TY - JOUR T1 - Heat shock protein 90 promotes RNA helicase DDX5 accumulation and exacerbates hepatocellular carcinoma by inhibiting autophagy JF - Cancer Biology and Medicine JO - Cancer Biol Med SP - 693 LP - 704 DO - 10.20892/j.issn.2095-3941.2020.0262 VL - 18 IS - 3 AU - Ting Zhang AU - Xinrui Yang AU - Wanping Xu AU - Jing Wang AU - Dawei Wu AU - Zhixian Hong AU - Shengxian Yuan AU - Zhen Zeng AU - Xiaodong Jia AU - Shanshan Lu AU - Rifaat Safadi AU - Sen Han AU - Zhihong Yang AU - Leonard M. Neckers AU - Suthat Liangpunsakul AU - Weiping Zhou AU - Yinying Lu Y1 - 2021/08/01 UR - http://www.cancerbiomed.org/content/18/3/693.abstract N2 - Objective: Hepatocellular carcinoma (HCC), the main type of liver cancer, has a high morbidity and mortality, and a poor prognosis. RNA helicase DDX5, which acts as a transcriptional co-regulator, is overexpressed in most malignant tumors and promotes cancer cell growth. Heat shock protein 90 (HSP90) is an important molecular chaperone in the conformational maturation and stabilization of numerous proteins involved in cell growth or survival.Methods: DDX5 mRNA and protein expression in surgically resected HCC tissues from 24 Asian patients were detected by quantitative real-time PCR and Western blot, respectively. The interaction of DDX5-HSP90 was determined by molecular docking, immunoprecipitation, and laser scanning confocal microscopy. The autophagy signal was detected by Western blot. The cell functions and signaling pathways of DDX5 were determined in 2 HCC cell lines. Two different murine HCC xenograft models were used to determine the function of DDX5 and the therapeutic effect of an HSP90 inhibitor.Results: HSP90 interacted directly with DDX5 and inhibited DDX5 protein degradation in the AMPK/ULK1-regulated autophagy pathway. The subsequent accumulation of DDX5 protein induced the malignant phenotype of HCC by activating the β-catenin signaling pathway. The silencing of DDX5 or treatment with HSP90 inhibitor both blocked in vivo tumor growth in a murine HCC xenograft model. High levels of HSP90 and DDX5 protein were associated with poor prognoses.Conclusions: HSP90 interacted with DDX5 protein and subsequently protected DDX5 protein from AMPK/ULK1-regulated autophagic degradation. DDX5 and HSP90 are therefore potential therapeutic targets for HCC. ER -