miR-1293 Suppresses Tumor Malignancy by Targeting Hydrocyanic Oxidase 2: Therapeutic Potential of a miR-1293/Hydrocyanic Oxidase 2 Axis in Renal Cell Carcinoma

Cancer Biother Radiopharm. 2020 Jun;35(5):377-386. doi: 10.1089/cbr.2019.2957. Epub 2020 Jan 22.

Abstract

Renal cell carcinoma (RCC) is a common cancer, and extensive research suggests that microRNA may play an important role in the progression of RCC. The emphasis of this article was to reveal the function and mechanism of microRNA-1293(miR-1293) in the development of RCC tumors. First, the authors carried out bioinformatics analysis. The differential expression of miR-1293 in RCC tumor and normal cells was analyzed using the data from The Cancer Genome Atlas database, and Kaplan-Meier survival analysis was carried out to test the survival rate. Subsequently, the miR-1293 expression in RCC cell lines was examined by quantitative real-time PCR. Then Cell counting kit-8 and Transwell assays were executed to detect the function of miR-1293 in RCC. Bioinformatics prediction, western blotting, and dual-luciferase reporter assay were set to check the target gene of miR-1293. Finally, they conducted rescue experiments to verify whether the regulation of miR-1293 on the biological function of RCC cells was achieved by regulating hydrocyanic oxidase 2 (HAO2). Bioinformatics results showed that miR-1293 was highly expressed in RCC, and the miR-1293 high-expression group showed a lower survival rate than the miR-1293 low-expression group, which suggested that the high expression of miR-1293 was related to unfavorable prognosis in RCC. Subsequent assays evidenced that upregulation of miR-1293 expression significantly increased the cell viability and promoted cell migration and invasion in RCC. Silencing miR-1293 expression showed opposite results. Furthermore, HAO2 was confirmed to be a direct target gene of miR-1293 by dual-luciferase reporter assay, and miR-1293 negatively regulated the expression of HAO2. Moreover, rescue experiments evidenced that miR-1293 reduced the cell viability, invasion, and migration of RCC by regulating HAO2. In sum, miR-1293 can regulate the viability, invasion, and migration of RCC tumor cells by targeting HAO2, suggesting that miR-1293 can be used as a new biomarker for clinical treatment of RCC.

Keywords: HAO2; RCC; miR-1293; target.

MeSH terms

  • Alcohol Oxidoreductases / genetics*
  • Antineoplastic Agents, Alkylating / pharmacology*
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Computational Biology
  • Datasets as Topic
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Knockdown Techniques
  • Humans
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • MicroRNAs / agonists
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Prognosis
  • Survival Rate
  • Up-Regulation / drug effects

Substances

  • Antineoplastic Agents, Alkylating
  • MIRN1293 microRNA, human
  • MicroRNAs
  • Alcohol Oxidoreductases
  • HAO2 protein, human