摘要
The abnormal expression of long noncoding RNAs(lncRNAs)is frequently observed in gastric cancer(GC)and considered an important driving force in GC progression.However,little is known regarding the involvement of TMEM147-AS1 in GC.Therefore,we examined TMEM147-AS1 expression in GC and determined its prognostic value.In addition,TMEM147-AS1 expression was depleted to identify the functional changes in response to TMEM147-AS1 deficiency.Using the cancer genome atlas dataset and our own cohort,we identified a strong expression of TMEM147-AS1 in GC.Increased TMEM147-AS1 levels in GC showed a significant association with poor prognosis.TMEM147-AS1 interference resulted in the inhibition of GC cell proliferation,colony-forming,migration,and invasion in vitro.Additionally,depletion of TMEM147-AS1 restricted the growth of GC cells in vivo.Mechanistically,TMEM147-AS1 functioned as a microRNA-326(miR-326)sponge.Furthermore,SMAD family member 5(SMAD5)was experimentally validated as the functional effector of miR-326.TMEM147-AS1 was demonstrated to sequester miR-326 away from SMAD5;consequently,knocking down TMEM147-AS1 downregulated SMAD5 levels in GC cells.The functional suppression of miR-326 or reintroduction of SMAD5 effectively reversed the attenuated behavior of GC cells caused by TMEM147-AS1 downregulation.In summary,TMEM147-AS1 exhibits tumorigenic activities in GC,which is likely the result of an altered miR-326/SMAD5 axis.Therefore,targeting TMEM147-AS1/miR-326/SMAD5 may represent a target for the treatment of GC.
