Let-7b attenuates cisplatin resistance and tumor growth in gastric cancer by targeting AURKB. (December 2018)

• Record Type: Journal Article
• Authors: Han, Xiao; Zhang, Jing-Jing; Han, Zheng-Quan; Zhang, Hai-Bin; Wang, Zi-An
• Is Part Of: Cancer gene therapy. Volume 25:Number 11/12(2018)
• Page Start: 300
• Page End: 308
• Publication Date: 2018-12
• Subjects: Cancer -- Gene therapy -- Periodicals; Gene therapy -- Periodicals; Gene Therapy -- Periodicals; Neoplasms -- therapy -- Periodicals; Electronic journals; 616.99406
• DOI: 10.1038/s41417-018-0048-8
• Languages: English
• ISSNs: 0929-1903

Abstract

Abstract Platinum-based chemotherapy is currently a standard treatment strategy for patients with gastric cancer. Eventhough it has been widely shown that microRNAs (miRNAs) are involved in tumor development, whether miRNAs have a role in chemosensitivity of gastric cancer cells to platinum-based treatment remain largely undefined. In this study, a cisplatin-resistant gastric cancer cell line (SGC7901/DDP) with stable enhanced expression or knockdown of let-7b was generated. MTT and TUNEL assays were carried out to assess whether miR-let-7 is crucial for cell viability and apoptosis, respectively. In vitro luciferase reporter assay was performed to explore target genes of let-7b. Further, a subcutaneously transplanted tumor model in BALB/c nude mice was used to determine the impacts of let-7b on tumor growth in vivo. We observed that the let-7b-expression level of SGC7901/DDP cells was significantly lower than for its parental SGC7901 cells. Transfection of let-7b mimics was found to increase the cytotoxicity of DDP to SGC7901/DDP cells by inducing apoptosis. However, reversed cytotoxicity of DDP was observed in SGC7901/DDP cells with knockdown of let-7b. Luciferase reporter assay indicated that let-7b targetedAURKB in SGC7901/DDP cells. Knockdown ofAURKB imitated the effect of let-7b overexpression on the sensitivity of SGC7901/DDP cells to DDP. Further investigation demonstrated that the SGC7901/DDP primary tumor growth was significantly reduced by let-7b mimic transfection. These findings indicate that overexpression of let-7b might provide a potential strategic approach for attenuating DDP resistance in SGC7901/DDP human gastric cancer cells.