Long non-coding RNA MALAT1 promotes tumour growth and metastasis in colorectal cancer through binding to SFPQ and releasing oncogene PTBP2 from SFPQ/PTBP2 complex

Br J Cancer. 2014 Aug 12;111(4):736-48. doi: 10.1038/bjc.2014.383. Epub 2014 Jul 15.

Abstract

Background: Metastasis associated with lung adenocarcinoma transcript-1 (MALAT1) is a functional long non-coding RNA (lncRNA), which is highly expressed in several tumours, including colorectal cancer (CRC). Its biological function and mechanism in the prognosis of human CRC is still largely under investigation.

Methods: This study aimed to investigate the new effect mechanism of MALAT1 on the proliferation and migration of CRC cells in vitro and in vivo, and detect the expression of MALAT1, SFPQ (also known as PSF (PTB-associated splicing factor)), and PTBP2 (also known as PTB (polypyrimidine-tract-binding protein)) in CRC tumour tissues, followed by correlated analysis with clinicopathological parameters.

Results: We found that overexpression of MALAT1 could promote cell proliferation and migration in vitro, and promote tumour growth and metastasis in nude mice. The underlying mechanism was associated with tumour suppressor gene SFPQ and proto-oncogene PTBP2. In CRC, MALAT1 could bind to SFPQ, thus releasing PTBP2 from the SFPQ/PTBP2 complex. In turn, the increased SFPQ-detached PTBP2 promoted cell proliferation and migration. SFPQ critically mediated the regulatory effects of MALAT1. Moreover, in CRC tissues, MALAT1 and PTBP2 were overexpressed, both of which were associated closely with the invasion and metastasis of CRC. However, the SFPQ showed unchanged expression either in CRC tissues or adjacent normal tissues.

Conclusions: Our findings implied that MALAT1 might be a potential predictor for tumour metastasis and prognosis. Furthermore, the interaction between MALAT1 and SFPQ could be a novel therapeutic target for CRC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Female
  • HEK293 Cells
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Multiprotein Complexes / metabolism
  • Neoplasm Transplantation
  • Nerve Tissue Proteins / metabolism*
  • Oncogenes
  • PTB-Associated Splicing Factor
  • Polypyrimidine Tract-Binding Protein / metabolism*
  • Protein Binding
  • Protein Transport
  • RNA, Long Noncoding / physiology*
  • RNA-Binding Proteins / metabolism*

Substances

  • MALAT1 long non-coding RNA, human
  • Multiprotein Complexes
  • Nerve Tissue Proteins
  • PTB-Associated Splicing Factor
  • PTBP2 protein, human
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • Polypyrimidine Tract-Binding Protein