MicroRNA 1301 inhibits cisplatin resistance in human ovarian cancer cells by regulating EMT and autophagy

Eur Rev Med Pharmacol Sci. 2020 Feb;24(4):1688-1696. doi: 10.26355/eurrev_202002_20343.

Abstract

Objective: Ovarian cancer is prone to chemoresistance, leading to poor outcomes in patients. MicroRNA 1301 plays a regulatory role in multiple tumors. However, whether microRNA 1301 regulates cisplatin resistance in ovarian cancer cells remains unclear.

Materials and methods: The ovarian cancer SKOV3 cell line and the human ovarian cancer cisplatin-resistant strain cell SKOV3/DDP were cultured in vitro and microRNA1301 expression was analyzed by Real time PCR. MicroRNA1301 mimics and microRNA 1301 were transfected into SKOV3/DDP, respectively followed by analysis of cell proliferation by MTT assay, cell invasion, expression of autophagy genes ATG5 and Beclin1 and EMT-related transcription factors Snail and Slug by Real time PCR, expression of NF-κB and E-cadherin and N-cadherin by Western blot.

Results: MicroRNA 1301 expression was significantly increased in SKOV3/DDP cells compared with that in SKOV3 cells (p<0.05). MicroRNA1301 mimics transfection into SKOV3/DDP up-regulated microRNA1301 expression, promoted cell proliferation, and invasion, inhibited ATG5 and Beclin1 expression, and promoted Snail and Slug expression, decreased E-cadherin expression and increased N-cadherin and NF-κB expression, compared with the control group, the differences were statistically significant (p<0.05). MicroRNA1301 inhibitor transfection into SKOV3/DDP cells could down-regulate the expression of microRNA1301 and significantly reversed the above changes. Compared with the control group, differences were statistically significant (p<0.05).

Conclusions: Targeting microRNA1301 can inhibit the proliferation of cisplatin-resistant cells and the development of EMT in human ovarian cancer cells by inhibiting the NF-κB signaling pathway, thereby inhibiting the occurrence and development of drug-resistant ovarian cancer.

MeSH terms

  • Antigens, CD / metabolism
  • Antineoplastic Agents*
  • Autophagy
  • Autophagy-Related Protein 5 / genetics
  • Beclin-1 / genetics
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Cisplatin*
  • Drug Resistance, Neoplasm / genetics*
  • Epithelial-Mesenchymal Transition
  • Female
  • Humans
  • MicroRNAs / genetics*
  • NF-kappa B / metabolism
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Snail Family Transcription Factors / genetics

Substances

  • ATG5 protein, human
  • Antigens, CD
  • Antineoplastic Agents
  • Autophagy-Related Protein 5
  • Beclin-1
  • CDH2 protein, human
  • Cadherins
  • MIRN1301 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Cisplatin