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Let-7b attenuates cisplatin resistance and tumor growth in gastric cancer by targeting AURKB

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A Correction to this article was published on 21 November 2018

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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 targeted AURKB in SGC7901/DDP cells. Knockdown of AURKB 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.

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  • 21 November 2018

    The original version of this Article neglected to indicate that the study was supported by Anhui Natural Science Foundation Project (1608085MH201). This has now been corrected in both the PDF and HTML versions of the Article.

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Funding

The study was supported by Anhui Natural Science Foundation Project (1608085MH201).

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Correspondence to Zi-An Wang.

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Han, X., Zhang, JJ., Han, ZQ. et al. Let-7b attenuates cisplatin resistance and tumor growth in gastric cancer by targeting AURKB. Cancer Gene Ther 25, 300–308 (2018). https://doi.org/10.1038/s41417-018-0048-8

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