Identification of Novel miRNAs, Targeting Genes, Signaling Pathway, and the Small Molecule for Overcoming Oxaliplatin Resistance of Metastatic Colorectal Cancer.

Autor: Misbah M; International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan., Kumar M; Centre for Translational and Clinical Research, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India., Lee KH; Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.; PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.; Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11031, Taiwan., Shen SC; International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.; Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
Jazyk: angličtina
Zdroj: BioMed research international [Biomed Res Int] 2022 Sep 19; Vol. 2022, pp. 3825760. Date of Electronic Publication: 2022 Sep 19 (Print Publication: 2022).
DOI: 10.1155/2022/3825760
Abstrakt: One of the globally common cancers is colorectal cancer (CRC). At present, a surgical approach remains a good option for CRC patients; however, 20% of surgically treated CRC patients experience metastasis. Currently, even the first-line used drug, oxaliplatin, remains inadequate for treating metastatic CRC, and its side effect of neurotoxicity is a major problem when treating CRC. The Gene Omnibus GSE42387 database contains gene expression profiles of parental and oxaliplatin-resistant LoVo cell lines. Differentially expressed genes (DEGs) between parental and oxaliplatin-resistance LoVo cells, protein-protein interactions (PPIs), and a pathway analysis were determined to identify overall biological changes by an online DAVID bioinformatics analysis. The ability of DEGs to predict overall survival (OS) and disease-free survival (DFS) was validated by the SPSS 22.0, using liver metastasis CRC patient samples of GSE41258. The bioinformatics web tools of the GEPIA, the Human Protein Atlas, WebGestalt, and TIMER platforms were used. In total, 218 DEGs were identified, among which 105 were downregulated and 113 were upregulated. After mapping the PPI networks and pathways, 60 DEGs were identified as hub genes (with high degrees). Six genes ( TGFB1 , CD36 , THBS1 , FABP1 , PCK1 , and IRS1 ) were involved with malaria, PPAR signaling, and the adipocytokine signaling pathway. High expressions of CD36 and PCK1 were associated with the poor survival of CRC patients in the GSE41258 database. We predicted specific micro (mi)RNAs that targeted the 3' untranslated region (UTR) of PCK1 by using miRWalk. It was found that three miRNAs, viz., miR-7-5p, miR-20a-3p, and miR-636, may be upstream targets of those genes. High expression levels of miR-7-5p, miR-20a-3p, and miR-636 were associated with poor OS of CRC patients, and the small-molecule compound, mersalyl, is a promising drug for treating oxaliplatin-resistant CRC. In conclusion, miR-7-5p miR-20a-3p, and miR-636 targeted the PCK1 biomarker in the PPAR signaling pathway, which is involved in oxaliplatin-resistant CRC. Meanwhile, mersalyl was identified as a potential drug for overcoming oxaliplatin resistance in CRC. Our findings may provide novel directions and strategies for CRC therapies.
Competing Interests: The authors declare that they have no known competing financial interest or personal relationship that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Md Misbah et al.)
Databáze: MEDLINE
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