TY - JOUR
T1 - Comprehensive Analysis of microRNA Methylation Profiles and Determination of Their Functional Significance in Colorectal Cancer
T2 - A Study Protocol
AU - Ab Mutalib, Nurul Syakima
AU - Ismail, Imilia
AU - Zawawi, Muhammad Redha Abdullah
AU - Abu, Nadiah
AU - Sulaiman, Siti Aishah
AU - Tan, Loh Teng Hern
AU - Lee, Learn Han
N1 - Funding Information:
Funding: This research was funded by the Ministry of Higher Education Malaysia, grant number FRGS/1/2020/SKK0/UKM/02/11.
Publisher Copyright:
© 2023, HH Publisher. All rights reserved.
PY - 2023/1/4
Y1 - 2023/1/4
N2 - Colorectal cancer (CRC) is a leading cause of cancer-associated fatalities globally. Despite the notable progress in diagnostics and patient care, challenges persist in areas such as early detection, prognostic variable identification, metastatic disease treatment, and personalised treatment options. In CRC, microRNAs, a type of short non-coding RNA, are found to be deregulated and can significantly influence its onset and progression. However, previous microRNA research primarily focused on expression levels to ascertain their biological significance, leaving the microRNA methylation landscapes in CRC patients largely unexplored. This study aims to investigate the genome-wide methylome profiles of microRNA and clarify their roles in CRC. We will analyse the microRNA methylation profiles from our in-house data of more than 100 CRCs and correlate the differentially methylated microRNAs with clinicopathological features. To understand the biological significance of methylated microRNAs, we will perform pathway enrichment analysis and molecular dynamics simulations to examine the binding of argonaut protein to the differentially methylated microRNAs and the structural changes involved. Furthermore, we will conduct functional studies to determine the roles of selected microRNAs. CRC cell lines with hypermethylated microRNA of interest will be treated with a demethylating agent, followed by cell-based assays. Subsequent transcriptome-wide microRNA gene target identification and protein profiling will be performed to interrogate the molecular pathways affected by demethylation of the microRNA of interest. Methylation signifies a major transformation in cancer detection, as widespread epigenetic changes could potentially provide superior early-stage cancer detection and classification compared to somatic mutations. Effective CRC diagnosis ensures timely and appropriate treatment for patients, thereby improving their quality of life. The insights gained from this study could be applied to individualized health diagnostics, disease prognostication, and treatment monitoring.
AB - Colorectal cancer (CRC) is a leading cause of cancer-associated fatalities globally. Despite the notable progress in diagnostics and patient care, challenges persist in areas such as early detection, prognostic variable identification, metastatic disease treatment, and personalised treatment options. In CRC, microRNAs, a type of short non-coding RNA, are found to be deregulated and can significantly influence its onset and progression. However, previous microRNA research primarily focused on expression levels to ascertain their biological significance, leaving the microRNA methylation landscapes in CRC patients largely unexplored. This study aims to investigate the genome-wide methylome profiles of microRNA and clarify their roles in CRC. We will analyse the microRNA methylation profiles from our in-house data of more than 100 CRCs and correlate the differentially methylated microRNAs with clinicopathological features. To understand the biological significance of methylated microRNAs, we will perform pathway enrichment analysis and molecular dynamics simulations to examine the binding of argonaut protein to the differentially methylated microRNAs and the structural changes involved. Furthermore, we will conduct functional studies to determine the roles of selected microRNAs. CRC cell lines with hypermethylated microRNA of interest will be treated with a demethylating agent, followed by cell-based assays. Subsequent transcriptome-wide microRNA gene target identification and protein profiling will be performed to interrogate the molecular pathways affected by demethylation of the microRNA of interest. Methylation signifies a major transformation in cancer detection, as widespread epigenetic changes could potentially provide superior early-stage cancer detection and classification compared to somatic mutations. Effective CRC diagnosis ensures timely and appropriate treatment for patients, thereby improving their quality of life. The insights gained from this study could be applied to individualized health diagnostics, disease prognostication, and treatment monitoring.
KW - Colorectal cancer
KW - differential methylation
KW - methylation profiles
KW - microRNAs
KW - personalized health diagnostics
KW - precision medicine
KW - SDG 3 Good health and well-being
UR - http://www.scopus.com/inward/record.url?scp=85180509642&partnerID=8YFLogxK
U2 - 10.36877/pmmb.a0000389
DO - 10.36877/pmmb.a0000389
M3 - Article
AN - SCOPUS:85180509642
SN - 2637-1049
VL - 6
JO - Progress in Microbes and Molecular Biology
JF - Progress in Microbes and Molecular Biology
IS - 1
M1 - a0000389
ER -
