Circ-XPO1 upregulates XPO1 expression by sponging multiple miRNAs to facilitate osteosarcoma cell progression

Yang Jiang1, Jiye Hou2, Xiaodong Zhang1

  • 1Department of Anatomy, Basic Medicine College, Qiqihar Medical University, Qiqihar 161000, China.

Insights

Circular RNAs (circRNAs) are key in cancer. This study found elevated circ-XPO1 in osteosarcoma (OS) promotes tumor growth and invasion by regulating XPO1, suggesting circ-XPO1 as a potential therapeutic target for OS.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are implicated in carcinogenesis, but their specific roles in osteosarcoma (OS) remain unclear.
  • Understanding circRNA mechanisms is crucial for developing novel therapeutic strategies against OS.

Purpose of the Study:

  • To investigate the function and mechanism of circ-XPO1 in osteosarcoma progression.
  • To explore the potential of circ-XPO1 as a therapeutic target for OS.

Main Methods:

  • CircRNA microarray and qRT-PCR to quantify circ-XPO1 and XPO1 mRNA expression in OS tissues and cells.
  • Kaplan-Meier analysis to assess the correlation between circ-XPO1/XPO1 expression and patient prognosis.
  • Functional assays (growth, invasion, apoptosis) and rescue assays to determine the role of circ-XPO1 and its interaction network.
  • Construction and verification of the circ-XPO1-miRNAs-XPO1 3'-UTR interaction network.

Main Results:

  • Circ-XPO1 and XPO1 mRNA were significantly upregulated in OS tissues and cells compared to normal samples.
  • Elevated circ-XPO1 and XPO1 mRNA expression correlated with poor prognosis in OS patients.
  • Circ-XPO1 and XPO1 promoted OS cell growth and invasion while inhibiting apoptosis.
  • Circ-XPO1 acts as a competing endogenous RNA (ceRNA) by sponging miR-23a-3p, miR-23b-3p, miR-23c, and miR-130a-5p to regulate XPO1 expression.

Conclusions:

  • Circ-XPO1 plays a significant role in promoting osteosarcoma progression by regulating XPO1 expression via a miRNA sponging mechanism.
  • Circ-XPO1 represents a potential novel therapeutic target for osteosarcoma.

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