Long Noncoding RNA LINC01234 Functions as a Competing Endogenous RNA to Regulate CBFB Expression by Sponging miR-204-5p in Gastric Cancer

Clin Cancer Res. 2018 Apr 15;24(8):2002-2014. doi: 10.1158/1078-0432.CCR-17-2376. Epub 2018 Jan 31.

Abstract

Purpose: Long noncoding RNAs (lncRNAs) have emerged as important regulators in a variety of human diseases, including cancers. However, the overall biological roles and clinical significance of most lncRNAs in gastric carcinogenesis are not fully understood. We investigated the clinical significance, biological function, and mechanism of LINC01234 in gastric cancer.Experimental Design: First, we analyzed LINC01234 alterations in gastric cancerous and noncancerous tissues through an analysis of sequencing data obtained from The Cancer Genome Atlas. Next, we evaluated the effect of LINC01234 on the gastric cancer cell proliferation and apoptosis, and its regulation of miR-204-5p by acting as a competing endogenous RNA (ceRNA). The animal model was used to support the in vitro experimental findings.Results: We found that LINC01234 expression was significantly upregulated in gastric cancer tissues and was associated with larger tumor size, advanced TNM stage, lymph node metastasis, and shorter survival time. Furthermore, knockdown of LINC01234-induced apoptosis and growth arrest in vitro and inhibited tumorigenesis in mouse xenografts. Mechanistic investigations indicated that LINC01234 functioned as a ceRNA for miR-204-5p, thereby leading to the derepression of its endogenous target core-binding factor β (CBFB).Conclusions: LINC01234 is significantly overexpressed in gastric cancer, and LINC01234-miR-204-5p-CBFB axis plays a critical role in gastric cancer tumorigenesis. Our findings may provide a potential new target for gastric cancer diagnosis and therapy. Clin Cancer Res; 24(8); 2002-14. ©2018 AACR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Apoptosis / genetics
  • Biomarkers, Tumor
  • Carcinogenesis / genetics
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Core Binding Factor beta Subunit / genetics*
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • Heterografts
  • Humans
  • Kaplan-Meier Estimate
  • Mice
  • MicroRNAs / genetics*
  • Prognosis
  • RNA Interference*
  • RNA, Long Noncoding / genetics*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology

Substances

  • 3' Untranslated Regions
  • Biomarkers, Tumor
  • CBFB protein, human
  • Core Binding Factor beta Subunit
  • MIRN204 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding