LncRNA CR749391 acts as a tumor suppressor to upregulate KLF6 expression via interacting with miR-181a in gastric cancer

摘要

Long non-coding RNAs (lncRNAs) are novel regulators for post-transcriptional gene expression, and altered lncRNAs function and expression are associated with tumorigenesis and cancer progression, although the biological functions of most lncRNAs in various cancer types and their underlying regulatory interactions have remained largely elusive. Our previous study identified microRNA (miR)-181a as a regulator of Kruppel-like factor 6 (KLF6). In the present study, a bioinformatical analysis was performed to identify the novel lncRNA as a potential regulator of miR-181a that contains four putative binding sites. Subsequent experiments in gastric cancer (GC) cells demonstrated that interacted with miR-181a to regulate KLF6 expression. First, a direct binding interaction was confirmed using luciferase reporter and RNA immunoprecipitation and pull-down assays. In addition, was observed to be downregulated in GC compared with that of normal gastric cell lines. A functional study also revealed that depletion in normal gastric epithelial cells promoted cell viability, migration and invasion, and conferred resistance to apoptosis, whereas ectopic overexpression had the opposite effect in GC cells and inhibited tumor growth. In addition, was observed to be downregulated in GC compared with that of normal gastric tissues, which was associated with KLF6 but inversely associated with miR-181a levels. Overall, the /miR-181a regulatory interaction and association between and KLF6 may enhance the current understanding of GC pathogenesis, although association with GC prognosis needs further study. The current study could provide a novel approach for lncRNA-mediated targeted GC therapy.