MiR-155-5p inhibits PDK1 and promotes autophagy via the mTOR pathway in cervical cancer

Int J Biochem Cell Biol. 2018 Jun;99:91-99. doi: 10.1016/j.biocel.2018.04.005. Epub 2018 Apr 5.

Abstract

Cervical cancer is one of the most common malignant tumors and the leading cause of cancer-related mortality in women. Persistent cervical infection by high-risk human papillomavirus (hrHPV) is related to cervical cancer. MicroRNAs could regulate autophagy caused by viral infection. The aim of the present study was to investigate the regulation of autophagy by miR-155-5p in cervical cancer. In HPV+ human cervical lesion tissues, miR-155-5p expression was found to be markedly decreased. Compared to C33A cancer cells (HPV-), the miR-155-5p expression was significantly lower in Siha and HeLa cells (HPV+), which are both hrHPV positive. The level of autophagy was higher in C33A cells than in Siha and HeLa cells. In addition, in C33A, Siha and HeLa cervical cancer cells, miR-155-5p overexpression promoted autophagy, whereas miR-155-5p downregulation had the opposite effects. Furthermore, miR-155-5p downregulation suppressed LC3 and promoted P62 protein expression in C33A cells through promoting the PDK1/mTOR pathway, whereas miR-155-5p overexpression recovered LC3 and suppressed P62 protein expression by suppressing PDK1/mTOR signaling. Taken together, our results indicate the importance of miR-155-5p in cervical cancer cells and suggest a novel mechanism of hrHPV in promoting cervical lesions.

Keywords: Cervical cancer; High-risk human papillomavirus; MicroRNA; Pyruvate dehydrogenase kinase 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MicroRNAs / genetics*
  • Prognosis
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Signal Transduction
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • MIRN155 microRNA, human
  • MicroRNAs
  • PDK1 protein, human
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • MTOR protein, human
  • Protein Serine-Threonine Kinases
  • TOR Serine-Threonine Kinases