Circ-PITX1 promotes non-small-cell lung cancer progression through regulating ETS1 expression via miR-615-5p.

Background: Circular RNAs (circRNAs), produced by reverse splicing, act as important players in human cancers. We aimed to assess the biological functions of circRNA pituitary homeobox 1 (circ-PITX1) in non-small-cell lung cancer (NSCLC).

Methods: qRT-PCR was employed to determine RNA expression. Biological behaviors of NSCLC cells were assessed by CCK-8, colony formation, EdU assay, flow cytometry, wound healing, and transwell assays. Glutamine catabolism was examined via the measurement of glutamine consumption, α-ketoglutarate levels, as well as ATP levels. Protein levels were detected by western blot assays. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to reveal the mechanism responsible for circ-PITX1 regulating NSCLC cell malignancy. The murine xenograft model was established to investigate circ-PITX1's effect on tumor formation.

Results: Circ-PITX1 was overexpressed in NSCLC tissue samples and cells. Its low expression repressed NSCLC cell proliferation and motility. Moreover, our data revealed its downregulation inhibited glutamine catabolism and tumor formation and promoted cell apoptosis. In addition, circ-PITX1 bound to miR-615-5p, and its inhibitory effect on tumor cellular behaviors could be reversed after decreasing miR-615-5p expression. The miRNA targeted E26 transformation specific-1 (ETS1), whose upregulation abolished miR-615-5p overexpression-induced effects in NSCLC cells. Furthermore, circ-PITX1 positively modulated ETS1 production through interaction with miR-615-5p.

Conclusion: Circ-PITX1 facilitated NSCLC progression via modulating miR-615-5p/ETS1 pathway.