miR-146a promotes cervical cancer cell viability via targeting IRAK1 and TRAF6

Oncol Rep. 2018 Jun;39(6):3015-3024. doi: 10.3892/or.2018.6391. Epub 2018 Apr 23.


Cervical cancer is the third most common type of cancer in women, and microRNAs play an important role in this type of cancer. The elevated expression of miR-146a is involved in the pathogenesis of cancers generally, but its role in cervical cancer has not been fully elucidated. In the present study, we assessed the expression of miR-146a in G>C polymorphisms and confirmed that the overexpression of miR-146a promoted cervical cancer cell viability. The recombinant expression plasmids pre-miR-146a-G or pre-miR-146a-C including single nucleotide polymorphisms (SNP) were successfully constructed. Pre-miR-146a-G or pre-miR-146a-C was transfected into cervical cancer cells or immortalized non-tumorigenic cells and the expression of miR-146a was evaluated by real-time PCR. The cell viability, cell-cycle analysis and apoptosis were assessed using Cell Counting Kit-8 assay (CCK-8), flow cytometry and cleaved caspase-3 protein expression, respectively. The expression of interleukin 1 receptor associated kinase 1 (IRAK1), TNF receptor-associated factor 6 (TRAF6) and cyclin D1 was assessed following the transfection with a miR-146a mimic or a negative control. The cell viability and the number of S-phase cells increased after transfection with miR-146a mimic or an IRAK1 or TRAF6 interference fragment. After transfection, IRAK1 and TRAF6 protein expression was downregulated and the expression of cyclin D1 was upregulated, however apoptosis and cleaved caspase-3 were not affected. Polymorphisms in miR-146a precursor may be linked to the expression of miR-146a and may be a potential target for cervical cancer therapy.

MeSH terms

  • 3' Untranslated Regions
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Humans
  • Interleukin-1 Receptor-Associated Kinases / genetics
  • Interleukin-1 Receptor-Associated Kinases / metabolism*
  • Intracellular Signaling Peptides and Proteins
  • MicroRNAs / genetics*
  • Polymorphism, Single Nucleotide*
  • TNF Receptor-Associated Factor 6 / genetics
  • TNF Receptor-Associated Factor 6 / metabolism*
  • Uterine Cervical Neoplasms / genetics*


  • 3' Untranslated Regions
  • Intracellular Signaling Peptides and Proteins
  • MIRN146 microRNA, human
  • MicroRNAs
  • TNF Receptor-Associated Factor 6
  • Tifab protein, human
  • IRAK1 protein, human
  • Interleukin-1 Receptor-Associated Kinases