The Long Noncoding RNA MALAT-1 Is Highly Expressed in Ovarian Cancer and Induces Cell Growth and Migration

PLoS One. 2016 May 26;11(5):e0155250. doi: 10.1371/journal.pone.0155250. eCollection 2016.

Abstract

Background: Metastasis associated in lung adenocarcinoma transcript-1 (MALAT-1) is overexpressed during cancer progression and promotes cell migration and invasion in many solid tumors. However, its role in ovarian cancer remains poorly understood.

Methods: Expressions of MALAT-1 were detected in 37 normal ovarian tissues and 45 ovarian cancer tissues by reverse transcription polymerase chain reaction (RT-PCR). Cell proliferation was observed by CCK-8 assay; Flow cytometry was used to measure cell cycle and apoptosis; Cell migration was detected by transwell migration and invasion assay. In order to evaluate the function of MALAT-1, shRNA combined with DNA microarray and Functional enrichment analysis were performed to determine the transcriptional effects of MALAT-1 silencing in OVCAR3 cells. RNA and protein expression were measured by qRT-PCR and Western blotting, respectively.

Results: We found that upregulation of MALAT-1 mRNA in ovarian cancer tissues and enhanced MALAT-1 expression was associated with FIGO stage. Knockdown of MALAT-1 expression in OVCAR3 cells inhibited cell proliferation, migration, and invasion, leading to G0/G1 cell cycle arrest and apoptosis. Overexpressed MALAT-1 expression in SKOV3 cells promoted cell proliferation, migration and invasion. Downregulation of MALAT-1 resulted in significant change of gene expression (at least 2-fold) in 449 genes, which regulate proliferation, cell cycle, and adhesion. As a consequence of MALAT-1 knockdown, MMP13 protein expression decreased, while the expression of MMP19 and ADAMTS1 was increased.

Conclusions: The present study found that MALAT-1 is highly expressed in ovarian tumors. MALAT-1 promotes the growth and migration of ovarian cancer cells, suggesting that MALAT-1 may be an important contributor to ovarian cancer development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAMTS1 Protein / biosynthesis
  • Adult
  • Apoptosis
  • Cell Cycle*
  • Cell Line, Tumor
  • Cell Movement*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • Humans
  • Matrix Metalloproteinase 13 / biosynthesis
  • Matrix Metalloproteinases, Secreted / biosynthesis
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Proteins / biosynthesis
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • RNA, Long Noncoding / biosynthesis*
  • RNA, Neoplasm / biosynthesis*

Substances

  • MALAT1 long non-coding RNA, human
  • Neoplasm Proteins
  • RNA, Long Noncoding
  • RNA, Neoplasm
  • ADAMTS1 Protein
  • ADAMTS1 protein, human
  • MMP13 protein, human
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinases, Secreted
  • matrix metalloproteinase 19

Grants and funding

This study was supported by grants from the Science and Information Technology Agency of Guangzhou (No. 2010GNE00221) and the Mechanism Study of MALAT1 Promote Invasion and Metastasis of Ovarian Cancer by Targeted Regulating STAT3 Signaling Pathway (No. 2014A020212517).