bcl-2, Bcl-xl, and NF-κβ1) were significantly higher in cancer tissues. But the expression levels of E-cadherin, AdipoR1, Claudin-7, Bax, Puma, and Noxa, were notably lower in cancer tissues. Additionally, it was revealed that miRNAs (miR-21, miR-19a, miR-18a, and miR-92a) expression levels were in higher levels in cancer tissues when compared to the normal tissues. In contrast, the expression levels of miR-31, and miR-139-5p were significantly lower in cancer tissues. It is hoped that, by measuring the metastasis, angiogenesis and apoptosis resistance associated miRNAs expression, better treatment results would be achieved in CRC treatment .
MicroRNA in colorectal cancer: new perspectives for diagnosis, prognosis and treatment
Journal of gastrointestinal and liver diseases : JGLD, 2013
Colorectal cancer (CRC) is a common condition and represents a lethal disease, following a sequential progression from adenoma to carcinoma. Interfering with such natural history of CRC offers clues to prevention and cure, but current screening methods for CRC are still limited by unsatisfactory sensitivity and specificity. Novel diagnostic, prognostic tools are therefore being actively investigated for CRC. The discovery of microRNAs (miRNAs) has led to active research focusing on their role in cancer and several crucial pathways involving angiogenesis, cancer-stem-cell biology, epithelial-mesenchymal transition, formation of metastasis, and drug resistance. MiRNAs might soon represent novel prognostic and diagnostic tools in patients at high risk of CRC or being diagnosed with CRC. MiRNA might prove useful also as therapeutic tools, since dysregulation of miRNAs in cancer cells results in higher levels of messenger RNA (mRNA) specific to tumor promoter genes or tumor suppressor ge...
MicroRNA–mRNA Interactions in Colorectal Cancer and Their Role in Tumor Progression
MicroRNAs (miRNA/miR) play an important role in gene regulatory networks through targeting mRNAs. They are involved in diverse biological processes such as cell proliferation, differentiation, angiogenesis, and apoptosis. Due to their pivotal effects on multiple genes and pathways, dysregulated miRNAs have been reported to be associated with different diseases, including colorectal cancer (CRC). Recent evidence indicates that aberrant miRNA expression is tightly linked with the initiation and progression of CRC. To elucidate the influence of miRNA regulation in CRC, it is critical to identify dysregulated miRNAs, their target mRNA genes and their involvement in gene regulatory and signaling networks. Various experimental and computational studies have been conducted to decipher the function of miRNAs involved in CRC. Experimental studies that are used for this purpose can be classified into two categories: direct/individual and indirect/high-throughput gene expression studies. Here we review miRNA target identification studies related to CRC with an emphasis on experimental data based on Luciferase reporter assays. Recent advances in determining the function of miRNAs and the signaling pathways they are involved in have also been summarized. The review helps bioinformaticians and biologists to find extensive information about downstream targets of dysregulated miRNAs, and their pro-/anti-CRC effects.
MicroRNAs in the prognosis and therapy of colorectal cancer: From bench to bedside
World journal of gastroenterology, 2018
MicroRNAs (miRNAs) are small, single-stranded, noncoding RNAs that can post-transcriptionally regulate the expression of various oncogenes and tumor suppressor genes. Dysregulated expression of many miRNAs have been shown to mediate the signaling pathways critical in the multistep carcinogenesis of colorectal cancer (CRC). MiRNAs are stable and protected from RNase-mediated degradation, thereby enabling its detection in biological fluids and archival tissues for biomarker studies. This review focuses on the role and application of miRNAs in the prognosis and therapy of CRC. While stage II CRC is potentially curable by surgical resection, a significant percentage of stage II CRC patients do develop recurrence. MiRNA biomarkers may be used to stratify such high-risk population for adjuvant chemotherapy to provide better prognoses. Growing evidence also suggests that miRNAs are involved in the metastatic process of CRC. Certain of these miRNAs may thus be used as prognostic biomarkers ...
MicroRNAs in colorectal cancer: Role in metastasis and clinical perspectives
World Journal of Gastroenterology, 2014
Colorectal cancer (CRC) is the third most common malignancy and the third leading cause of cancer related deaths in the United States. Almost 90% of the patients diagnosed with CRC die due to metastases. MicroRNAs (miRNAs) are evolutionarily conserved molecules that modulate the expression of their target genes post-transcriptionally, and they may participate in various physiological and pathological processes including CRC metastasis by influencing various factors in the human body. Recently, the role miRNAs play throughout the CRC metastatic cascade has gain attention. Many studies have been published to link them with CRC metastasis. In this review, we will briefly discuss metastatic steps in the light of miRNAs, along with their target genes. We will discuss how the aberration in the expression of miRNAs leads to the formation of CRC by effecting the regulation of their target genes.
MicroRNAs in colorectal cancer: translation of molecular biology into clinical application
Molecular Cancer, 2009
MicroRNAs (miRNAs) are small non-coding RNAs 18-25 nucleotides in length that downregulate gene expression during various crucial cell processes such as apoptosis, differentiation and development. Changes in the expression profiles of miRNAs have been observed in a variety of human tumors, including colorectal cancer (CRC). Functional studies indicate that miRNAs act as tumor suppressors and oncogenes. These findings significantly extend Vogelstein's model of CRC pathogenesis and have shown great potential for miRNAs as a novel class of therapeutic targets. Several investigations have also described the ability of miRNA expression profiles to predict prognosis and response to selected treatments in CRC patients, and support diagnosis of CRC among cancer of unknown primary site. miRNAs' occurrence has been repeatedly observed also in serum and plasma, and miRNAs as novel minimally invasive biomarkers have indicated reasonable sensitivity for CRC detection and compare favorably with the fecal occult blood test. In this review, we summarize the knowledge regarding miRNAs' functioning in CRC while emphasizing their significance in pathogenetic signaling pathways and their potential to serve as disease biomarkers and novel therapeutic targets.
