miR‑375/Yes‑associated protein axis regulates IL‑6 and TGF‑β expression, which is involved in the cisplatin‑induced resistance of liver cancer cells

Yu,Kanru; Li,Hao; Jiang,Zhongyi; Hsu,Han-Jen; Hsu,Hsing-Chun; Zhang,Yumei; Wang,Kunwei

doi:10.3892/or.2021.8112

miR‑375/Yes‑associated protein axis regulates IL‑6 and TGF‑β expression, which is involved in the cisplatin‑induced resistance of liver cancer cells

Authors:
- Kanru Yu
- Hao Li
- Zhongyi Jiang
- Han-Jen Hsu
- Hsing-Chun Hsu
- Yumei Zhang
- Kunwei Wang
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Affiliations: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China, Department of Urology, Shanghai ZhongShan Hospital, Fudan University School of Medicine, Shanghai 200123, P.R. China, Department of Surgery, Shanghai Ruibo Clinic, Shanghai 200023, P.R. China, Department of VIP Clinical, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, P.R. China, Department of Endocrinology, Shanghai Tianyou Hospital, School of Medicine, Tongji University, Shanghai 200331, P.R. China
Published online on: June 14, 2021 https://doi.org/10.3892/or.2021.8112
Article Number: 162

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Abstract

Chemotherapy resistance is one of the major challenges in the treatment of liver cancer (LC). The present study aimed to investigate the potential roles of Yes‑associated protein (YAP), the core component of the Hippo signaling pathway, in chemoresistance of LC. YAP expression and its function in chemoresistance of LC cells were investigated. It was revealed that the expression levels and nuclear localization of YAP were increased in cisplatin (CDDP)‑resistant LC (LC/CDDP) cells. The targeted inhibition of YAP using small interfering RNA or an inhibitor restored the CDDP sensitivity of LC cells. YAP overexpression was discovered to be essential for the increase of IL‑6 and TGF‑β expression levels in LC/CDDP cells. Furthermore, it was identified that increased mRNA stability was the primary reason for the upregulation of YAP expression in LC/CDDP cells, which was due to the downregulation of microRNA (miR)‑375 expression in LC/CDDP cells. In conclusion, the findings of the present study suggested that the miR‑375/YAP axis may regulate the expression levels of IL‑6 and TGF‑β, which may subsequently be involved in the CDDP resistance of LC cells. The current results indicated that the targeted inhibition of this axis and signaling pathway may be helpful in overcoming CDDP resistance.

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