Invasive Breast Cancer: miR-24-2 Targets Genes Associated with Survival and Sensitizes MDA-MB-231 Cells to Berberine.

Abstract

MicroRNA aberrations including that of miR-24-2 have been reported in various cancers. However, the target genes for miR-24-2 are yet to be identified and validated in invasive breast cancer and the triple-negative breast cancer (TNBC). Using in silico approaches and gene expression analyses, we identified and validated the target genes of miR-24-2 in invasive breast cancer, majority of which were TNBC. We studied the translational potential of these target genes using berberine in a TNBC cell line. Differentially expressed genes targeted by miR-24-2 were identified and analyzed for their survival effects using the The Cancer Genome Atlas-Breast Invasive Carcinoma (-BRCA) samples. Furthermore, we carried out protein-protein interaction, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene expression, and Kaplan-Meier survival analyses using common targets of miR-24-2 in invasive breast cancer/TNBC. We identified 11 biomarker candidate genes as crucial targets of miR-24-2. The survival of breast cancer patients was significantly associated with the low expressions of nine genes, including RACGAP1, KIAA1199, TIMM17A, LYRM7, IL1R1, SLC1A3, DTX4, L1CAM, and SAP30-like (SAP30L), and high expressions of two genes, SOD2 and HLA-DQB2. These in silico findings were validated by overexpressing miR-24-2 and assessing the expression pattern of these target genes in the TNBC MDA-MB-231 cells. miR-24-2 overexpression inhibited (by 20%; p < 0.001) cell proliferation and sensitized the anticancer effect of berberine. In all, this study reports on the novel target genes of miR-24-2 in invasive breast cancer/TNBC, and that miR-24-2 sensitizes MDA-MB-231 cells to berberine. These data lend evidence for the translational potentials of miR-24-2 for invasive breast cancer diagnostic and therapeutic innovation.

• Authors: Mansoor Ali, Rameshwar N K Bamezai, Rana P Singh
• Journal: Omics : a journal of integrative biology (OMICS) Vol. 27 Issue 9 Pg. 409-420 (09 2023) ISSN: 1557-8100 [Electronic] United States
• PMID: 37669117 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Berberine
• MicroRNAs
• LYRM7 protein, human
• Molecular Chaperones
• Mitochondrial Proteins
• MIRN24 microRNA, human

Topics

• Humans
• Triple Negative Breast Neoplasms (drug therapy, genetics)
• Berberine (pharmacology)
• MDA-MB-231 Cells
• MicroRNAs (genetics)
• Cell Line
• Molecular Chaperones
• Mitochondrial Proteins