Colorectal Cancer: From the Genetic Model to Posttranscriptional Regulation by Noncoding RNAs

Abstract

Colorectal cancer is the third most common form of cancer in developed countries and, despite the improvements achieved in its treatment options, remains as one of the main causes of cancer-related death. In this review, we first focus on colorectal carcinogenesis and on the genetic and epigenetic alterations involved. In addition, noncoding RNAs have been shown to be important regulators of gene expression. We present a general overview of what is known about these molecules and their role and dysregulation in cancer, with a special focus on the biogenesis, characteristics, and function of microRNAs. These molecules are important regulators of carcinogenesis, progression, invasion, angiogenesis, and metastases in cancer, including colorectal cancer. For this reason, miRNAs can be used as potential biomarkers for diagnosis, prognosis, and efficacy of chemotherapeutic treatments, or even as therapeutic agents, or as targets by themselves. Thus, this review highlights the importance of miRNAs in the development, progression, diagnosis, and therapy of colorectal cancer and summarizes current therapeutic approaches for the treatment of colorectal cancer.

Identification of a miRNA‑mRNA network associated with lymph node metastasis in colorectal cancer

“…The results of the present study indicated that miR-612, miR-1-3p, miR-133b and miR-133a-3p may synergistically regulate SP1 expression at the translational level, and subsequently Sp1 may further adjust MMP11 and MMP14 expression at the transcriptional level to promote the invasion and metastasis of CRC. TP53 is a tumor suppressor gene, and its expression changes promote occurrence and progression of CRC (50). The data from the present study suggested that miR-155-3p and miR-612 may be involved in the regulation of TP53 expression, and may participate in the malignant development of colorectal cancer through TP53 -mediated ACTA2 and S100 calcium-binding protein A2.…”

Roles of long non-coding RNAs in colorectal cancer tumorigenesis: A Review

“…Moreover, they act as gene expression regulators at the transcriptional, post-transcriptional, and epigenetic levels (21). A recent report highlighted the involvement of lncRNAs in CRC chemoresistance through several mechanisms, such as epigenetic modification, interaction with other miRNAs, acting as structural RNAs in scaffolding ribonuclear protein complexes, and regulating the expression of several genes that are involved in key cellular processes, including invasion and metastasis, apoptosis, cell proliferation and differentiation (25). Additionally, lncRNAs may be classed as competing endogenous RNAs (ceRNAs) that inhibit the targets of miRNAs; therefore, they act as miRNA sponges that regulate the migration, invasion and proliferation of CRC cells (26).…”

Effect of dietary components on miRNA and colorectal carcinogenesis

“…Several biological functions of miRNA have been reported to be related to various disease mechanisms, regulation of cellular activities and cancer progression [ 66 – 69 ].…”