MiR-204 enhances mitochondrial apoptosis in doxorubicin-treated prostate cancer cells by targeting SIRT1/p53 pathway
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Yan Shu1, Ligang Ren1, Bo Xie1, Zhen Liang2 and Jing Chen1
1Department of Urology, Tongde Hospital of Zhejiang Province, Hangzhou 310012, China
2Department of Urology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
Jing Chen, email: [email protected]
Keywords: prostate cancer, doxorubicin, miR-204, SIRT1, p53
Received: August 09, 2017 Accepted: September 24, 2017 Published: October 23, 2017
Chemotherapy is important for adjuvant treatment of prostate cancer. However, some cancer cells exhibited low sensitivity to chemotherapeutic agents. We are supposed to sensitize these prostate cancer cells to chemotherapeutic agents such as doxorubicin. Previous reports have suggested that microRNAs (miRNAs) regulate chemosensitivity in various cancers. In the present study, we observed that expression level of miR-204 was decreased in prostate cancer cell lines and patients’ tumors. Furthermore, we found that restore of miR-204 dramatically enhanced the cytotoxicity of doxorubicin (DOX) against prostate cancer cell lines C4-2 and LNCaP carrying wild type (WT) p53. Mechanically, miR-204 in prostate cancer cells targets SIRT1 which is a histone deacetylase, and thus decreasing deacetylation of p53. As the results, acetylated p53 induced by DOX upregulates the expression of Noxa and Puma followed by induction of mitochondrial apoptosis. These data demonstrate that restore of miR-204 in prostate cancer cells enhances the mitochondrial apoptosis induced by doxorubicin by targeting the SIRT1/p53 pathway.
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