hsa-miR-485-5p reverses epithelial to mesenchymal transition and promotes cisplatin-induced cell death by targeting PAK1 in oral tongue squamous cell carcinoma
| Autor: | Xiu-Juan Lin, Chang-Li He, Ting Sun, Xue-Jing Duan, Yi Sun, Shi-Jiang Xiong |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition Cell RAC1 Biology 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Genetics medicine Carcinoma Humans Neoplasm Invasiveness Epithelial–mesenchymal transition RNA Neoplasm Cisplatin Oncogene Cell Death miR-485-5p General Medicine Articles Cell cycle medicine.disease Neoplasm Proteins Tongue Neoplasms oral squamous cell carcinoma stomatognathic diseases MicroRNAs 030104 developmental biology medicine.anatomical_structure p21-Activated Kinases Apoptosis 030220 oncology & carcinogenesis p21 (RAC1) activated kinase 1 Cancer research Carcinoma Squamous Cell cisplatin resistance medicine.drug |
| Zdroj: | International Journal of Molecular Medicine |
| ISSN: | 1791-244X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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