A miRNA-7704/IL2RB/AKT feedback loop regulates tumorigenesis and chemoresistance in ovarian cancer

Exp Cell Res. 2024 Apr 15;437(2):114012. doi: 10.1016/j.yexcr.2024.114012. Epub 2024 Mar 31.

Abstract

Ovarian cancer is one of the most common gynecological tumors worldwide. Despite the availability of multiple treatments for ovarian cancer, its resistance to chemotherapy remains a significant challenge. miRNAs play crucial roles in the initiation and progression of cancer by affecting processes such as differentiation, proliferation, and chemoresistance. According to microarray and qPCR analyses, miR-7704 is significantly downregulated in cisplatin-resistant cells compared to parental cells. In this study, we found that miR-7704 inhibited the proliferation and promoted cisplatin sensitivity of ovarian cancer cells in vitro and in vivo. Moreover, ectopic expression of miR-7704 had the same effect as IL2RB knockdown. Further mechanistic studies revealed that miR-7704 played an inhibitory role by regulating IL2RB expression to inactivate the AKT signaling pathway. Furthermore, IL2RB reversed the miR-7704 mediated resistance to cisplatin in ovarian cancer. Based on these findings, miR-7704 and IL2RB show the potential as novel therapeutic targets for ovarian cancer.

MeSH terms

  • Carcinogenesis
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm
  • Feedback
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interleukin-2 Receptor beta Subunit / metabolism
  • Interleukin-2 Receptor beta Subunit / pharmacology
  • Interleukin-2 Receptor beta Subunit / therapeutic use
  • MicroRNAs* / metabolism
  • Ovarian Neoplasms* / pathology
  • Proto-Oncogene Proteins c-akt / metabolism

Substances

  • MicroRNAs
  • Cisplatin
  • Proto-Oncogene Proteins c-akt
  • IL2RB protein, human
  • Interleukin-2 Receptor beta Subunit