Rsf-1 is overexpressed in non-small cell lung cancers and regulates cyclinD1 expression and ERK activity

Biochem Biophys Res Commun. 2012 Mar 30;420(1):6-10. doi: 10.1016/j.bbrc.2012.02.095. Epub 2012 Feb 24.

Abstract

Rsf-1 (HBXAP) was recently reported to be overexpressed in various cancers and associated with the malignant behavior of cancer cells. However, the expression of Rsf-1 in primary lung cancer and its biological roles in non-small cell lung cancer (NSCLC) have not been reported. The molecular mechanism of Rsf-1 in cancer aggressiveness remains ambiguous. In the present study, we analyzed the expression pattern of Rsf-1 in NSCLC tissues and found that Rsf-1 was overexpressed at both the mRNA and protein levels. There was a significant association between Rsf-1 overexpression and TNM stage (p=0.0220) and poor differentiation (p=0.0013). Furthermore, knockdown of Rsf-1 expression in H1299 and H460 cells with high endogenous Rsf-1 expression resulted in a decrease of colony formation ability and inhibition of cell cycle progression. Rsf-1 knockdown also induced apoptosis in these cell lines. Further analysis showed that Rsf-1 knockdown decreased cyclin D1 expression and phospho-ERK levels. In conclusion, Rsf-1 is overexpressed in NSCLC and contributes to malignant cell growth by cyclin D1 and ERK modulation, which makes Rsf-1 a candidate therapeutic target in lung cancer.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin D1 / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Trans-Activators / biosynthesis*
  • Trans-Activators / genetics

Substances

  • Nuclear Proteins
  • RNA, Messenger
  • RSF1 protein, human
  • Trans-Activators
  • Cyclin D1
  • Extracellular Signal-Regulated MAP Kinases