Functional implications of miR-145/RCAN3 axis in the progression of cervical cancer

Reprod Biol. 2020 Jun;20(2):140-146. doi: 10.1016/j.repbio.2020.04.001. Epub 2020 Apr 25.

Abstract

Cervical cancer, as the second leading cause of death in women malignant tumor, is not optimistic about survival rate and late recurrence rate. RCAN3 has been reported to function in a variety of diseases, but its relationship with cervical cancer has not been reported. This study aimed to investigate whether RCAN3 contributes to the development of cervical cancer and its mechanism. RCAN3 expression was analyzed in 306 cervical cancer tissues and 13 normal healthy tissues from TCGA and GTEX databases. Kaplan-Meier analysis and Cox regression analysis were carried out to assess the potential function of RCAN3. Subsequently, the upstream regulatory miRNA of RCAN3 was predicted by bioinformatics and confirmed using dual luciferase reporter assay. CCK-8, colony formation assay, transwell assay were used for functional analysis of miR-145/RCAN3 axis in vitro. The results showed that RCAN3 was highly expressed in cervical cancer tissues, leading to poor prognosis, and could be used as a prognostic factor for cervical cancer. MiR-145 directly targeted RCAN3, which was lowly expressed in cervical cancer tissues and cell lines, and the higher the miR-145 expression, the longer the survival time of patients. Finally, from the functional experiments results we can see that miR-145 can inhibit the proliferation, migration and invasion of cervical cancer cells, but overexpression of RCAN3 can reverse miR-145-mediated inhibition. To sum up, miR-145/RCAN3 axis may serve as a potential therapeutic target to regulate the progression of cervical cancer.

Keywords: Cervical cancer; RCAN3; Target; miR-145.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / physiology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression*
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / physiology
  • Neoplasm Invasiveness / genetics
  • Prognosis
  • Transfection
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology*

Substances

  • Adaptor Proteins, Signal Transducing
  • MIRN145 microRNA, human
  • MicroRNAs
  • RCAN3 protein, human