MicroRNA Assisted Gene Regulation in Colorectal Cancer

Abstract

Colorectal cancer (CRC) is the second-leading cause of cancer death and a major public health problem. Nearly 80% CRC cases are diagnosed after the disease have metastasized and are often too advanced for treatment. Small non-coding RNA guides argonaute protein to their specific target for regulation as the sole of RNA induced silencing complex for gene silencing. These non-coding RNA for example microRNA, are thought to play a key role in affecting the efficiency of gene regulation in cancer, especially CRC. Understanding the mechanism at the molecular level could lead to improved diagnosis, treatment, and management decisions for CRC. The study aimed to predict the molecular mechanism of gene regulation based microRNA-mRNA duplex as a lead in the silencing mechanism. Five candidate microRNAs were identified through the in silico approach. The MicroRNA target prediction and subsequent correlation, and prioritization were performed using miRTarBase, gbCRC and CoReCG, and DAVID databases respectively. Protein selection and preparation were carried out using PDB and Schrödinger suits. The molecular docking analysis was performed using PATCHDOCK webserver and visualized by discovery studio visualizer. The results of the study reveal that the candidate microRNAs have strong binding affinity towards their targets suggesting a crucial factor in the silencing mechanism. Furthermore, the molecular docking of the receptor to both the microRNA and microRNA-mRNA duplex were analyzed computationally to understand their interaction at the molecular level. Conclusively, the study provides an explanation for understanding the microRNAs-based gene regulation (silencing mechanism) in CRC.

Gene Expression Alterations and Molecular Analysis of CHEK1 in Solid Tumors

“…Various mechanisms involved in the regulation of CHEK1 expression and activation were previously described [53][54][55]. It can also be regulated at the post-transcriptional level by microRNAs [23,56], which are key regulators of tumor growth and response to treatment [57]. The expression of CHEK1 was further validated, and demonstrated that the CHEK1 gene may possess either oncogenic or anti-oncogenic characteristics, depending on the type of cancer.…”

“…The modified method of our previous analysis [56] was employed to investigate the mechanism of action of CHEK1-miR-195 and human argonaute protein in solid tumors. Schrodinger suit, MiRTarBase, Discovery Studio Visualizer (v19.1.0.18287), PROCHECK, PATCHDOCK, RNAfold, and RNA-composer software were all used in this analysis.…”

Genomic profiling of microRNA target genes in colorectal cancer

“…The microRNA target genes were used as dataset due to the significance of the associated microRNAs from our previous study (hsa-miR-513b-3p, hsa-miR-500b-3p, hsa-miR-500a-3p, hsa-miR-450b-3p, hsa-miR-193a-5p) along their validated microRNAs hsa-miR-193a-5p, hsa-miR-450b-3p, hsa-miR-501-3p, hsa-miR-501-3p, and hsa-miR-513a-3p). 8 After the assignment of function and the determination of the mechanism of action to these microRNAs and target genes (previous studies), 15,16,23 their genomic profiling deserves closer attention in CRC.…”

“…In this study, two datasets were queried using the cBioPortal, with the first dataset being the differentially expressed microRNA target genes from our previous in silico studies. 8,15,16 Seven of the genes targeted by our candidate microRNAs that showed significance (Figure 1) were profiled and their expression in CRC was further evaluated. The Colorectal Adenocarcinoma in The Cancer Genome Atlas (TCGA) Colorectal Cancer project (TCGA, Nature 2012) consisting of the whole-exome sequencing in colorectal carcinoma tumor/normal pairs was used as the second dataset.…”

MicroRNA-based regulation of Aurora A kinase in breast cancer

“…The molecular docking analysis of AURKA and microRNA of interest was performed by Schrodinger suite, PATCHDOCK, and Discovery Studio Visualizer (DSV) following the approach described by Fadaka et al [90].…”