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

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.