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Hailong Mi,* Xiaochun Wang,* Fang Wang, Lin Li, Mingzhi Zhu, Nan Wang, Youyi Xiong, Yuanting Gu Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 475000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuanting GuDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou 450000, Henan Province, People’s Republic of ChinaTel +86-0371-67967172Email guytzzdx0705@126.comBackground: Increasing evidence implies the participation of long non-coding RNAs (lncRNAs) in chemoresistance to cancer treatment. Their role and molecular mechanisms in breast cancer chemoresistance, nevertheless, are yet not considerably elucidated. In this work, we research the function of small nucleolar RNA host gene 15 (SNHG15) in cisplatin (DDP) resistance of breast cancer and uncover the underlying molecular mechanism.Methods: SNHG15 and miR-381 expression levels were detected using Quantitative real-time PCR (qRT-PCR) analysis. The functional roles of SNHG15 and miR-381 in breast cancer were determined using MTT assay and flow cytometry analysis. The effect of SNHG15 on miR-381 expression was determined using Luciferase reporter assay, RNA immunoprecipitation (RIP) assay and qRT-PCR analysis.Results: SNHG15 was found to be up-regulated in cisplatin resistant breast cancer tissues and cell lines. Breast cancer patients with high SNHG15 expression had a poor prognosis. SNHG15 silencing enhanced cisplatin sensitivity of MCF-7/DDP and MDA-MB-231/DDP cells. Additionally, SNHG15 could function as a miR-381 sponge. miR-381 overexpression could overcome cisplatin resistance. miR-381 knockdown countered SNHG15 knockdown-mediated enhancement of cisplatin sensitivity in MCF-7/DDP and MDA-MB-231/DDP cells. Besides, SNHG15 knockdown facilitated cisplatin sensitivity of cisplatin resistant breast cancer cells in vivo.Conclusion: In summary, SNHG15 knockdown overcame cisplatin resistance of breast cancer by sponging miR-381, providing a novel therapeutic target for breast cancer.Keywords: breast cancer, cisplatin, small nucleolar RNA host gene 15, miR-381 |