Pseudo - Gene PTENP1 Affects The Progression Of Gastric Cancer By Regulating The Expression Of PTEN Protein

Background:Long non-coding RNAs are a class of RNAs which are more than 200 nt in length with limited or no protein-coding capacity. Recently, multiple lines of evidence have revealed that lnc RNAs can play crucial role in many biological processes such as cell proliferation, cell cycle differentiation, and apoptosis, mainly by regulation of gene expression at various levels, including epigenetic regulation, transcriptional and post-transcriptional regulation. Pseudogenes-expressed RNAs also belong to the category of lnc RNAs. Pseudogenes are previously considered biologically inconsequential, but recently some of them have been discovered to play pivotal role in carcinogenesis. PTENP1 has been demonstrated to function as a tumor suppressor in several cancer cells. However, its expression and biological roles in gastric cancer(GC) have not yet been investigated.Objective:This study aimed to explore the expression of PTENP1 in GC tissues and cell lines, and investigate the correlation between PTENP1 expression levels in GC tissues and clinicopathological factors in GC patients, as well as the biological role and underlying mechanism of PTENP1 in GC cells.Methods:Expressions of PTENP1 were analyzed in 68 GC tissues and 4 GC cell lines by q RT-PCR. Over-expression approaches were used to investigate the biological functions of PTENP1 3’UTR in GC cells. Treatment of 5-aza-d C was used to investigate DNA methylation on PTENP1 expression. The effect of PTENP1 on proliferation was evaluated by CCK-8 and colony formation assays, and cell apoptosis was evaluated by Hoechst staining as well as Flow-cytometric analysis.Moreover, the role of PTENP1 3’UTR on migration and invasion of GC cells was analyzed by transwell and wound healing assay. Protein level of PTEN was determined by western blot analysis.Results:In this study, we demonstrated that PTENP1 was frequently decreased in GC tissues and cell lines, which might be partly associated with DNA hypermethylation, and lower PTENP1 expression was associated with larger tumor size, more advanced stage, deeper invasion depth and lymphatic metastasis. In addition, our data suggested that PTENP1 could regulate GC cell proliferation, apoptosis, migration and invasion in vitro. Furthermore, we demonstrated that PTENP1 could modulate the PTEN protein expression.Conclusions:Taken together, these results suggest that PTENP1 functions as a novel tumor suppressor in GC and its suppressive ability may be involved in the modulation of PTEN.