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MicroRNA Assisted Gene Regulation in Colorectal Cancer

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 regulatio...

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Autores principales: Fadaka, Adewale O., Pretorius, Ashley, Klein, Ashwil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801675/
https://www.ncbi.nlm.nih.gov/pubmed/31623294
http://dx.doi.org/10.3390/ijms20194899
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author Fadaka, Adewale O.
Pretorius, Ashley
Klein, Ashwil
author_facet Fadaka, Adewale O.
Pretorius, Ashley
Klein, Ashwil
author_sort Fadaka, Adewale O.
collection PubMed
description 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.
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spelling pubmed-68016752019-10-31 MicroRNA Assisted Gene Regulation in Colorectal Cancer Fadaka, Adewale O. Pretorius, Ashley Klein, Ashwil Int J Mol Sci Article 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. MDPI 2019-10-03 /pmc/articles/PMC6801675/ /pubmed/31623294 http://dx.doi.org/10.3390/ijms20194899 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fadaka, Adewale O.
Pretorius, Ashley
Klein, Ashwil
MicroRNA Assisted Gene Regulation in Colorectal Cancer
title MicroRNA Assisted Gene Regulation in Colorectal Cancer
title_full MicroRNA Assisted Gene Regulation in Colorectal Cancer
title_fullStr MicroRNA Assisted Gene Regulation in Colorectal Cancer
title_full_unstemmed MicroRNA Assisted Gene Regulation in Colorectal Cancer
title_short MicroRNA Assisted Gene Regulation in Colorectal Cancer
title_sort microrna assisted gene regulation in colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801675/
https://www.ncbi.nlm.nih.gov/pubmed/31623294
http://dx.doi.org/10.3390/ijms20194899
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