Nuclear factor-κB-dependent microRNA-130a upregulation promotes cervical cancer cell growth by targeting phosphatase and tensin homolog

Arch Biochem Biophys. 2016 May 15:598:57-65. doi: 10.1016/j.abb.2016.03.019. Epub 2016 Apr 1.

Abstract

Nuclear factor-κB (NF-κB) may activate a series of gene transcription control cellular signaling pathways whose products are components in a wide range of biological processes. MicroRNAs, a group of non-coding endogenous ones, may regulate gene expression and plays specific roles in tumorigenesis. Using human cervical cancer cell lines, we explored whether NF-κB regulates the expression of microRNA-130a (miR-130a) through binding elements in the miR-130a promoter region. We found that miR-130a accelerates cervical cancer cell proliferation by targeting the phosphatase and tensin homolog on chromosome 10 (PTEN). Further, NF-κB activates both HeLa and CaSki cell growth by upregulating miR-130a. In addition, by targeting PTEN 3' untranslated region, miR-130a might increase cell growth and initiate protein kinase B (AKT) pathway activation. Lastly, PTEN protein was upregulated in response to NF-κB overexpression and downregulated in response to NF-κB inhibition. Compared to total AKT protein level, p-AKT was downregulated by NF-κB overexpression while upregulated by NF-κB inhibition, indicating PTEN pathway activated and affected by NF-κB. Taken together, our findings shed new light on the NF-κB/miR-130a/PTEN pathway in cervical cancer and add new insight regarding the carcinogenesis of cervical cancer.

Keywords: AKT; Cervical cancer; NF-κB; PTEN; Tumorigenesis; miR-130a.

MeSH terms

  • 3' Untranslated Regions
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HeLa Cells
  • Humans
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Neoplasm / biosynthesis*
  • RNA, Neoplasm / genetics
  • Signal Transduction
  • Up-Regulation*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology

Substances

  • 3' Untranslated Regions
  • MIRN130 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • RNA, Neoplasm
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human