Fig 2: Diagrammatic sketch of the working hypothesis. Foxm1 promotes the TGF‐β1‐induced EndMT process in ECs through Smad2/3 signaling pathway and direct binding to and inducing the transcriptional activity of the Snail gene: an EndMT‐promoting transcription factor. ECs: endothelial cells; EndMT: endothelial‐mesenchymal transition; Foxm1: forkhead box M1; Sio A: Siomycin A; TGF‐β, transforming growth factor beta; TGF‐βR: transforming growth factor beta receptor; TSS: transcriptional start site

Fig 3: Circ-0039411 affected proliferation, migration, and EMT relying on FOXM1 in LUAD.a The qRT-PCR and western blot assays was utilized to detect the effect of circ-0039411 inhibition on FOXM1 expression. GAPDH was the internal control. b, c Cell proliferation was detected by EdU (scale bar = 100 μm) and colony formation assays. d Transwell assay was utilized to test the cell migration (scale bar = 100 μm). e Western blot assay was adopted to detect EMT-related proteins. GAPDH was the internal control. **P < 0.01. n.s. meant no significance.

Fig 4: Graphical description of the FOXM1/circ-0039411/IGF2BP3/FOXM1 loop in LUAD cells.FOXM1 promotes the nuclear translocation of β-catenin as well as the transcription of a circRNA (circ-0039411) originated from MMP2, a downstream target of Wnt pathway. Circ-0039411 upregulation facilitates LUAD cell proliferation, migration and EMT. Besides, circ-0039411 enhances the stability of FOXM1 mRNA via recruiting IGF2BP3, thus forming a positive feedback loop.

Fig 5: CASC8 induces EMT via FOXM1, and FOXM1 expression is associated with poor prognosis in non-small cell lung cancer. A. Changes in expression levels FOXM1, E-cadherin, Snail, and cyclin B1 after CASC8 knockdown in A549 cells. Left panel, quantification, *P < 0.05, **P < 0.01. B. As in (A) for H460 cells; C. as in (A) for H1975 cells. D. The FOXM1 levels decreased after CASC8 silencing. E. 31 pairs of clinical tissue samples were collected and qPCR was performed. The expression of CASC8 was higher than in NSCLC tissues in adjacent tissues, P < 0.0001. F. Western blot analysis was performed using the same tissue as in (Fig. 3E).The expression of FOXM1 was higher than in NSCLC tissues in adjacent normal tissues. Bottom panel, quantification, *P < 0.05, **P < 0.01. G. Derived from the GEPIA database, indicating that there is a positive correlation between CASC8 and FOXM1 at the gene level and has statistical significance (P = 0, R = 0.25). H. Derived from GEPIA database, high expression of CASC8 is associated with poor patient prognosis in lung adenocarcinoma (P=0.0028). I. High expression of FOXM1 is associated with poor prognosis of NSCLC, P < 0.0001. Abbreviations: CASC8: cancer susceptibility candidate 8; EMT: epithelial-to-mesenchymal transition; FOXM1: Forkhead box M1, NSCLC: non-small cell lung cancer; qPCR: quantitative real-time polymerase chain reaction.