MiR-501-3p promotes osteosarcoma cell proliferation, migration and invasion by targeting BCL7A

Hum Cell. 2021 Mar;34(2):624-633. doi: 10.1007/s13577-020-00468-x. Epub 2021 Jan 7.

Abstract

Increasing numbers of evidences have demonstrated that microRNAs (miRNAs) play an important role in osteosarcoma (OS) cell functions. MiR-501-3p has been reported to play an important role in several types of tumors, including prostate cancer and hepatocellular carcinoma. However, the biological function and potential mechanism of miR-501-3p in OS have not been well investigated until now. Here, we analyzed the expression of miR-501-3p in OS tissues and cell lines and its clinical significance in OS patients. Quantitative reverse transcription PCR showed miR-501-3p was significantly up-regulated in OS tissues and cell lines. Up-regulated miR-501-3p expression was associated with TNM stage, distal metastasis and worse prognosis in OS patients. MiR-501-3p knockdown and overexpression were achieved by miR-501-3p inhibitor and mimics transfection, respectively. CCK-8, colony formation and transwell assays showed that miR-501-3p knockdown in U2OS and Saos-2 cells suppressed, while miR-501-3p overexpression in Saos-2 cells promoted cell proliferation, migration and invasion. Moreover, luciferase reporter assay supporting BCL7A was a target of miR-501-3p and its expression was increased by miR-501-3p inhibitor, but inhibited by miR-501-3p mimics. By performing rescue experiments, we further demonstrated that BCL7A was a downstream functional regulator involved in miR-501-3p promoting OS cell functions. In summary, our findings suggest that miR-501-3p targets BCL7A may provide novel therapeutic targets for the treatment of OS.

Keywords: BCL7A; Metastasis; Osteosarcoma; Prognosis; Proliferation; miR-501-3p.

MeSH terms

  • Adult
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Female
  • Gene Expression / genetics*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • MicroRNAs / physiology*
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism*
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Metastasis / genetics*
  • Neoplasm Metastasis / pathology*
  • Neoplasm Staging
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism*
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology*
  • Young Adult

Substances

  • BCL7A protein, human
  • MIRN501 microRNA, human
  • MicroRNAs
  • Microfilament Proteins
  • Oncogene Proteins