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Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
MicroRNA Assisted Gene Regulation in Colorectal Cancer
Adewale O Fadaka1, Ashley Pretorius2, Ashwil Klein3
1Department of Biotechnology, Faculty of Natural Sciences, University of the Western Cape, Private Bag X17, Bellville, 7535 Cape Town, South Africa. afadaka@uwc.ac.za.
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.
Insights
This study identifies five microRNAs crucial for gene silencing in colorectal cancer (CRC). Computational analysis reveals their strong binding affinity, offering insights into molecular mechanisms for improved CRC diagnosis and treatment.
Area of Science:
- Molecular Biology
- Genetics
- Bioinformatics
Background:
- Colorectal cancer (CRC) is a leading cause of cancer mortality, with most cases diagnosed at advanced, metastatic stages.
- Gene regulation by small non-coding RNAs, like microRNAs, is critical in cancer development and progression.
- Understanding microRNA-mediated gene silencing mechanisms in CRC is essential for advancing diagnostics and therapeutics.
Purpose of the Study:
- To predict the molecular mechanisms of gene regulation via microRNA-mRNA interactions in colorectal cancer.
- To identify key microRNAs involved in the gene silencing pathways relevant to CRC.
Main Methods:
- In silico identification of five candidate microRNAs targeting genes implicated in CRC.
- Utilized databases (miRTarBase, gbCRC, CoReCG, DAVID) for target prediction, correlation, and prioritization.
- Employed molecular docking (PATCHDOCK) and visualization tools (Schrödinger, Discovery Studio) to analyze microRNA-mRNA-protein interactions.
Main Results:
- Five candidate microRNAs demonstrated significant binding affinity to their predicted mRNA targets.
- Computational analysis confirmed the potential of these microRNAs to regulate gene expression through silencing mechanisms.
- Molecular docking provided insights into the specific interactions between microRNAs, mRNA, and argonaute proteins.
Conclusions:
- The identified microRNAs play a crucial role in the gene silencing mechanism within colorectal cancer.
- This research elucidates microRNA-based gene regulation, paving the way for novel diagnostic and therapeutic strategies for CRC.
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