Long noncoding RNA TMEM147-AS1 serves as a microRNA-326 sponge to aggravate the malignancy of gastric cancer by upregulating SMAD5

Abstract

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.