LncRNA-ATB mediated E-cadherin repression promotes the progression of colon cancer and predicts poor prognosis

J Gastroenterol Hepatol. 2016 Mar;31(3):595-603. doi: 10.1111/jgh.13206.

Abstract

Background: Long non-coding RNA-activated by TGF-β (lncRNA-ATB) promotes the invasion-metastasis cascade in hepatocellular carcinoma via downregulating E-cadherin (E-cad) and inducing epithelial-to- mesenchymal transition (EMT) and is clinically significant in human colon cancer. However, its molecular mechanisms in colon cancer progression remain unclear. This study aimed to elucidate the role of lncRNA-ATB and its clinical value in colon cancer.

Methods: Expression levels of lncRNA-ATB in colon cancer tissues and colon cancer cell lines were evaluated using quantitative real-time polymerase chain reaction. The clinicopathological significance and prognostic value of lncRNA-ATB were investigated, and roles of lncRNA-ATB in regulating E-cad and other EMT-related markers expression and colon cancer progression were evaluated in vitro. Expression levels of lncRNA-ATB and E-cad in human plasma were evaluated.

Results: Long non-coding RNA-activated by TGF-β was upregulated in colon cancer tissues compared with adjacent mucosa (P < 0.001). LncRNA-ATB levels were also higher in metastatic cancer tissues (P < 0.001). Among the three highly invasive colon cancer cell lines, lncRNA-ATB levels were relatively higher with concurrent low levels of E-cad compared with levels in the three low-invasive cell lines. LncRNA-ATB expression correlated with pN stage (P < 0.01) and American Joint Committee on Cancer stage (P < 0.01). Striking differences were observed in overall survival and disease-free survival in cases with both high lncRNA-ATB expression and low E-cad expression. Reduction of lncRNA-ATB increased expression of epithelial markers E-cad, ZO-1, and decreased expression of mesenchymal markers ZEB1 and N-cadherin (N-cad), and significantly influenced colon cancer cell progression. Plasma lncRNA-ATB was upregulated in colon cancer patients one month after surgery (P < 0.05).

Conclusions: Long non-coding RNA-activated by TGF-β may act on colon tumorigenesis by suppressing E-cad expression and promoting EMT process, and lncRNA-ATB inhibition may provide a promising therapeutic option for suppressing colon cancer progression.

Keywords: E-cadherin; TGF-β; colon cancer; lncRNA-ATB; oncogene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / genetics*
  • Cadherins / metabolism*
  • Carcinogenesis / genetics*
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / mortality
  • Colonic Neoplasms / pathology*
  • Colonic Neoplasms / therapy
  • Disease Progression
  • Down-Regulation
  • Female
  • Gene Expression / genetics*
  • Humans
  • Male
  • Molecular Targeted Therapy
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • RNA, Long Noncoding / metabolism
  • RNA, Long Noncoding / physiology*
  • Real-Time Polymerase Chain Reaction
  • Survival Rate
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / physiology*
  • Up-Regulation

Substances

  • Cadherins
  • RNA, Long Noncoding
  • Transforming Growth Factor beta