BAG3-mediated miRNA let-7g and let-7i inhibit proliferation and enhance apoptosis of human esophageal carcinoma cells by targeting the drug transporter ABCC10

Abstract

Cisplatin (diamminedichloroplatinum, DDP) is widely used as the first-line treatment for patients with unresectable or no metastatic cancer. However, the appearance of DDP resistance frequently occurred in the treatment of cancers, including esophageal carcinoma (EC). The purposes of this study are to determine the antitumor effects of miR-let-7g/i (let–7g/i) on EC cells and to investigate whether let-7g and let-7i have a relationship with the drug resistance gene ABCC10 on EC cells. qRT-PCR and western blot analysis demonstrated that Bcl2-associated athanogene 3 (BAG3) and miR-let-7g/i have the opposite expression levels in primary esophageal squamous cell carcinoma tissues and EC cell lines. Overexpression of miR-let-7g/i significantly inhibited the cell proliferation and promoted DDP-induced apoptosis of EC109 and TE10 cells. Finally, ABCC10, a drug resistance gene, was identified as a functional and direct target gene of miR-let-7g/i. Luciferase reporter assay confirmed that let-7g and let-7i combined directly with 3′UTR of ABCC10, in consequence, inhibiting ABCC10 expression and enhancing cellular sensitivity to drugs. This study provides the first demonstration that miR-let-7g/i target ABCC10 and modulate DDP resistance in EC cell lines.