title: 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.
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. Electronic address: zhaosong0099@sina.com.
authors.forename: Song
authors.initials: S
authors.lastname: Zhao
mesh_terms: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D002945:Cisplatin; D035683:MicroRNAs; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C421142:ABCC10 protein, human; C414431:BAG3 protein, human; C487931:mirnlet7 microRNA, human
keywords: ABCC10; Bcl2-associated athanogene 3 (BAG3); Esophageal carcinoma; miR-let-7g; miR-let-7i