Effect of dietary components on miRNA and colorectal carcinogenesis (original) (raw)

The Role of Bioactive Dietary Components in Modulating miRNA Expression in Colorectal Cancer

Nutrients, 2016

Colorectal cancer is the third most common cancer in the world and considered to be one of the most diet-related types of cancer. Extensive research has been conducted but still the link between diet and colorectal cancer is complex. Recent studies have highlight microRNAs (miRNAs) as key players in cancer-related pathways in the context of dietary modulation. MicroRNAs are involved in most biological processes related to tumor development and progression; therefore, it is of great interest to understand the underlying mechanisms by which dietary patterns and components influence the expression of these powerful molecules in colorectal cancer. In this review, we discuss relevant dietary patterns in terms of miRNAs modulation in colorectal cancer, as well as bioactive dietary components able to modify gene expression through changes in miRNA expression. Furthermore, we emphasize on protective components such as resveratrol, curcumin, quercetin, α-mangostin, omega-3 fatty acids, vitam...

Manipulating MiRNA Expression: a Novel Approach for Colon Cancer Prevention and Chemotherapy

Current Pharmacology Reports, 2015

Small non-coding RNA has been implicated in the control of various cellular processes such as proliferation, apoptosis, and differentiation. About 50 % of the miRNA genes are positioned in cancer-associated genomic regions. Several studies have shown that miRNA expression is deregulated in cancer and modulating their expression has reversed the cancer phenotype. Therefore, mechanisms to modulate microRNA (miRNA) activity have provided a novel opportunity for cancer prevention and therapy. In addition, a common cause for development of colorectal cancers is environmental and lifestyle factors. One such factor, diet has been shown to modulate miRNA expression in colorectal cancer patients. In this chapter, we will summarize the work demonstrating that miRNAs are novel promising drug targets for cancer chemoprevention and therapy. Improved delivery, increased stability, and enhanced regulation of off-target effects will overcome the current challenges of this exciting approach in the field of cancer prevention and therapy.

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.

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.

MicroRNA manipulation in colorectal cancer cells: from laboratory to clinical application

Journal of Translational Medicine, 2012

The development of Colorectal Cancer (CRC) follows a sequential progression from adenoma to the carcinoma. Therefore, opportunities exist to interfere with the natural course of disease development and progression. Dysregulation of microRNAs (miRNAs) in cancer cells indirectly results in higher levels of messenger RNA (mRNA) specific to tumour promoter genes or tumour suppressor genes. This narrative review aims to provide a comprehensive review of the literature about the manipulation of oncogenic or tumour suppressor miRNAs in colorectal cancer cells for the purpose of development of anticancer therapies. A literature search identified studies describing manipulation of miRNAs in colorectal cancer cells in vivo and in vitro. Studies were also included to provide an update on the role of miRNAs in CRC development, progression and diagnosis. Strategy based on restoration of silenced miRNAs or inhibition of over expressed miRNAs has opened a new area of research in cancer therapy. In this review article different techniques for miRNA manipulation are reviewed and their utility for colorectal cancer therapy has been discussed in detail. Restoration of normal equilibrium for cancer related miRNAs can result in inhibition of tumour growth, apoptosis, blocking of invasion, angiogenesis and metastasis. Furthermore, drug resistant cancer cells can be turned into drug sensitive cells on alteration of specific miRNAs in cancer cells. MiRNA modulation in cancer cells holds great potential to replace current anticancer therapies. However, further work is needed on tissue specific delivery systems and strategies to avoid side effects.

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.

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...

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 ...

Insights into the Role of microRNAs in Colorectal Cancer (CRC) Metabolism

Cancers

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers, with a high mortality rate globally. The pathophysiology of CRC is mainly initiated by alteration in gene expression, leading to dysregulation in multiple signalling pathways and cellular processes. Metabolic reprogramming is one of the important cancer hallmarks in CRC, which involves the adaptive changes in tumour cell metabolism to sustain the high energy requirements for rapid cell proliferation. There are several mechanisms in the metabolic reprogramming of cancer cells, such as aerobic glycolysis, oxidative phosphorylation, lactate and fatty acids metabolism. MicroRNAs (miRNAs) are a class of non-coding RNAs that are responsible for post-transcriptional regulation of gene expression. Differential expression of miRNAs has been shown to play an important role in different aspects of tumorigenesis, such as proliferation, apoptosis, and drug resistance, as well as metabolic reprogramming. Increasing evidence ...

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.