Knockdown of COUP-TFII inhibits cell proliferation and induces apoptosis through upregulating BRCA1 in renal cell carcinoma cells

Int J Cancer. 2016 Oct 1;139(7):1574-85. doi: 10.1002/ijc.30193. Epub 2016 Jun 1.

Abstract

COUP-TFII belongs to the nuclear receptor family, which is highly expressed in many kinds of tumors. Previous studies have shown that COUP-TFII can promote tumor progression through regulating tumor angiogenesis and cell proliferation and migration of certain cancer cells. However, the function of COUP-TFII in renal cell carcinoma (RCC) is not clear. Here, we showed that clinical RCC tumor tissues showed much higher COUP-TFII expression level than adjacent normal tissues. When COUP-TFII was knocked down in RCC 769-P and 786-O cells by siRNA or shRNA-expressing lentivirus, the cell proliferation was markedly inhibited, and apoptosis increased. Moreover, the tumor growth of COUP-TFII knockdown 769-P and 786-O xenografts in nude mice was also obviously inhibited. Using qRT-PCR and Western blot, we showed that the expression of the tumor suppressor gene BRCA1 was upregulated in COUP-TFII knockdown cells. Simultaneously knockdown of BRCA1 and COUP-TFII partially rescued the inhibited cell proliferation and increased apoptosis in COUP-TFII single knockdown cells. These results indicate that COUP-TFII may play an oncogenic role in RCC, and COUP-TFII may promote tumor progression through inhibiting BRCA1.

Keywords: BRCA1; COUP-TFII; apoptosis; cell proliferation; renal cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology
  • BRCA1 Protein / biosynthesis
  • BRCA1 Protein / genetics*
  • COUP Transcription Factor II / biosynthesis
  • COUP Transcription Factor II / deficiency
  • COUP Transcription Factor II / genetics*
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Knockdown Techniques
  • Genes, BRCA1
  • Heterografts
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Up-Regulation

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • COUP Transcription Factor II
  • NR2F2 protein, human
  • RNA, Small Interfering