摘要
目的 探讨ROCK2是否通过调控MKP1表达影响肝癌细胞侵袭转移。方法 采用qRT-PCR及western blot方法以及CCK8和EDU实验,证实ROCK2是通过调控MKP1表达影响肝癌细胞侵袭转移。结果 MKP1在肝细胞癌(HCC)中的表达显著下调,并且MKP1是预后不良的独立预测因子。在体外和体内研究中,MKP1显著抑制HCC细胞的侵袭和转移。MKP1低表达与ROCK2表达有关,ROCK2在HCC中起着重要作用。数据表明MKP1在ROCK2介导的转移和侵袭中至关重要。ROCK2对MKP1的蛋白和转录水平调控不一致;ROCK2激活ERK1/2-ATF2信号传导,其导致MKP1的mRNA表达增加。ROCK2促进泛素通过激活ERK1/2介导MKP1的降解,从而促进HCC的转移。结论 ROCK2在HCC进展中干扰MKP1的蛋白和mRNA表达。MKP1可作为一种预测肿瘤侵袭转移的潜在生物标志物。
Objective To explore whether ROCK2 affects invasion and metastasis of liver cancer cells by regulating MKP1 expression.Methods Using qRT PCR and Western blot methods,as well as CCK8 and EDU experiments,it was confirmed that ROCK2 affects the invasion and metastasis of liver cancer cells by regulating the expression of MKP1.Results The expression of MKP1 was significantly downregulated in hepatocellular carcinoma(HCC),and MKP1 was an independent predictor of poor prognosis.In vitro and in vivo studies,MKP1 significantly inhibited the invasion and metastasis of HCC cells.The low expression of MKP1 was related to the expression of ROCK2,which plays an important role in HCC.MKP1 was crucial for ROCK2 mediated metastasis and invasion.The protein and transcriptional level regulation of MKP1 by ROCK2 was inconsistent;ROCK2 activated ERK1/2-ATF2 signaling,which lead to an increase in mRNA expression of MKP1.Meanwhile,ROCK2 promoted ubiquitin mediated degradation of MKP1 by activating ERK1/2,thereby promoted the transfer of HCC.Conclusion ROCK2 interferes with the protein and mRNA expression of MKP1 in HCC progression.MKP1 can serve as a potential biomarker for predicting tumor invasion and metastasis.
作者
周玮
芦珊
杜云艳
陈磊峰
ZHOU Wei;LU Shan;DU Yunyan(Jiangxi Cancer Hospital,Nanchang,330029)
出处
《实用癌症杂志》
2023年第11期1741-1749,共9页
The Practical Journal of Cancer
基金
国家自然科学基金(编号:82060449)
江西省自然科学基金(编号:20202BABL206084)
江西省肿瘤医院杰出青年(编号:2021DYS06)
江西省卫健委(编号:202310056)
江西省卫健委(编号:202310055)
江西省教育厅(编号:GJJ2203533)。
