中国药理学通报2024，Vol.40Issue(4)：679-687,9.DOI:10.12360/CPB202312001
lncRNA ENST00000452996.1通过ERK/GSK-3β/β-catenin信号通路调控肝癌细胞增殖、迁移及侵袭
lncRNA ENST00000452996.1 promotes HCC proliferation,migration and invasion by regulating ERK/GSK-3β/β-catenin signaling pathway
摘要
Abstract
Aim To investigate a novel lncRNA,ENST00000452996.1,and its biological function and underlying mechanism in hepatocellular carcinoma(HCC)progression.Methods The expression pat-tern and clinical pathobiological relevance of ENST00000452996.1 in HCC were analyzed using the Cancer Genome Atlas(TCGA)dataset.The shRNA lentiviral vector targeting ENST00000452996.1 gene was constructed and infected into Huh-7 cells(shENST00000452996.1 group).Cell proliferation,apoptosis,migration,and invasion were measured u-sing CCK-8 assay,colony formation assay,Annexin V-FITC/PI staining,wound healing assay and Transwell assay,respectively.The expression of the molecules related to the ERK/GSK-3 β/β-catenin signaling path-way in the shENST00000452996.1 group,EGF group and TDZD-8 group were evaluated by Western blot.Results ENST00000452996.1 was upregulated in HCC tissues and was positively associated with an ad-vanced Edmondson-Steiner grade.Kaplan-Meier analy-sis revealed that high expression of ENST00000452996.1 was related to poorer overall survival of HCC patients in TCGA database.Compared with the control group,shENST00000452996.1 suppressed the prolif-eration,migration and invasion,and promoted apopto-sis in Huh-7 cells.Western blot assay showed that shENST00000452996.1 downregulated the expression of p-ERK1/2,p-GSK-3βSer9,β-catenin and the nucle-ar levels of β-catenin,while upregulated the expres-sion of GSK-3β and p-β-catenin.Compared with the shENST00000452996.1 group,EGF significantly in-creased the levels of p-ERK1/2,EGF and TDZD-8 both increased the levels of p-GSK-3β,total β-catenin and nuclear levels of β-catenin,whereas reduced the levels of GSK-3β and p-β-catenin.Conclusions Knockdown of ENST00000452996.1 can suppress the phosphorylation of ERK1/2,which in turn prevents phosphorylation of GSK3 β at Ser9,leading to phospho-rylation of β-catenin and inhibition of β-catenin nucle-ar translocation.lncRNA ENST0000045299 6.1 pro-motes HCC cell proliferation,migration and invasion by regulating ERK/GSK-3β/β-catenin signaling path-way,which plays a key role in the progression of HCC.关键词
长链非编码RNA/ENST00000452996.1/肝细胞癌/增殖/侵袭/ERK/GSK-3β/β-cateninKey words
long non-coding RNA/ENST00000452996.1/hepatocellular carcinoma/pro-liferation/invasion/ERK/GSK-3β/β-catenin分类
医药卫生引用本文复制引用
谢群,林丽彬,郑伟男,徐丽,林扬元..lncRNA ENST00000452996.1通过ERK/GSK-3β/β-catenin信号通路调控肝癌细胞增殖、迁移及侵袭[J].中国药理学通报,2024,40(4):679-687,9.基金项目
福建省自然科学基金资助项目(No 2020J01919) （No 2020J01919）
