LncRNA-PAGBC acts as a microRNA sponge and promotes gallbladder tumorigenesis

EMBO Rep. 2017 Oct;18(10):1837-1853. doi: 10.15252/embr.201744147. Epub 2017 Sep 8.

Abstract

Long noncoding RNAs (lncRNAs) play roles in the development and progression of many cancers; however, the contributions of lncRNAs to human gallbladder cancer (GBC) remain largely unknown. In this study, we identify a group of differentially expressed lncRNAs in human GBC tissues, including prognosis-associated gallbladder cancer lncRNA (lncRNA-PAGBC), which we find to be an independent prognostic marker in GBC Functional analysis indicates that lncRNA-PAGBC promotes tumour growth and metastasis of GBC cells. More importantly, as a competitive endogenous RNA (ceRNA), lncRNA-PAGBC competitively binds to the tumour suppressive microRNAs miR-133b and miR-511. This competitive role of lncRNA-PAGBC is required for its ability to promote tumour growth and metastasis and to activate the AKT/mTOR pathway. Moreover, lncRNA-PAGBC interacts with polyadenylate binding protein cytoplasmic 1 (PABPC1) and is stabilized by this interaction. This work provides novel insight on the molecular pathogenesis of GBC.

Keywords: PAGBC; ceRNA; gallbladder cancer; lncRNA; prognosis.

MeSH terms

  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Gallbladder / physiopathology*
  • Gallbladder Neoplasms / genetics*
  • Gallbladder Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Neoplasm Metastasis
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding / genetics*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • MIRN133 microRNA, human
  • MIRN511 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • MTOR protein, human
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases