Circ100284 promotes invasion and migration of osteosarcoma cells by down-regulating PTEN and EMP1

Eur Rev Med Pharmacol Sci. 2020 Jun;24(12):6540-6550. doi: 10.26355/eurrev_202006_21638.

Abstract

Objective: To investigate the role of circ100284 in osteosarcoma (OS) and the underlying mechanism.

Patients and methods: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the level of circ100284 in OS tissues and cells, and to examine the association between its level and clinicopathological features such as tumor size, tumor stage, and survival time. In addition, circ100284 was knocked out in MG63 and U2OS cells to observe the effect of circ100284 on cell viability, migration, cycle, and apoptosis by Cell Counting Kit-8 (CCK-8), transwell assay, and flow cytometry assay. Correlations of circ100284 with lysine-specific histone demethylase 1A (LSD1) and enhancer of zeste homolog 2 (EZH2) target proteins were analyzed by RNA co-precipitation experiments. Furthermore, the chromatin immunoprecipitation assay (ChIP)-qPCR assay was performed to analyze the relationship between circ100284 and its target protein and target gene.

Results: Circ100284 had a high level in OS tissues. The high expression of circ100284 was positively correlated with tumor size, pathological stage, and lung metastasis, and negatively correlated with patient survival time. Knocking down circ100284 in OS cells damaged the cell viability and invasiveness, blocked cell cycle, and promoted cell apoptosis. Further experiments showed that circ100284 could epigenetically inhibit cell proliferation by negatively regulating Phosphatase and tensin homolog (PTEN) and epithelial membrane protein 1 (EMP1) in OS.

Conclusions: Circ100284 promotes the progression of OS cells by downregulating PTEN and EMP1.

MeSH terms

  • Adult
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Down-Regulation / physiology
  • Female
  • Humans
  • Male
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology
  • PTEN Phosphohydrolase / antagonists & inhibitors
  • PTEN Phosphohydrolase / biosynthesis*
  • PTEN Phosphohydrolase / genetics
  • RNA, Circular / biosynthesis*
  • RNA, Circular / genetics
  • Receptors, Cell Surface / antagonists & inhibitors
  • Receptors, Cell Surface / biosynthesis*
  • Receptors, Cell Surface / genetics
  • Young Adult

Substances

  • Neoplasm Proteins
  • RNA, Circular
  • Receptors, Cell Surface
  • epithelial membrane protein-1
  • PTEN Phosphohydrolase
  • PTEN protein, human