1. NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410078, People's Republic of China.
2. Hunan Cancer Hospital, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410078, People's Republic of China.
3. Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, 410078, People's Republic of China.
# These authors equally contributed to this work.
Background/Aim: Some long non-coding RNAs (lncRNAs) have been found to significantly participate in the progression of TGCTs. In comparison to the normal testis, the TGCT tissues showed significantly decreased CSNK1G2-AS1 expression, however, its effect on TGCTs and its mechanism are still unclear. The aim of this study is to investigate the effect of CSNK1G2-AS1 on TGCTs and explore the mechanism underlying its effect on TGCTs.
Materials and Methods: In this study, to evaluate the expression of CSNK1G2-AS1 in tissue samples from TGCTs, the UCSC and GEPIA databases were applied and qRT-PCR was conducted. The Kaplan-Meier Plotter was applied to analyze the correlation between CSNK1G2-AS1 methylation levels and the prognosis of TGCTs patients. The assays of MTS, clone formation, transwell, and flow cytometry were performed to investigate the effect of CSNK1G2-AS1 overexpression on the proliferation, metastasis, and apoptosis of TGCT cells, respectively. Finally, western blotting was conducted to determine the expressions of the proteins associated with EMT and AKT.
Results: Our study first found that, compared to the normal testis, TGCTs tissue showed significantly decreased CSNK1G2-AS1 expression, and hypomethylation of CSNK1G2-AS1 was significantly correlated with a better prognosis with TGCTs patients. In vitro, we found that overexpression of CSNK1G2-AS1 dramatically promoted the clone formation, invasion, and migration of TGCT cells, but inhibited apoptosis. And CSNK1G2-AS1 overexpression significantly decreased the expression of EMT-associated proteins ZO-1 but increased the expression and phosphorylation of AKT.
Conclusions: CSNK1G2-AS1 may play an essential role in the pathogenesis and metastasis of TGCTs through the EMT- and AKT-mediated signal pathways.
Keywords: Testicular germ cell tumors (TGCTs), long noncoding RNA (lncRNA), metastasis, EMT, AKT