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Upregulation of GRIM‐19 augments the sensitivity of prostate cancer cells to docetaxel by targeting Rad23b
Author(s) -
Lin Haili,
Shen Zaixiong,
Liu Hongjie,
Yang Minggen,
Lin Jiangui,
Luo Liutao,
Liu Linyong,
Chen Hong
Publication year - 2020
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13179
Subject(s) - docetaxel , apoptosis , downregulation and upregulation , cancer research , prostate cancer , dna damage , cell culture , cancer cell , flow cytometry , western blot , biology , microbiology and biotechnology , cancer , chemistry , gene , dna , genetics
The gene associated with retinoid‐interferon mortality (GRIM‐19) has been reported to be correlated with drug resistance, whereas its functional role in prostate cancer (PC) is not fully understood. This study aims to clarify the potential role and molecular mechanisms of GRIM‐19 on the response of PC cells to chemical drug docetaxel. mRNA and protein level of GRIM‐19 expression in cells and tissues of PC were measured by quantitative real‐time PCR and western blot, respectively. Knock‐down of GRIM‐19 in PC cells was performed using siRNA. Cell apoptosis was determined by flow cytometric analysis. DNA damage in PC cells was detected by γ‐H2AX staining. GRIM‐19 was downregulated in PC tissues and cell lines. Knock‐down of GRIM‐19 increased the resistance of PC cells to docetaxel, and overexpression of GRIM‐19 promoted docetaxel‐induced apoptotic death in PC cells. Mechanistically, GRIM‐19 downregulated the expression of the survival gene Rad23b, which promoted DNA damage repair. Overexpression of Rad23b reversed GRIM‐19‐mediated response to docetaxel in PC cells. GRIM‐19 promoted the sensitivity of PC cells to docetaxel by downregulating Rad23b, which may serve as a promising target to develop a better strategy of chemotherapy for PC.