期刊
ONCOTARGET
卷 8, 期 45, 页码 79023-79033出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.20784
关键词
laryngeal cancer; Hep-2/R; miR-26b; ATF2; cisplatin
资金
- National Science Foundation of China [81402234, 81572647, 81372902]
- Heilongjiang Educational Committee [12541292, 12531343]
Cisplatin is a common used chemotherapeutic drug for the treatment of laryngeal cancer. However, drug-resistance is a major obstacle in platinum-based chemotherapy for laryngeal cancer. Recent studies have demonstrated that dysregulation of microRNAs (miRNAs) is responsible for chemoresistance in multiple cancers including laryngeal cancer, but the potential mechanisms are required to be explored. In the present study, we constantly exposed the laryngeal cancer cell line Hep-2with cisplatin to establish a cisplatin-resistant laryngeal cancer cell model (Hep-2/R). We found that Hep-2/R cells exhibited obvious resistance to cisplatin compared to the Hep-2 cells. However, overexpression of miR-26b significantly decreased the half maximal inhibitory concentration (IC50) of cisplatin to Hep-2/R. Mechanically, miR-26b in Hep-2/R decreased the expression of ATF2, and thus inhibiting the phosphorylation of ATF2 and formation of cellular ATF2-c-Jun complex induced by cisplatin. As the results, Hep-2/R cells failed to overexpress the Bcl-xl which is a key anti- apoptotic protein under the cisplatin treatment. Therefore, overexpression of miR-26b was found to be able to promote mitochondrial apoptosis induced by cisplatin.
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