Long noncoding RNAs (lncRNAs) are emerging as new players in gene regulation and are associated with the development of cancers. To investigate the important role and mechanism of lncRNAs in the progression of gastric cancer, we screened lncRNAs in gastric cancer tissues and corresponding adjacent tissues, and assessed the effects on gastric cancer. Here, we report that BC032469, a novel lncRNA, expressed highly in gastric cancer tissues, and the upregulation was clinically associated with larger tumor size, poor differentiation and shorter survival of gastric cancer patients. Downregulation of BC032469 resulted in a significant inhibition of proliferation in vitro and in vivo. Mechanistically, BC032469 could directly bind to miR-1207-5p and effectively functioned as a sponge for miR-1207-5p to modulate the derepression of hTERT. Thus, BC032469 may function as a ceRNA to impair miR-1207-5p-dependent hTERT downregulation, suggesting that it may be clinically valuable as a poor prognostic biomarker of gastric cancer.

hTERT is the catalytic subunit of the telomerase complex. Elevated expression of hTERT is associated with the expansion and metastasis of gastric tumor. In this study, we aimed to identify novel tumor suppressor miRNAs that restrain hTERT expression. We began our screen for hTERT-targeting miRNAs with a miRNA microarray. miRNA candidates were further filtered by bioinformatic analysis, general expression pattern in different cell lines, gain-of-function effects on hTERT protein and the potential of these effects to suppress hTERT 3′ untranslated region (3′UTR) luciferase activity. The clinical relevance of two miRNAs (miR-1207-5p and miR-1266) was evaluated by real-time RT-PCR. The effects of these miRNAs on cell growth, cell cycle and invasion of gastric cancer cells were measured with CCK-8, flow cytometry and transwell assays. Finally, the ability of these miRNAs to suppress the transplanted tumors was also investigated. Fourteen miRNAs were identified using a combination of bioinformatics and miRNA microarray analysis. Of these fourteen miRNAs, nine were expressed at significantly lower levels in hTERT-positive cell lines compared with hTERT-negative cell lines and five could downregulate hTERT protein expression. Only miR-1207-5p and miR-1266 interacted with the 3′ UTR of hTERT and the expression levels of these two miRNAs were significantly decreased in gastric cancer tissues. These two miRNAs also inhibited gastric tumor growth in vitro and in vivo. Altogether, miR-1207-5p and miR-1266 were determined to be hTERT suppressors in gastric cancer, and the delivery of these two miRNAs represents a novel therapeutic strategy for gastric cancer treatment.

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