The mechanisms involved in miR-9 regulated apoptosis in cervical cancer by targeting FOXO3

Biomed Pharmacother. 2018 Jun:102:626-632. doi: 10.1016/j.biopha.2018.03.019. Epub 2018 Apr 5.

Abstract

As a seriously global health problem, cervical cancer is a great risk to women which threatens their lives. Approximately 30% patients who received definitive treatment may fail to recover from this disease. Accordingly, there is an imperatively need to explore alternative therapeutic approaches for this disease. Several studies have revealed that miR-9 was a critical regulator during cervical cancer growth. Here, we reported that the miR-9 was overexpressed in cervical tumor tissue and exerted a promoting effect on human cervical cancer cell (SiHa) growth. Both in vitro and in vivo experiments confirmed that miR-9 could stimulate the proliferation and migration of SiHa cells. In contrast, inhibition of miR-9 induced apoptosis in SiHa cells. In addition, dual luciferase reporter system assay verified that there was a strong target relationship between miR-9 and FOXO3. Result of western blot assay showed that the inhibition of miR-9 increased the expression of FOXO3. Moreover, miR-9 regulated FOXO3 downstream proteins Bax, Bcl-2 and p-Akt expressions, which suggesting that miR-9 was involved in the SiHa cells apoptosis. In conclusion, our results suggest that the inhibition of miR-9 could induce apoptosis in cervical cancer by targeting FOXO3 and presented a potential molecular target for the treatment of cervical cancer patients.

Keywords: Akt; Apoptosis; Cervical cancer; FOXO3; miR-9.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation / genetics
  • Female
  • Forkhead Box Protein O3 / genetics
  • Forkhead Box Protein O3 / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Survival Rate
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / mortality
  • Uterine Cervical Neoplasms / pathology*
  • bcl-2-Associated X Protein / metabolism

Substances

  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • MIRN92 microRNA, human
  • MicroRNAs
  • bcl-2-Associated X Protein
  • Proto-Oncogene Proteins c-akt