Long non-coding RNA TTTY15 silencing inhibits gastric cancer progression by sponging microRNA-98-5p to down-regulate cyclin D2 expression

Abstract

ABSTRACT Gastric cancer is the most common malignant tumor in the digestive system. However, the detection rate of early gastric cancer is low, resulting in delayed prognosis and poor outcomes. The identification of effective therapeutic targets for gastric cancer is, therefore, of profound significance. Recently, various lncRNAs have been shown to be biomarkers for different cancers. This study investigated the role of long non-coding RNA (lncRNA) TTTY15 in gastric cancer. The expression level of TTTY15, miR-98-5p, and cyclin D2 (CCND2) were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot assay using tumor and non-tumor tissues collected from 30 patients with gastric cancer, gastric cancer cell lines (AGS, SNU-5, and NCI-N87), and the normal gastric epithelial cell line GES-1. The interaction between TTTY15 and miR-98-5p and between miR-98-5p and CCND2 were predicted by bioinformatics and then further verified by dual-luciferase and RNA pull-down analyses. Cell proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide (MTT) assay, and apoptosis was measured using flow cytometry and caspase-3 assay. The results indicate that TTTY15 and CCND2 expression increased and miR-98-5p expression decreased in gastric cancer tumor tissues and cell lines. TTTY15 knockdown inhibited gastric cancer cell proliferation but promoted apoptosis by sponging miR-98-5p, which acted as a tumor suppressor gene by reducing the expression of its target gene CCND2 in gastric cancer. In conclusion, lncRNA TTTY15 is a potential oncogene involved in gastric cancer and may be a novel therapeutic target for gastric cancer treatment.