BANF1 is downregulated by IRF1-regulated microRNA-203 in cervical cancer

PLoS One. 2015 Feb 6;10(2):e0117035. doi: 10.1371/journal.pone.0117035. eCollection 2015.

Abstract

MicroRNAs (miRNAs) play important roles in various biological processes and are closely associated with the development of cancer. In fact, aberrant expression of miRNAs has been implicated in numerous cancers. In cervical cancer, miR-203 levels are decreased, although the cause of this aberrant expression remains unclear. In this study, we investigate the molecular mechanisms regulating miR-203 gene transcription. We identify the miR-203 transcription start site by 5' rapid amplification of cDNA ends and subsequently identify the miR-203 promoter region. Promoter analysis revealed that IRF1, a transcription factor, regulates miR-203 transcription by binding to the miR-203 promoter. We also demonstrate that miR-203 targets the 3' untranslated region of BANF1, thus downregulating its expression, whereas miR-203 expression is driven by IRF1. MiR-203 is involved in cell cycle regulation and overexpression of miR-203 suppresses cervical cancer cell proliferation, colony formation, migration and invasion. The inhibitory effect of miR-203 on the cancer cells is partially mediated by downregulating its target, BANF1, since knockdown of BANF1 also suppresses colony formation, migration and invasion.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Down-Regulation*
  • Female
  • HeLa Cells
  • Humans
  • Interferon Regulatory Factor-1 / chemistry
  • Interferon Regulatory Factor-1 / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic
  • RNA, Small Interfering / metabolism
  • Sequence Alignment
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology

Substances

  • 3' Untranslated Regions
  • BANF1 protein, human
  • DNA-Binding Proteins
  • IRF1 protein, human
  • Interferon Regulatory Factor-1
  • MIRN203 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Small Interfering
  • Transcription Factors