MicroRNA‑361‑5p induces hepatocellular carcinoma cell apoptosis and enhances drug sensitivity by targeting MAP3K9

Ren,Qingbo; Xiao,Xiangmei; Leng,Xiaoqian; Zhang,Qi; Zhou,Xue; Ren,Ziyuan; Xiao,Hang

doi:10.3892/etm.2021.10006

MicroRNA‑361‑5p induces hepatocellular carcinoma cell apoptosis and enhances drug sensitivity by targeting MAP3K9

Authors:
- Qingbo Ren
- Xiangmei Xiao
- Xiaoqian Leng
- Qi Zhang
- Xue Zhou
- Ziyuan Ren
- Hang Xiao
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Affiliations: Department of Clinical Laboratory, Qingdao Sixth People's Hospital, Qingdao, Shandong 266033, P.R. China, Department of Clinical Laboratory, Qingdao Fifth People's Hospital, Qingdao, Shandong 266000, P.R. China, Medical College of Cheeloo, Shandong University, Qingdao, Shandong 266000, P.R. China, Department of General Internal Medicine, Qingdao Sixth People's Hospital, Qingdao, Shandong 266033, P.R. China
Published online on: March 31, 2021 https://doi.org/10.3892/etm.2021.10006
Article Number: 574
Copyright: © Ren et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNAs (miRs) participate in the development of several cancers. miR‑361‑5p suppresses the proliferation of hepatocellular carcinoma (HCC) cells. However, its function and potential underlying mechanism of action in the chemoresistance of HCC remains unknown. Therefore, cisplatin (DDP)‑resistant HCC cells were used to study the role and potential mechanism of action of miR‑361‑5p in HCC resistance to chemotherapy. TargetScan software and dual‑luciferase reporter assays were used to determine whether MAPK kinase kinase 9 (MAP3K9) is a target gene of miR‑361‑5p. Subsequently, reverse transcription‑quantitative PCR and western blot analyses demonstrated that miR‑361‑5p mimic decreased MAP3K9 expression levels in Huh7 cells and this change was reversed by transfection with the MAP3K9‑plasmid. In addition, compared with THLE‑2 cells, miR‑361‑5p was downregulated, while MAP3K9 was upregulated in Huh7 cells. MAP3K9 also reversed the miR‑361‑5p‑induced HCC cell apoptosis. A DDP‑resistant cell line, Huh7/DDP, was established and MTT analysis revealed that the IC₅₀ value of DDP treatment in Huh7/DDP cells was higher compared with that in Huh7 cells. miR‑361‑5p expression was lower in Huh7/DDP cells compared with that in Huh7 cells. Similarly, miR‑361‑5p downregulated the expression levels of MAP3K9 in Huh7/DDP cells. Furthermore, MAP3K9 reversed miR‑361‑5p‑induced sensitivity of Huh7/DDP cells to DDP and miR‑361‑5p induced Huh7/DDP cell apoptosis. Therefore, the findings of the present study demonstrated that the miR‑361‑5p/MAP3K9 axis may serve as a new potential biomarker and therapeutic target for DDP‑resistant HCC.

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