Circular RNA hsa_circ_0007444 inhibits ovarian cancer progression through miR-23a-3p/DICER1 axis

Acta Biochim Biophys Sin (Shanghai). 2023 Apr 13;55(4):574-586. doi: 10.3724/abbs.2023052.

Abstract

Ovarian cancer is the second leading cause of death in women with gynecological malignancy in China. Circular RNAs are a class of noncoding regulatory RNAs reported to be involved in cancer development and progression. Previous studies, including our own, have indicated that hsa_circ_0007444 is downregulated in ovarian cancer tissues. This study aims to elucidate the function and mechanism of hsa_circ_0007444 in ovarian cancer progression. The expression of hsa_circ_0007444 is determined by quantitative real-time PCR (qRT-PCR). Cell proliferation, invasion, migration and apoptosis are examined by cell counting-kit 8 (CCK-8), transwell and flow cytometry assays. Tumor growth and metastasis are assessed in vivo using Balb/c nude mouse xenograft model and tail vein injection model. And the mechanism of action of hsa_circ_0007444 is analysed by RNA-binding protein immunoprecipitation (RIP), luciferase reporter and rescue assays. hsa_circ_0007444 is downregulated in ovarian cancer tissues and cell lines compared with that in normal ovarian tissues and normal epithelial cell line. Gain- and loss-of-function results indicate that hsa_circ_0007444 inhibits cell proliferation, invasion, migration and increases cell apoptosis of ovarian cancer cells in vitro, and inhibits tumor growth and lung metastasis in vivo. Mechanistically, hsa_circ_0007444 can interact with AGO2 and sponge miR-23a-3p, thereby upregulating DICER1 expression, which is an important tumor suppressor in ovarian cancer. And miR-23a-3p mimics can rescue the inhibitory effect of hsa_circ_0007444 on ovarian cancer cell proliferation, invasion and migration. Therefore, hsa_circ_0007444 can inhibit ovarian cancer progression through the hsa_circ_0007444/miR-23a-3p/DICER1 axis.

Keywords: DICER1; hsa_circ_0007444; miR-23a-3p; ovarian cancer; progression.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • DEAD-box RNA Helicases / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms*
  • Mice
  • MicroRNAs* / genetics
  • Ovarian Neoplasms* / genetics
  • RNA, Circular / genetics
  • Ribonuclease III

Substances

  • DEAD-box RNA Helicases
  • DICER1 protein, human
  • MicroRNAs
  • Ribonuclease III
  • RNA, Circular
  • MIRN23a microRNA, human

Grants and funding

This work was supported by the grants from the National Natural Science Foundation of China (No. 81902651) and the 333 Project of Jiangsu Province (to X.J.).