MicroRNA-10a suppresses cell metastasis by targeting BDNF and predicted patients survival in renal cell carcinoma

J BUON. 2021 Jan-Feb;26(1):250-258.

Abstract

Purpose: Renal cell carcinoma (RCC) is the most common renal neoplasm and accounts for 3% of all cancers. Increasing studies reported that miR-10a, acting as tumor suppressor, was downregulated in several cancers. It has been reported that the proteins encoded by Brain-Derived Neutrophic Factor (BDNF) were members of the nerve growth factor family, and could promote neuronal survival in the adult brain. The purpose of this study was to explore how miR-10a worked in RCC on the metastasis.

Methods: The expression level of miR-10a and BDNF were calculated using RT-PCR and western blot. Transwell assay was utilized to evaluate the invasive ability. Kaplan-Meier method along with log-rank test were applied to evaluate the 5-year overall survival of RCC patients.

Results: miR-10a was significantly downregulated and BDNF was upregulated in RCC tissues and cell lines A498 and 786-O. The expression of miR-10a had a reverse correlation with BDNF in RCC tissues. Overexpression of miR-10a or interference of BDNF inhibited the invasion and epithelial-mesenchymal transition (EMT) of A498 cells. What's more, BDNF was demonstrated to be a target gene of miR-10a and miR-10a could mediate the expression of BDNF in RCC. In addition, low expression of miR-10a or overexpression of BDNF predicted poor prognosis of RCC patients.

Conclusion: Our results indicated that miR-10a inhibited the invasion and EMT by regulating BDNF in RCC. The newly identified miR-10a/BDNF axis provides novel insight into the pathogenesis of RCC.

MeSH terms

  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Male
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Survival Analysis
  • Transfection

Substances

  • Brain-Derived Neurotrophic Factor
  • MIRN10 microRNA, human
  • MicroRNAs
  • BDNF protein, human