Int J Biol Sci 2020; 16(5):827-837. doi:10.7150/ijbs.32460

Research Paper

Overexpression of microRNA-9 enhances cisplatin sensitivity in hepatocellular carcinoma by regulating EIF5A2-mediated epithelial-mesenchymal transition

Ying Bao1*, Yibo Zhang2*, Yongliang Lu3*, Huihui Guo1*, Zhaohuo Dong1, Qiuqiang Chen1, Xilin Zhang1, Weiyun Shen1, Wei Chen4,5✉, Xiang Wang1✉

1. Key Laboratory for Translational Medicine, First Affiliated Hospital, Huzhou University, the First People's Hospital of Huzhou, huzhou 313000,China
2. Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China
3. Department of medicine,Huzhou University, huzhou 313000,China
4. Cancer Institute of Integrated traditional Chinese and Western Medicine, Key laboratory of cancer prevention and therapy combining traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang, 310012, China
5. Department of Medical Oncology, Tongde hospital of Zhejiang Province, Hangzhou, Zhejiang, 310012, China
* Contributed equally to this work

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Citation:
Bao Y, Zhang Y, Lu Y, Guo H, Dong Z, Chen Q, Zhang X, Shen W, Chen W, Wang X. Overexpression of microRNA-9 enhances cisplatin sensitivity in hepatocellular carcinoma by regulating EIF5A2-mediated epithelial-mesenchymal transition. Int J Biol Sci 2020; 16(5):827-837. doi:10.7150/ijbs.32460. Available from http://www.ijbs.com/v16p0827.htm

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Abstract

We investigated the role of microRNA (miR)-9 in modulating chemoresistance in hepatocellular carcinoma (HCC) cells. MiR-9 was overexpressed or knocked down in HCC cell lines. Cell viability, cell proliferation, the expression of EIF5A2 and the epithelial-mesenchymal transition (EMT)-related proteins were examined. HCC cells overexpressing miR-9 were more sensitive to cisplatin; miR-9 knockdown yielded the opposite result. The in vivo nude mouse HCC xenograft tumors yielded the same results. EIF5A2 was identified as a potential target of miR-9, where miR-9 regulated EIF5A2 expression at mRNA and protein level. EIF5A2 knockdown reversed miR-9 inhibition-mediated cisplatin resistance. Altering miR-9 and EIF5A2 expression changed E-cadherin and vimentin expression. Furthermore, EIF5A2 mediated miR-9 EMT pathway regulation, indicating that miR-9 can enhance cisplatin sensitivity by targeting EIF5A2 and inhibiting the EMT pathway. Targeting miR-9 may be useful for overcoming drug resistance in HCC.

Keywords: miR-9, EIF5A2, chemoresistance, epithelial-mesenchymal transition