The role of miRNAs in proliferation of colorectal cancer
The role of miRNAs in proliferation of colorectal cancer
Yasaman Peirovy,1,*
1. Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
Introduction: Colorectal cancer (CRC) is known as the third most common cancer as well as the fourth most deadly cancer worldwide. As Western diets and lifestyles have had an increasing impact on human health, a rise in CRC incidence rates has followed. The risk factors for CRC include environment, family history, age, obesity, smoking, alcohol, low physical activity, and poor nutrition. CRC accounts for approximately 10 % of all new cancer cases globally, remaining the second most frequent cause of cancer-related deaths. Identification of the influencing factors and molecular mechanisms in CRC progression and chemoradiotherapy plays a vital role in CRC treatment. MicroRNAs (miRNAs) are a class of small noncoding RNAs which can bind to target mRNA and induce downregulation of target protein through translation inhibition, mRNA cleavage or degradation. A single kind of miRNA can target hundreds of mRNAs, affecting the expression of many genes that are often involved in the pathway of functional interaction. This study's aim was to investigate the role of miRNAs in colorectal cancer.
Methods: this review investigating the role of miRNAs in the proliferation of colorectal cancer has been written from scientific databases such as Science Direct, Springer, Google Scholar, and PubMed.
Results: Unrestricted proliferation of human CRC is the basis of cancer development in which miRNAs play a significant role. Various miRNAs target a variety of proliferation-related genes consisting of miR-143 and miR-145 (miR-143/145). Michael et al. first reported the association between the miR-143/145 cluster and CRC in 2003, and they revealed decreased expression of miR-143/145 in colorectal tissues compared to normal tissues. There is a consensus that miR-143/145 are tumor suppressor miRNAs. In CRC tissues, the downregulation of miR-143 increased the expression of DNMT3A. Upregulated DNMT3A promote CRC progression, which is associated with DNA methylation. Furthermore, Hu et al. demonstrated that PART1 competed with DNMT3A for binding miR-143, which meant that PART1 might also be a useful therapeutic target. miR-145, which is co-expressed in the same cluster with miR-143, was demonstrated to inhibit IGF1R with miR-143 and repress CRC proliferation. Moreover, it was reported that miR-145 served as an oncosuppressor, and CRC cells treated with miR-145 mimics showed a decrease in their proliferation, which also indicated that miR-145 had a potential role in CRC treatment. Another important set of miRNAs, the miR-17~92 cluster, including miR-17, miR-18a, miR-19a, miR-19b-1, miR-20a, and miR-92a, is related to multiple cancers such as lung cancer, prostate cancer, and colorectal cancer. Investigators found that miR-17, miR-106a/b and miR-20a/b could target GABBR1 to regulate GABB signaling during CRC proliferation. miR-17 is the most upregulated member of the miR-17-92 cluster in the evolution of early colon cancer. Investigators reported that miR-17 promoted CRC proliferation by downregulating SIK1 expression. miR-20a and miR-106a have essential roles in CRC proliferation. Zhu et al. reported that upregulation of miR-20a and miR-106a caused the loss of AMER1 (also known as WTX), disrupting the interaction between RHOGDIα and CDC42, which resulted in accelerated CRC proliferation.
Conclusion: In conclusion, miRNA regulate multiple pathways of expression, such as the Hippo, Notch and Wnt/β-catenin signaling pathways, and the involvement of miRNAs plays a pivotal role in CRC proliferation. The Wnt/β-catenin signalling pathway is vital in CRC proliferation. It has been reported that approximately 90 % of CRC cases carry mutations in one of two genes in a typical Wnt/β-catenin signalling pathway, APC or CTNNB1, which has been confirmed in a recent large-scale sequencing project conducted by The Cancer Genome Atlas (TCGA). Mutations in APC or CTNNB1 usually lead to the accumulation of β-catenin, thus activating the Wnt/β-catenin pathway and promoting CRC progression.