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

Shi,Shengli; Li,Defeng; Li,Yingfei; Feng,Zhiqiang; Du,Yanlei; Nie,Yuqiang

doi:10.3892/etm.2019.8226

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

Authors:
- Shengli Shi
- Defeng Li
- Yingfei Li
- Zhiqiang Feng
- Yanlei Du
- Yuqiang Nie
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Affiliations: Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou Key Laboratory of Digestive Disease, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China, Department of Gastroenterology, The 2nd Clinical Medicine College (Shenzhen People's Hospital) of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China
Published online on: November 21, 2019 https://doi.org/10.3892/etm.2019.8226
Pages: 569-578
Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 CR749391 as a potential regulator of miR‑181a that contains four putative binding sites. Subsequent in vitro experiments in gastric cancer (GC) cells demonstrated that CR749391 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, CR749391 was observed to be downregulated in GC compared with that of normal gastric cell lines. A functional study also revealed that CR749391 depletion in normal gastric epithelial cells promoted cell viability, migration and invasion, and conferred resistance to apoptosis, whereas ectopic CR749391 overexpression had the opposite effect in GC cells and inhibited in vivo tumor growth. In addition, CR749391 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 CR749391/miR‑181a regulatory interaction and association between CR749391 and KLF6 may enhance the current understanding of GC pathogenesis, although CR749391 association with GC prognosis needs further study. The current study could provide a novel approach for lncRNA‑mediated targeted GC therapy.

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