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HIF1α promotes prostate cancer progression by increasing ATG5 expression

Animal Cells and Systems 2019년 23권 5호 p.326 ~ 334
Yu Kaiyuan, Xiang Luxia, Li Shaoxun, Wang Shuaibin, Chen Chaohao, Mu Haiqi,
소속 상세정보
 ( Yu Kaiyuan ) - Wenzhou Medical University Second Affiliated Hospital and Yuying Children’s Hospital
 ( Xiang Luxia ) - Wenzhou Medical University Second School of Medicine
 ( Li Shaoxun ) - Wenzhou Medical University Second School of Medicine
 ( Wang Shuaibin ) - Wenzhou Medical University Second Affiliated Hospital and Yuying Children’s Hospital
 ( Chen Chaohao ) - Wenzhou Medical University Second Affiliated Hospital and Yuying Children’s Hospital
 ( Mu Haiqi ) - Wenzhou Medical University Second Affiliated Hospital and Yuying Children’s Hospital

Abstract


Prostate cancer (PCa) is the most frequently diagnosed cancer among men. However, the major modifiable risk factors for PCa are poorly known and its specific mechanism of progression remains unclear. Here we reported that, in prostate cancer cells, the autophagy level was elevated under hypoxic condition, as well as the mRNA and protein level of ATG5, which is an important gene related to autophagy. Furthermore, we found HIF1α could directly bind to the promoter of ATG5 and promote the expression of ATG5 on transcriptional level by luciferase assay and ChIP assay. Intriguingly, overexpression of HIF1α by HIF1α-M could increase tumor size and the effect could be abolished by knockdown ATG5 by si-ATG5 in BALB/cA-nu/nu nude mice. Importantly, HIF1α could also promote the metastasis of PC-3 cells by upregulating the ATG5 and autophagy level and knockdown ATG5 and inhibition autophagy both could abolish the effect of overexpression of HIF1α on the migration of PC-3 cells. Taken together, our results, for the first time, proved that HIF1α could promote the proliferation and migration of PC-3 cells by direct upregulating ATG5 and autophagy level in PC-3 prostate cancer cells. Our findings not only provide new perspective for the relationship between hypoxia and autophagy, but also add new potential therapeutic regimens for the treatment of prostate cancers.

키워드

HIF1α; ATG5; autophagy; PC-3 cell

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