Identification and functional screening of microRNAs highly deregulated in colorectal cancer
Journal of Cellular and Molecular Medicine, 2012
MicroRNAs (miRNAs) constitute a robust regulatory network with post-transcriptional regulatory efficiency for almost one half of human coding genes, including oncogenes and tumour suppressors. We determined the expression profile of 667 miRNAs in colorectal cancer (CRC) tissues and paired non-tumoural tissues and identified 42 differentially expressed miRNAs. We chose miR-215, miR-375, miR-378, miR-422a and miR-135b for further validation on an independent cohort of 125 clinically characterized CRC patients and for in vitro analyses. MiR-215, miR-375, miR-378 and miR-422a were significantly decreased, whereas miR-135b was increased in CRC tumour tissues. Levels of miR-215 and miR-422a correlated with clinical stage. MiR-135b was associated with higher pre-operative serum levels of CEA and CA19-9. In vitro analyses showed that ectopic expression of miR-215 decreases viability and migration, increases apoptosis and promotes cell cycle arrest in DLD-1 and HCT-116 colon cancer cell lines. Similarly, overexpression of miR-375 and inhibition of miR-135b led to decreased viability. Finally, restoration of miR-378, miR-422a and miR-375 inhibited G1/S transition. These findings indicate that miR-378, miR-375, miR-422a and miR-215 play an important role in CRC as tumour suppressors, whereas miR-135b functions as an oncogene; both groups of miRNA contribute to CRC pathogenesis.
MicroRNAs in colorectal cancer: Function, dysregulation and potential as novel biomarkers
European Journal of Surgical Oncology (EJSO), 2011
Background: MicroRNAs (miRNAs) are short non-coding segments of RNA which are involved in normal cellular development and proliferation. Recent studies have identified altered miRNA expression in both tumour tissues and circulation in the presence of colorectal cancer. These altered expression patterns may serve as novel biomarkers for colorectal cancer. This review explores recent developments in this rapidly evolving field. Methods: A thorough literature search was performed to identify studies describing miRNA expression in colorectal cancer. Specific areas of interest included miRNA expression patterns in relation to development, diagnosis, progression and recurrence of disease, and potential future therapeutic applications. Results: MiRNAs are associated with the development and progression of colorectal cancer. These may be either overexpressed or underexpressed (depending on the specific miRNA). Although there are fewer published studies regarding circulating miRNAs, these appear to be reflective of alterations in tissue expression and may have a potential role as minimally invasive biomarkers.
MicroRNAs in colorectal cancer
International Journal of Research in Medical Sciences, 2019
Colorectal cancer (CRC) is the third most common type of cancer worldwide, currently representing the most common gastrointestinal cancer with 13% of all malignant tumors. MicroRNAs (miRNAs) are small non-coding RNAs that repress the translation of target genes. Since their discovery, they have been shown to play an important role in the development of cancer, since they can act as tumor suppressors or oncogenes. A literature review was performed in different databases such as Medline, PubMed, Cochrane, nature, Wolters Kluwer, ScienceDirect, Scopus, SpringerLink, Wiley Online Library. Studies were included from 2003 to 2018. Colorectal cancer presents genetic heterogeneity, because it can develop in different ways, the pathway through which cancer occurs depends on the gene initially altered. The aberrant expression of microRNAs is implicated in the development of colorectal cancer and its progression. Three existing steps in the maturation of the microRNAs have been identified: 1) transcription of the pri-miRNA, 2) cleavage in the nucleus to form the pre-miRNA and 3) a final excision in the cytoplasm to form the mature microRNA. It has been discovered that miRNAs have an impact on cell proliferation, apoptosis, stress response, maintenance of stem cell potency and metabolism, all important factors in the etiology of cancer. The data analyzed in this article highlights the importance of the study of microRNAs in colorectal cancer, however, for the carcinogenic process, progression, therapeutic management and prognosis, more multicenter randomized clinical trials are needed with a detailed analysis.
International Journal of Molecular Sciences
We recently determined the RNA sequencing-based microRNA (miRNA) expression signature of colorectal cancer (CRC). Analysis of the signature showed that the expression of both strands of pre-miR-139 (miR-139-5p, the guide strand, and miR-139-3p, the passenger strand) was significantly reduced in CRC tissues. Transient transfection assays revealed that expression of miR-139-3p blocked cancer cell malignant transformation (e.g., cell proliferation, migration, and invasion). Notably, expression of miR-139-3p markedly blocked RAC-alpha serine/threonine-protein kinase (AKT) phosphorylation in CRC cells. A combination of in silico database and gene expression analyses of miR-139-3p-transfected cells revealed 29 putative targets regulated by miR-139-3p in CRC cells. RNA immunoprecipitation analysis using an Argonaute2 (AGO2) antibody revealed that KRT80 was efficiently incorporated into the RNA-induced silencing complex. Aberrant expression of Keratin 80 (KRT80) was detected in CRC clinical...