hsa-miR-485-5p reverses epithelial to mesenchymal transition and promotes cisplatin-induced cell death by targeting PAK1 in oral tongue squamous cell carcinoma

Lin,Xiu-Juan; He,Chang-Li; Sun,Ting; Duan,Xue-Jing; Sun,Yi; Xiong,Shi-Jiang

doi:10.3892/ijmm.2017.2992

hsa-miR-485-5p reverses epithelial to mesenchymal transition and promotes cisplatin-induced cell death by targeting PAK1 in oral tongue squamous cell carcinoma

Authors:
- Xiu-Juan Lin
- Chang-Li He
- Ting Sun
- Xue-Jing Duan
- Yi Sun
- Shi-Jiang Xiong
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Affiliations: Department of VIP Center and Shandong Provincial Key Laboratory of Oral Biomedicine, School and Hospital of Stomatology, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Stomatology, Qianfoshan Hospital Affiliated to Shandong University, Jinan, Shandong 250014, P.R. China, Department of Stomatology, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, P.R. China, Department of Stomatology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Department of Special Clinic, Weifang Stomatological Hospital, Weifang, Shandong 261021, P.R. China
Published online on: May 16, 2017 https://doi.org/10.3892/ijmm.2017.2992
Pages: 83-89
Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Oral squamous cell carcinoma (OSCC) is currently a highly prevalent disease worldwide. Cisplatin (CDDP) is widely used for the chemotherapy of OSCC. Yet, the molecular mechanisms responsible for cisplatin resistance have not been fully elucidated. In this study, we showed that overexpression of p21 (RAC1) activated kinase 1 (PAK1) induced epithelial to mesenchymal transition (EMT) and significantly promoted the invasion and migration of oral squamous cell carcinoma SCC25 cells. Emerging evidence indicates a strong link between resistance to therapy and the induction of EMT in cancer. We showed that overexpression of PAK1 induced cisplatin resistance in SCC25 cells. ERCC1 and YAP can promote cisplatin resistance in human OSCC. We showed that ERCC1 and YAP protein were upregulated by PAK1 in SCC25 cells. We found that miR‑485‑5p inhibited PAK1 protein expression in the SCC25 cells. Contrary to PAK1, we demonstrated that overexpression of miR‑485‑5p reversed EMT and significantly inhibited invasion and migration. Moreover, its overexpression sensitized SCC25-CR cells (cisplatin-resistant cells) to cisplatin. Thus, we conclude that miR‑485‑5p reverses EMT and promotes cisplatin-induced cell death by targeting PAK1 in oral tongue squamous cell carcinoma. This study suggests that PAK1 plays an essential role in the progression of OSCC and it is a potential therapeutic target for OSCC.

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