Zhaoliang Chen, Hong Liu, Huili Yang, Yukai Gao, Gongwen Zhang, Jiaojiao Hu

Accumulating evidence indicates that the long noncoding RNA, TINCR, plays a critical role in cancer progression and metastasis. However, the overall biological role and mechanisms of TINCR that were involved in human gastric cancer (GC) progression remain largely unknown. TINCR expression was measured in 56 paired tumor and adjacent nontumor tissue samples by real-time polymerase chain reaction (PCR). Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, luciferase assays. The effects of TINCR and miR-375 on GC cell apoptosis and proliferation were studied by RNA interference approaches in vitro and in vivo. The correlation of TINCR and PDK1 was identified by real-time PCR and Western blot analysis. Our results showed that miR-375 level decreased and TINCR level increased in tumor tissues. In addition, TINCR was a target of miR-375 and inhibited its expression in GC cells. Furthermore, the low expression of TINCR increased cell apoptosis and inhibited the proliferation of GC cells, while the downregulation of miR-375 reversed the function. In particular, TINCR could negatively regulate the miR-375 expression and increased the PDK1 expression in GC cells. Finally, tumor growth suppression was retarded with miR-375 downregulated in TINCR knockdown of GC cell xenografts. The long noncoding RNA TINCR functions as a competing endogenous RNA to regulate PDK1 expression by sponging miR-375 in GC. The ceRNA regulatory network of TINCR/miR-375/PDK1 allows us to better understand the pathogenesis of GC and facilitate the development of long noncoding RNA (lncRNA)-directed diagnostics in GC.