miR-155 regulates the proliferation and invasion of clear cell renal cell carcinoma cells by targeting E2F2

Oncotarget. 2016 Apr 12;7(15):20324-37. doi: 10.18632/oncotarget.7951.

Abstract

MicroRNAs (miRNAs) have emerged as critical modulators of carcinogenesis and tumor progression. In the present work, we sought to identify the biological function of miR-155 as well as its underlying mechanism in clear cell renal cell carcinoma (ccRCC). We examined the expression of miR-155 in clear cell RCC (ccRCC) and adjacent normal tissues and then explored the roles of miR-155 both in vitro and in vivo. The results of this analysis indicated that miR-155 activity was significantly upregulated in ccRCC tissues compared with the corresponding normal tissues. miR-155 was associated with ccRCC aggressiveness in both cell lines and clinical specimens, and a specific and inverse correlation between miR-155 and E2F2 expression was found in human ccRCC samples. Overexpression of miR-155 in 786-O cells decreased E2F2 expression while reduction of miR-155 by anti-miR-155 in ACHN cells elevated E2F2 expression. Re-expression of E2F2 in 786-O cells repressed the cell migration/invasion abilities elevated by miR-155, whereas knockdown of E2F2 in ACHN cells restored these cellular functions hampered by the miR-155 inhibitor. Using Western blot and luciferase reporter assays, we determined that E2F2 was a direct target of miR-155. Taken together, the in vitro and in vivo results demonstrate that miR-155 functions as a tumor-promoting miRNA by targeting E2F2 in ccRCC.

Keywords: E2F2; clear cell renal cell carcinoma; miR-155; proliferation and invasion.

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology*
  • Cell Movement
  • Cell Proliferation
  • E2F2 Transcription Factor / genetics
  • E2F2 Transcription Factor / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Prognosis
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • E2F2 Transcription Factor
  • E2F2 protein, human
  • MIRN155 microRNA, human
  • MicroRNAs

Supplementary concepts

  • Clear-cell metastatic renal cell carcinoma