Circ-PGC increases the expression of FOXR2 by targeting miR-532-3p to promote the development of non-small cell lung cancer

ABSTRACT

This study was to explore the function of circular progastricsin (circ-PGC) in NSCLC. The histological morphology of tumor tissues was observed by hematoxylin and eosin (HE) staining. The expression of circ-PGC, miR-532-3p and forkhead box R2 (FOXR2) mRNA was measured by real-time quantitative polymerase chain reaction (RT-qPCR). The protein level of FOXR2 was checked by western blot. In functional analyses, cell viability, colony formation, cell apoptosis, cell migration and cell invasion were investigated using cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry assay, wound healing assay and transwell assay. Besides, glycolysis metabolism was assessed by the levels of glucose consumption, lactate production and adenosine triphosphate (ATP) production. The predicted relationship between miR-532-3p and circ-PGC and FOXR2 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The results showed that circ-PGC and FOXR2 were upregulated in NSCLC tissues and cells. Circ-PGC knockdown or FOXR2 knockdown inhibited NSCLC cell viability, colony formation, cell migration, invasion and glycolysis metabolism, and FOXR2 overexpression rescued these inhibitory effects caused by circ-PGC knockdown. MiR-532-3p harbored the same binding site with circ-PGC and FOXR2, and circ-PGC positively regulated FOXR2 expression by targeting miR-532-3p. The expression of β-catenin and c-Myc was decreased in cells after circ-PGC knockdown but recovered with miR-532-3p inhibition or FOXR2 overexpression. Circ-PGC downregulation also inhibited tumor growth in vivo. In conclusion, circ-PGC positively regulated FOXR2 expression by competitively binding to miR-532-3p, thereby promoting the development of NSCLC, and the Wnt/β-catenin signaling pathway might be activated by the circ-PGC/miR-532-3p/FOXR2 network.

KEYWORDS:

• Circ-PGC
• FOXR2
• miR-532-3p
• nsclc
• Wnt/β-catenin

Highlights

1. Circ-PGC and FOXR2 are highly expressed in NSCLC tumor tissues and cells.

2. Circ-PGC knockdown or FOXR2 knockdown inhibits NSCLC cell malignant phenotypes.

3. Circ-PGC positively regulates FOXR2 expression by targeting miR-853-3p.

4. Wnt/β-catenin signaling pathway may be involved in the circ-PGC/miR-532-3p/FOXR2 regulatory network.

5. Circ-PGC downregulation inhibits tumor growth in vivo.

Acknowledgments

Not applicable

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics approval and consent to participate

The present study was approved by the ethical review committee of The First College of Clinical Medical Science, China Three Gorges University. Written informed consent was obtained from all enrolled patients.

Consent for publication

Patients agree to participate in this work

Availability of data and materials

The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was not received funding.