期刊
ANTI-CANCER DRUGS
卷 33, 期 9, 页码 840-849出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CAD.0000000000001329
关键词
hepatocellular carcinoma; KDM5B; PTEN; P13K; Akt pathway; stem cell properties; sorafenib-sensitivity
The study found that KDM5B influences cancer stem cell properties and sorafenib-resistance in hepatocellular carcinoma cells by modulating the PTEN/PI3K/Akt pathway, suggesting that KDM5B could be a potential target for the treatment of HCC.
Lysine-specific demethylase 5B (KDM5B) exerts its tumor-promoting functions in numerous malignancies, although the possible mechanisms by which KDM5B promotes cancer aggressiveness in hepatocellular carcinoma (HCC) have been preliminarily explored, the role of this gene in regulating sorafenib-resistance in HCC has not been studied. Thus, the present study was designed to resolve this problem, and our data suggested that KDM5B was significantly upregulated in the HCC tissues collected from patients with sorafenib treatment history. Consistently, continuous low-dose sorafenib administration increased KDM5B expression levels in the sorafenib-resistant HCC cells compared to their sorafenib-sensitive counterparts. Next, by performing the functional experiments, we found that KDM5B positively regulated sorafenib-resistance and cancer stem cell (CSC) properties in HCC cells in vitro and in vivo. Furthermore, upregulation of KDM5B-degraded phosphatase and tensin homolog (PTEN), results in the activation of the downstream oncogenic PI3K/Akt pathway. Subsequently, the rescuing experiments verified that the promoting effects of KDM5B overexpression on chemoresistance and cancer stemness in HCC cells were all abrogated by PI3K (p110) knockdown and PTEN overexpression. Collectively, those data hinted that KDM5B influenced CSC properties and sorafenib-resistance in HCC cells through modulating the PTEN/PI3K/Akt pathway, and KDM5B could be used as a potential target for the treatment of HCC in clinic.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据