Reciprocal repression between TUSC7 and miR-23b in gastric cancer

Recently, long noncoding RNAs (lncRNAs) were demonstrated to play important regulatory roles in biological processes and cancer biology. However, the overall pathophysiological contribution of lncRNAs to gastric cancer (GC) remains largely unknown. In this study, differentially expressed lncRNAs in GC and paired adjacent normal tissue samples were identified by microarray and were validated using quantitative real-time polymerase chain reaction (qRT-PCR). One particular lncRNA, tumour suppressor candidate 7 (TUSC7), was analyzed in sequential large cohorts, and the Kaplan-Meier method with the log-rank test for comparisons was used to analyse the survival data. The results indicated that TUSC7 was downregulated in GC samples and was an independent prognostic indicator of disease-free survival (DFS) and disease-specific survival (DSS) in GC patients. Applying loss-of-function and gain-of-function approaches, we determined that TUSC7 suppressed tumour cell growth in vitro and in vivo. Furthermore, we showed that TUSC7 was a direct transcriptional target of p53 via interaction of p53 with the putative p53-response element in the upstream region of TUSC7. Finally, we demonstrated reciprocal repression between TUSC7 and miR-23b; in contrast to TUSC7, miR-23b promoted cell growth. The results indicated that TUSC7 is a p53-regulated tumour suppressor that acts in part by repressing miR-23b and that TUSC7 may be a key regulatory hub in GC. What's new? Long noncoding RNA expression could predict gastric cancer survival, new data suggest. It's been shown previously that these transcripts can function as tumor suppressors, and in this paper the authors investigate lncRNAs in gastric cancer. First, they identified lncRNAs that were expressed differently in cancer cells than healthy ones. By performing a cohort analysis they showed that patients with one particular lncRNA, called TUSC7, had a greater chance of survival. They then demonstrated that p53 regulates TUSC7 transcription, and that TUSC7 represses miR-23b, which spurs cell growth. Thus, TUSC7 may act as a tumor suppressor.