Long Non-Coding RNA TMPO-AS1 Promotes Malignant Behaviors of Hepatocellular Carcinoma Cells via YWHAG/ERK Pathway

Abstract

Increasing attention has been paid to long noncoding RNAs (lncRNAs) as they have been implicated in the tumorigenesis of many malignancies, such as hepatocellular carcinoma (HCC). The current research explored the pro-tumorigenic biological function of the lncRNA, TMPO-AS1, in HCC, and uncovered the underlying mechanism. The correlations between TMPO-AS1 expression and clinical outcome in HCC were analyzed based on GEO and KM plotter databases. The differential expression of TMPO-AS1 between normal liver and HCC tissues/cells was analyzed by real-time quantitative PCR. HepG2 and Huh7 cell lines were exploited in this study. The protein expression levels were analyzed by Western blot. Cell viability was determined by CCK-8 and colony formation experiments; while cell migration and invasion capacities were observed by wound healing and Transwell, respectively. RNA pulldown and RIP assay were adopted to determine the interaction between TMPO-AS1 and YWHAG. The TMPO-AS1 expression in HCC tissues was significantly higher than that in the normal tissues, and positively correlated with the tumor grade and poor prognosis in HCC patients. The ERK signaling pathway could be activated by overexpressing TMPO-AS1 but repressed by silencing TMPO-AS1 in HCC cells. Mechanically, TMPO-AS1 directly interacted with YWHAG and up-regulated its protein expression by inhibiting its ubiquitination. The effects causing by TMPO-AS1 overexpression and silence on the cell proliferation, migration, invasion, and EMT process of HCC cells could be blocked by YWHAG silence and overexpression, respectively. TMPO-AS1 may facilitate malignant behaviors of HCC cells by YWHAG/ERK pathway.