MicroRNA Methylome Signature and Their Functional Roles in Colorectal Cancer Diagnosis, Prognosis, and Chemoresistance

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Despite significant advances in the diagnostic services and patient care, several gaps remain to be addressed, from early detection, to identifying prognostic variables, effective treatment for the metastatic disease, and the implementation of tailored treatment strategies. MicroRNAs, the short non-coding RNA species, are deregulated in CRC and play a significant role in the occurrence and progression. Nevertheless, microRNA research has historically been based on expression levels to determine its biological significance. The exact mechanism underpinning microRNA deregulation in cancer has yet to be elucidated, but several studies have demonstrated that epigenetic mechanisms play important roles in the regulation of microRNA expression, particularly DNA methylation. However, the methylation profiles of microRNAs remain unknown in CRC patients. Methylation is the next major paradigm shift in cancer detection since large-scale epigenetic alterations are potentially better in identifying and classifying cancers at an earlier stage than somatic mutations. This review aims to provide insight into the current state of understanding of microRNA methylation in CRC. The new knowledge from this study can be utilized for personalized health diagnostics, disease prediction, and monitoring of treatment.

Circulating miRNA Expression Profiles and Machine Learning Models in Association with Response to Irinotecan-Based Treatment in Metastatic Colorectal Cancer

“…Despite the fact that miRNA biogenesis is a highly controlled process, miRNA dysregulation has been directly associated with tumorigenesis and multiple cancer types, including CRC [4]. The differential expression of miRNAs has also been correlated with the molecular profile of CRC, tumor size and location (left versus right colon), presence of microsatellite instability (MSI) and response to cancer therapy [5]. Furthermore, their role in cancer drug resistance/response has been widely studied in several malignancies, including CRC [6][7][8].…”

Bringing to Light the Importance of the miRNA Methylome in Colorectal Cancer Prognosis Through Electrochemical Bioplatforms

“…Recently, biomarkers associated with the epigenome of tumors have gained more attention. − Among these, microRNAs (miRNAs) are becoming increasingly important epigenetic biomarkers. These small (18–24 nucleotides (nts)), single-stranded, noncoding RNAs play critical roles in a variety of cellular processes, including apoptosis, cell cycle, proliferation, differentiation, and angiogenesis, by simultaneously regulating the expression levels of several genes.…”

“…Many studies in CRC have revealed that miRNAs may function as oncogenes or tumor suppressors and play a key role in tumorigenesis, and their markedly changing expression profiles between normal and tumor tissues may be associated with metastatic processes and drug resistance. The miRNAs thus continue to gain prominence as biomarkers with great diagnostic, prognostic, and therapeutic potential. ,, …”

“…The miRNAs thus continue to gain prominence as biomarkers with great diagnostic, prognostic, and therapeutic potential. 1,3,5 Furthermore, N 6 -methyladenosine (m6A) in RNA, considered the most abundant RNA methylation (∼50% of total methylated ribonucleotides), is a dynamic and reversible modification mediated by writer (m6A-methyltransferases), removed by eraser (demethylases), and recognized by reader (m6A-binding) proteins. 6−8 The m6A RNA methylation is widely found in mRNAs and long noncoding RNAs (lncRNAs), and recent evidence suggests its role in variety of cancers, including CRC development, carcinogenesis, progression, and therapeutics.…”

“…The miRNAs thus continue to gain prominence as biomarkers with great diagnostic, prognostic, and therapeutic potential. 1 , 3 , 5 …”