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Background: The progression of non-small cell lung cancer (NSCLC) is significantly influenced by circular RNAs (circRNAs), especially in tumor hypoxia microenvironment. However, the precise functions and underlying mechanisms of dysregulated circRNAs in NSCLC remain largely unexplored. Methods: Differentially expressed circRNAs in NSCLC tissues were identified through high-throughput RNA sequencing. The characteristics of circ_0007386 were rigorously confirmed via Sanger sequencing, RNase R treatment and actinomycin D treatment. The effects of circ_0007386 on proliferation and apoptosis were investigated using CCK8, cloning formation assays, TUNEL staining, and flow cytometry assays in vitro. In vivo, xenograft tumor models were used to evaluate its impact on proliferation. Mechanistically, the regulatory relationships of circ_0007386, miR-383-5p and CIRBP were examined through dual luciferase reporter assays and rescue experiments. Additionally, we detected the binding of EIF4A3 to CRIM1 pre-mRNA by RNA immunoprecipitation and the interaction between YAP1 and EIF4A3 under hypoxic conditions by co-immunoprecipitation. Results: Our investigation revealed a novel circRNA, designated as circ_0007386, that was upregulated in NSCLC tissues and cell lines. Circ_0007386 modulated proliferation and apoptosis in NSCLC both in vitro and in vivo. Functionally, circ_0007386 acted as a sponge for miR-383-5p, targeting CIRBP, which influenced NSCLC cell proliferation and apoptosis via the PI3K/AKT signaling pathway. Furthermore, under hypoxic conditions, the interaction between YAP1 and EIF4A3 was enhanced, leading to the displacement of EIF4A4 from binding to CRIM1 pre-mRNA. This facilitated the back-splicing of CRIM1 pre-mRNA, increasing the formation of circ_0007386. The circ_0007386/miR-383-5p/CIRBP axis was significantly associated with the clinical features and prognosis of NSCLC patients. Conclusions: Circ_0007386, regulated by YAP1-EIF4A3 interaction under hypoxia conditions, plays an oncogenic role in NSCLC progression via the miR-383-5p/CIRBP axis. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) play an important role in the progression of non-small cell lung cancer (NSCLC), especially under tumor hypoxia. However, the precise functions and underlying mechanisms of dysregulated circRNAs in NSCLC are largely unknown. Methods: High-throughput RNA sequencing was performed to identify significantly expressed circRNAs in NSCLC tissues. The functions of circ-0001875 in NSCLC cells were investigated in vitro and in vivo. The regulatory relationships of circ-0001875, miR-31-5p and SP1 were examined by dual luciferase reporter assays and rescue experiments. The signal pathway of epithelial-to-mesenchymal transition and the formation of filopodia were analyzed by western blot and immunofluorescence staining. The binding of SP1 to Alu elements was evaluated by RNA immunoprecipitation, and the HIF1α and SP1 interaction was detected by co-immunoprecipitation. Results: We identified the novel Has_circ_0001875 as a significantly upregulated circRNA in NSCLC tissues and cell lines. circ-0001875 promoted the proliferation and metastasis of NSCLC both in vitro and in vivo, and induced NSCLC cells to extend filopodia. Mechanistically, circ-0001875 sponged miR-31-5p to regulate SP1, influencing epithelial-to-mesenchymal transition via the TGFβ/Smad2 signal pathway. SP1 negatively regulated circ-0001875 formation through an AluSq-dependent feedback loop, which was disrupted by competitive binding of HIF1α to SP1 under hypoxia condition. The circ-0001875/miR-31-5p/SP1 axis was associated with the clinical features and prognosis of NSCLC patients. Conclusions: Our results revealed that the circ-0001875/miR-31-5p/SP1 axis and the complex regulatory loops influence NSCLC progression. These findings provide new insights into the regulation of circRNA formation under tumor hypoxia. [ABSTRACT FROM AUTHOR]