Long Non-Coding RNA BANCR Promotes Endometrial Cancer Cell Proliferation and Invasion by Regulating MMP2 and MMP1 via ERK/MAPK Signaling Pathway

Cell Physiol Biochem. 2016;40(3-4):644-656. doi: 10.1159/000452577. Epub 2016 Nov 30.

Abstract

Background/aims: Microarray screening had found BRAF-activated non-coding RNA (BANCR) was significantly upregulated in type 1 endometrial cancer (EC). This study aimed to assess the potential role of long non-coding RNA (lncRNA) BANCR in the pathogenesis and progression of type 1 EC.

Methods: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to confirm the expression of BANCR in type 1 EC tissue, and analyze its clinical significance. In vitro, RNA interference (siRNA) was used to investigate the biological role of BANCR in type 1 EC.

Results: qRT-PCR revealed that the expression of lncRNA BANCR was higher in type 1 EC (P<0.01). BANCR expression was significantly correlated with FIGO stage, pathological grade, myometrial invasion, and lymph node metastasis. The expression of BANCR was significantly correlated with that of MMP2/MMP1. In vitro, knockdown of BANCR significantly suppressed proliferation, migration, and invasion of Ishikawa and HEC-1A cells, and significantly inhibited the ERK/MAPK signaling pathway that decreased MMP2 and MMP1 expression.

Conclusion: BANCR is highly expressed in type 1 EC tissue and promotes EC-cell proliferation, migration, and invasion by activating ERK/MAPK signaling pathway that regulates MMP2/MMP1 expression. BANCR is expected to become a prognostic marker and therapeutic target in type 1 EC.

MeSH terms

  • Blotting, Western
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cyclin D1 / metabolism
  • Endometrial Neoplasms / enzymology*
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MAP Kinase Signaling System*
  • Matrix Metalloproteinase 1 / genetics*
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 2 / genetics*
  • Matrix Metalloproteinase 2 / metabolism
  • Middle Aged
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / metabolism
  • Transfection

Substances

  • BANCR long non-coding RNA, human
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Cyclin D1
  • Matrix Metalloproteinase 2
  • MMP1 protein, human
  • Matrix Metalloproteinase 1