RNA-Interference-Mediated miR-122-Based Gene Regulation in Colon Cancer, a Structural In Silico AnalysisShow others and affiliations
2022 (English)In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 23, article id 15257
Article in journal (Refereed) Published
Abstract [en]
The role of microRNA 122 (miR-122) in colorectal cancer (CRC) has not been widely investigated. In the current study, we aimed to identify the prominent gene and protein interactors of miR122 in CRC. Based on their binding affinity, these targets were chosen as candidate genes for the creation of miR122-mRNA duplexes. Following this, we examined the miRNA-mediated silencing mechanism using the gene-silencing complex protein Argonaute (AGO). Public databases, STRING, and GeneMANIA were utilized to identify major proteins and genes interacting with miR-122. DAVID, PANTHER, UniProt, FunRich, miRwalk, and KEGG were used for functional annotation, pathway enrichment, binding affinity analysis, and expression of genes in different stages of cancer. Three-dimensional duplexes of hub genes and miR-122 were created using the RNA composer, followed by molecular interaction analysis using molecular docking with the AGO protein. We analyzed, classified, and scrutinized 93 miR-122 interactors using various bioinformatic approaches. A total of 14 hub genes were categorized as major interactors of miR-122. The study confirmed the role of various experimentally documented miR-122 interactors such as MTDH (Q86UE4), AKT1 (P31749), PTPN1 (P18031), MYC (P01106), GSK3B (P49841), RHOA (P61586), and PIK3CG (P48736) and put forth several novel interactors, with AKT3 (Q9Y243), NCOR2 (Q9Y618), PIK3R2 (O00459), SMAD4 (P61586), and TGFBR1 (P36897). Double-stranded RNA duplexes of the strongest interactors were found to exhibit higher binding affinity with AGO. In conclusions, the study has explored the role of miR-122 in CRC and has identified a closely related group of genes influencing the prognosis of CRC in multiple ways. Further, these genes prove to be targets of gene silencing through RNA interference and might serve as effective therapeutic targets in understanding and treating CRC.
Place, publisher, year, edition, pages
MDPI, 2022. Vol. 23, no 23, article id 15257
Keywords [en]
Argonaute protein, RNA interference, colorectal cancer, gene silencing, miR-122, network biology, signaling pathways
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:oru:diva-102650DOI: 10.3390/ijms232315257ISI: 000897416800001PubMedID: 36499586Scopus ID: 2-s2.0-85143801229OAI: oai:DiVA.org:oru-102650DiVA, id: diva2:1718299
Funder
Swedish Cancer Society, 19 0322 Pj
Note
Funding agency:
Department of Science & Technology (India)
Department of Science & Technology (DOST), Philippines EMR/2017/001877
2022-12-122022-12-122024-03-05Bibliographically approved