miR-145 restoration overcomes oxaliplatin resistance via ABCC1 in colorectal cancer
Makaleler > Tam Makale · 2026
Yazarlar: Mahsa Sadeghzadeh, Milad Asadi, Behzad Baradaran, Venus Zafari, Soghra Bornehdeli, Haniye Mohammad Reza Khani, Behzad Mansoori, Habib Zarredar, Dariush Shanehbandi
Journal of the Egyptian National Cancer Institute, Uluslararası, Scopus, 2026, cilt 38
DOI: 10.1186/s43046-026-00349-8
Özet
BACKGROUND: Drug resistance limits effectiveness of chemotherapy in colorectal cancer (CRC). Consequently, finding appropriate strategies for re-sensitizing chemo-resistant cells is crucial. Our present study aimed at taking advantage of chemotherapy and gene therapy by restoring microRNA-145 expression in oxaliplatin resistant CRC cells. METHODS: Bioinformatic analysis of clinical CRC datasets demonstrated significantly reduced miR-145 expression in tumor tissues compared with normal samples. Oxaliplatin-resistant SW-480 cells were generated and transfected with a pCMV-miR-145 expression vector. The MTT assay was used to assess cell viability following miR-145 restoration, oxaliplatin treatment, or their combination. Apoptosis was measured via flow cytometry. Gene expression levels of ABCC1, MDR1, K-RAS, MMP-13, Bcl-2, CASP3, CASP8, and CASP9 were analyzed using qRT-PCR, and ABCC1 protein expression was evaluated by western blotting. Cell migration was assessed using a wound-healing assay. RESULTS: Co-treatment with miR-145 and Oxaliplatin significantly reduced cell viability, proliferation, and migration and increased apoptosis compared to the either treatments. Restoring miR-145 expression downregulated reduced the drug-resistance genes ABCC1 and MDR1, and reduced decreased expression of oncogenes including K-RAS and Bcl-2, while increasing expression of apoptosis-related genes (CASP3, CASP8, and CASP9). CONCLUSION: miR-145 restoration via decreasing the drug resistance biomarkers ABBCC1 and MDR1, along with other oncogenes like K-Ras and Bcl2, and increasing apoptosis conductors could sensitize oxaliplatin-resistant cells to chemotherapy. This proposes a novel and clinically translatable strategy to control drug resistance in CRC, finding new ways to increasing chemotherapeutic efficacy.