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  • Title: miRNA-93-5p Promotes Gemcitabine Resistance in Pancreatic Cancer Cells by Targeting the PTEN-Mediated PI3K/Akt Signaling Pathway.
    Author: Wu Y, Xu W, Yang Y, Zhang Z.
    Journal: Ann Clin Lab Sci; 2021 May; 51(3):310-320. PubMed ID: 34162560.
    Abstract:
    OBJECTIVE: To investigate the role and potential underlying mechanism of miR-93-5p in the carcinogenesis and gemcitabine resistance of pancreatic cancer (PC) cells. METHODS: We generated a gemcitabine-resistant PC cell line Bxpc-3/GemR following prolonged gemcitabine exposure to its parental gemcitabine-sensitive counterpart Bxpc-3/Par. Cell viability was monitored by MTS assay. Transfection was performed using Lipofectamine 3000 reagent. Cell apoptosis and rhodamine 123 fluorescence were detected by flow cytometry. Luciferase activities were measured using the luciferase reporter gene assay. Expression analysis was carried out by qRT-PCR and western blot. RESULTS: Significantly increased viability and enhanced expression of the multi-drug resistance-1 (MDR1) gene were observed in Bxpc-3/GemR cells, in which miR-93-5p is considerably upregulated, compared with Bxpc-3/Par cells. Downregulation of miR-93-5p inhibited cell viability, induced cell apoptosis, and decreased MDR1 expression in Bxpc-3/GemR cells, whereas upregulation essentially reversed these properties in Bxpc-3/Par cells. We further confirmed that PTEN was a direct target of miR-93-5p, and overexpression of miR-93-5p was accompanied by a significant increase in the phosphorylation of Akt expression in the Bxpc-3/Par cells. Moreover, inhibition of PI3K/Akt signaling diminished MDR1 expression. CONCLUSION: These observations suggest that miR-93-5p modulates tumorigenesis and gemcitabine resistance in PC cells via targeting the PTEN/PI3K/Akt signaling pathway.
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