Lin Xiu-Juan, He Chang-Li, Sun Ting, Duan Xue-Jing, Sun Yi, Xiong Shi-Jiang
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.
Int J Mol Med. 2017 Jul;40(1):83-89. doi: 10.3892/ijmm.2017.2992. Epub 2017 May 16.
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.
口腔鳞状细胞癌（OSCC）是目前全球范围内一种高度流行的疾病。顺铂（CDDP）被广泛用于OSCC的化疗。然而，导致顺铂耐药的分子机制尚未完全阐明。在本研究中，我们发现p21（RAC1）激活激酶1（PAK1）的过表达诱导上皮-间质转化（EMT），并显著促进口腔鳞状细胞癌SCC25细胞的侵袭和迁移。新出现的证据表明，癌症对治疗的耐药性与EMT的诱导之间存在密切联系。我们发现PAK1的过表达诱导SCC25细胞产生顺铂耐药性。ERCC1和YAP可促进人OSCC的顺铂耐药性。我们发现SCC25细胞中PAK1可上调ERCC1和YAP蛋白的表达。我们发现miR-485-5p抑制SCC25细胞中PAK1蛋白的表达。与PAK1相反，我们证明miR-485-5p的过表达可逆转EMT，并显著抑制侵袭和迁移。此外，其过表达使SCC25-CR细胞（顺铂耐药细胞）对顺铂敏感。因此，我们得出结论，miR-485-5p通过靶向口腔舌鳞状细胞癌中的PAK1逆转EMT并促进顺铂诱导的细胞死亡。本研究表明，PAK1在OSCC的进展中起重要作用，它是OSCC的一个潜在治疗靶点。
