MicroRNA‑212‑3p inhibits paclitaxel resistance through regulating epithelial‑mesenchymal transition, migration and invasion by targeting ZEB2 in human hepatocellular carcinoma

Yang,Jianyu; Cui,Ronghua; Liu,Yingke

doi:10.3892/ol.2020.11884

MicroRNA‑212‑3p inhibits paclitaxel resistance through regulating epithelial‑mesenchymal transition, migration and invasion by targeting ZEB2 in human hepatocellular carcinoma

Authors:
- Jianyu Yang
- Ronghua Cui
- Yingke Liu
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Affiliations: Workshop of National TCM Master, Sun Guangrong, The Harmonizing School of TCM, Beijing University of Chinese Medicine, Haikou, Hainan 570208, P.R. China, Department of Oncology, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, Hainan 570208, P.R. China, Department of Pediatrics, Beijing Hepingli Hospital, Beijing 100013, P.R. China
Published online on: July 16, 2020 https://doi.org/10.3892/ol.2020.11884
Article Number: 23
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatocellular carcinoma (HCC) is one of the most common tumor malignances with poor chemotherapeutic efficiency due to chemoresistance. MicroRNAs (miRNAs) have essential roles in regulating chemoresistance. However, the mechanism underlying the involvement of miR‑212‑3p in paclitaxel (PTX) resistance in HCC remains unclear. PTX resistance was investigated in the present study by assessing cell viability, the half maximal inhibitory concentration of PTX, resistance‑associated protein levels and apoptosis. The expression levels of miR‑212‑3p and zinc finger E‑box binding homeobox 2 (ZEB2) were detected by reverse transcription‑quantitative PCR and western blotting. The epithelial‑mesenchymal transition (EMT), migration and invasion were evaluated by western blotting and transwell assay. The association between miR‑212‑3p and ZEB2 was investigating by the luciferase activity. The results showed that treatment of HCC cells with PTX inhibited cell viability and miR‑212‑3p level. Moreover, miR‑212‑3p was reduced and its overexpression resulted in decreased cell viability, half maximal inhibitory concentration (IC₅₀) of PTX and levels of P‑glycoprotein and glutathione S‑transferase π, but increased cell apoptosis, in Huh7/PTX cells. However, miR‑212‑3p knockdown induced opposite effects in Huh7 cells. Furthermore, EMT, migration and invasion were induced in Huh7/PTX cells and the addition of miR‑212‑3p inhibited EMT, migration and invasion. Meanwhile, miR‑212‑3p abrogation caused the opposite effects in Huh7 cells. Additionally, ZEB2 was directly targeted by miR‑212‑3p and its restoration or silencing abated the effect of miR‑221‑3p overexpression or knockdown in Huh7/PTX or Huh7 cells, respectively. The data from the present study suggest that miR‑212‑3p attenuates PTX resistance, by regulating EMT, migration and invasion via targeting ZEB2 in HCC cells, indicating a novel target for HCC chemotherapy.

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