miR-199a-3p enhances cisplatin sensitivity of ovarian cancer cells by targeting ITGB8
| Autor: | Peilian Zhang, Fengqin Wu, Li Qin, Ting Wang, Yajie Cui, Defu Tian, Xiying Huang, Tianjie Lu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
inorganic chemicals Cancer Research miR-199a-3p endocrine system diseases Cell CDDP sensitivity 03 medical and health sciences 0302 clinical medicine ITGB8 Cell Movement Cell Line Tumor medicine Humans neoplasms Aged Cell Proliferation Cisplatin Ovarian Neoplasms Oncogene Chemistry Cell growth Integrin beta1 Cell Cycle Cancer General Medicine Articles Cell cycle Middle Aged medicine.disease female genital diseases and pregnancy complications Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology medicine.anatomical_structure ovarian cancer Oncology Apoptosis Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research Female Ovarian cancer medicine.drug |
| Zdroj: | Oncology Reports |
| ISSN: | 1791-2431 1021-335X |
| Popis: | Drug resistance remains a large obstacle for the treatment of ovarian cancer. miRNAs have been reported to be involved in cisplatin (CDDP) resistance in ovarian cancer. The aim of the present study was to investigate the function and mechanism of miR-199a-3p in the CDDP resistance in ovarian cancer. We found that miR-199a-3p was significantly downregulated in chemoresistant ovarian cancer tissues, as well as CDDP-resistant SKOV3/CDDP cells, compared to chemosensitive carcinomas and SKOV3 cells. Restoration of miR-199a-3p in SKOV3/CDDP cells reduced cell proliferation, G1 phase cell cycle arrest, cell invasion, and increased cell apoptosis, resulting in enhanced CDDP sensitivity, while miR-199a-3p inhibition resulted in the opposite effects. Luciferase reporter assay showed that integrin β8 (ITGB8), one of the integrins that is involved in the regulation of cell cycle and motility, was a direct target of miR-199a-3p. Overexpression of miR-199a-3p downregulated ITGB8 expression via binding to its 3′-UTR. In addition, overexpression of ITGB8 restored CDDP resistance inhibited by miR-199a-3p. Moreover, orthotopic ovarian cancer mouse model showed that miR-199a-3p enhanced CDDP sensitivity of ovarian cancer in vivo. Therefore, our results indicate that miR-199a-3p enhances CDDP sensitivity of ovarian cancer cells through downregulating ITGB8 expression, and miR-199a-3p may serve as a therapeutic target for the treatment of ovarian cancer patients with CDDP-resistance. |
| Databáze: | OpenAIRE |
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