Hypoxia-induced miR-9 expression promotes ovarian cancer progression via activating PI3K/AKT/mTOR/GSK3β signaling pathway

Neoplasma. 2023 Apr;70(2):216-228. doi: 10.4149/neo_2023_221103N1079. Epub 2023 Mar 24.


Ovarian cancer (OC) is one of the most prevalent malignant tumors affecting women's life and health. Since OC has a poor prognosis due to extensive metastasis, there is a need to explore a new mechanism of OC metastasis. microRNAs (miRs) are single-stranded, non-coding RNAs. miR-9 has been reported to promote cancer and may provide a new strategy for OC diagnosis. The purpose of this study was to examine the function and underlying mechanism of miR-9 in OC. RT-qPCR was used to assess miR-9 expression levels. Transwell assays were used to determine the number of migrating and invading OC cells. The protein expression levels of the PI3K/AKT/mTOR/GSK3β signaling pathway were examined using western blotting. The results informed that, when compared to normal ovarian tissues, miR-9 was remarkably expressed in OC tissues, and hypoxia might lead to overexpression of miR-9-5p while inhibiting miR-9 notably suppressed the migrating and invading cell numbers in OC cells. In vivo, miR-9-5p knockdown inhibited tumor growth in a subcutaneous nude mice model of SKOV3 cells. Our findings suggest that miR-9 could be an underlying oncogene in OC, opening up new avenues for OC diagnosis and treatment of OC by targeting miR-9.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Ovarian Neoplasms* / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism


  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • Glycogen Synthase Kinase 3 beta
  • MicroRNAs
  • TOR Serine-Threonine Kinases
  • MTOR protein, human
  • MIRN9 microRNA, mouse