MicroRNA Assisted Gene Regulation in Colorectal Cancer.

Adewale Fadaka,Ashwil Klein,Ashley Pretorius

doi:10.3390/ijms20194899

Adewale Fadaka, Ashwil Klein + Show 1 more

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https://doi.org/10.3390/ijms20194899

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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.

Highlights

Colorectal cancer (CRC) is considered as one of the most threatening diseases due to its incidence and mortality rate worldwide [1], and the most frequent cancers in western world [2]
The sequence similarity search was employed through the basic local alignment search tool for nucleic acids (BLASTN) and the Homology Detection and Clustering Database at High Identity with Tolerance (CH-HIT-EST-2D) between the total microRNAs from miRBase as reference microRNAs and microRNAs experimentally validated in 4 databases (DbDEMC at http://www.picb.ac.cn/dbDEMC/, miR2Disease at http://www. mir2disease.org/, HMDD at http://www.cuilab.cn/hmdd, and miRCancer at http://mircancer.ecu.edu/)
With a similarity threshold of 0.90, the result was text-mined to obtain the final list of 5 candidate microRNAs together with their clusters associated with CRC (Table 1)

Summary

Introduction

Colorectal cancer (CRC) is considered as one of the most threatening diseases due to its incidence and mortality rate worldwide [1], and the most frequent cancers in western world [2]. It is imperative to elucidate the mechanism of gene silencing in the tumorigenesis of CRC for better understanding. The interactions between protein and nucleic acids play essential roles in various cellular and biological processes, including DNA replication, RNA transcription, the translation of polypeptides, RNA splicing, and the degradation of nucleic acids [6,7]. RNA binding proteins are mediators of RNA silencing processes, such as pathways in microRNA and RNA interference. The RISC complexed with AGO employs small molecules, such as microRNA, as a guide for target recognition and silencing through translational repression and/or degradation [11]

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