Inhibitory effect of miR-140-5p on doxorubicin resistance of hepatocellular carcinoma

Gao,Xiaojie; Jiang,Yan; Li,Yingying

doi:10.3892/etm.2021.9938

Inhibitory effect of miR-140-5p on doxorubicin resistance of hepatocellular carcinoma

Authors:
- Xiaojie Gao
- Yan Jiang
- Yingying Li
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Affiliations: Department of Pharmacy, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou Zhejiang 310005, P.R. China, Department of Pharmacy, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China
Published online on: March 18, 2021 https://doi.org/10.3892/etm.2021.9938
Article Number: 507
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

To investigate the role of microRNA (miR)-140-5p in doxorubicin (DOX) sensitivity in hepatocellular carcinoma, miR-140-5p and peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) expression was first evaluated in hepatocellular carcinoma tissues using starBase. Next, in vitro experiments were performed. Cell line expression of miR-140-5p and PIN1 expression was detected by reverse transcription polymerase chain reaction. Cell viability and proliferation were determined by the Cell Counting Kit-8 and EdU assays. The relationship between miR-140-5p and PIN1 was evaluated by TargetScan and a luciferase reporter system. Western blotting was used to detect the expression of PIN1. It was observed that miR-140-5p was downregulated in hepatocellular carcinoma tissues and cell lines compared with normal samples in HCC or normal liver cells. Gain-of-function experiments revealed that miR-140-5p mimics were able to enhance DOX sensitivity of hepatocellular carcinoma cells. Further studies revealed that PIN1 was a target gene of miR‑140-5p. Suppression of PIN1 led to higher DOX sensitivity in hepatocellular carcinoma cells. Finally, when comparing a PIN1-siRNA alone group and a PIN1-siRNA plus miR-140-5p inhibitor group, there was no significant difference in cell viability. Furthermore, miR-140-5p mimics did not reduce the sensitivity of PIN1mut plasmid to DOX in HUH7 and SNU449 cells. The present study demonstrated that miR-140-5p could enhance DOX sensitivity in hepatocellular carcinoma cells by targeting PIN1.

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