Long non-coding RNA LINC01133 inhibits epithelial-mesenchymal transition and metastasis in colorectal cancer by interacting with SRSF6

Cancer Lett. 2016 Oct 1;380(2):476-484. doi: 10.1016/j.canlet.2016.07.015. Epub 2016 Jul 18.

Abstract

Long non-coding RNAs (lncRNAs) play crucial roles in many biological and pathological processes, including tumor metastasis. Here we reported a novel lncRNA, LINC01133 that was downregulated by TGF-β, which could inhibit epithelial-mesenchymal transition (EMT) and metastasis in colorectal cancer (CRC) cells. An alternative splicing factor SRSF6 was identified to directly interact with LINC01133, and SRSF6 promoted EMT and metastasis in CRC cells independent of LINC01133 And we confirmed that the EMT process was regulated by LINC01133 in CRC cells dependent on the presence of SRSF6. The observation for LINC01133 to inhibit metastasis was also verified in vivo. Moreover clinical data showed that the LINC01133 expression was positively correlated with E-cadherin, and negatively correlated with Vimentin, and there was a robust association of low LIINC01133 expression in tumors with poor survival in CRC samples. These data suggest that LINC01133 inhibits the EMT and metastasis by directly binding to SRSF6 as a target mimic, and may serve as a prognostic biomarker and an effective target for anti-metastasis therapies for CRC.

Keywords: Colorectal cancer; EMT; Metastasis; SRSF6; lncRNA.

MeSH terms

  • Animals
  • Antigens, CD
  • Cadherins / metabolism
  • Cell Movement*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Epithelial-Mesenchymal Transition*
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / secondary
  • Lymphatic Metastasis
  • Mice, Inbred NOD
  • Mice, SCID
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • RNA Interference
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Serine-Arginine Splicing Factors / genetics
  • Serine-Arginine Splicing Factors / metabolism*
  • Signal Transduction
  • Time Factors
  • Transfection
  • Tumor Burden
  • Vimentin / metabolism

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • Phosphoproteins
  • RNA, Long Noncoding
  • SRSF6 protein, human
  • Vimentin
  • long non-coding RNA LINC01133, human
  • Serine-Arginine Splicing Factors