Fig 2: HMGA2 facilitates the expressions of FOXM1 and PLAUA. Gene Ontology (GO) analyses of commonly down-regulated genes in TPC1115 GICs depleted with HMGA2, HMGA1 and HMGA2/HMGA1. B. List of GO terms summarizing down-regulated genes in TPC1115 GICs depleted with HMGA2. C. Cell cycle changes of TPC1115 GICs upon knockdown of HMGA2. D. Box plots showing normalized expressions of FOXM1 and PLAU metagene in HMGA2Low and HMGA2High GBMs using data retrieved from TCGA. P values were determined using a nonparametric Wilcoxon test. HMGA2low (n = 471) and HMGA2high (n = 87) expression groups were defined using the minimum P-value approach (maximal chi square statistics approach). E-F. Left: expression levels of FOXM1 (E) and PLAU (F) in 10 normal brains and 557 GBM samples using data retrieved from TCGA; right: Kaplan-Meier survival plots showing correlations of glioma patients' survival with expression levels of FOXM1 (E) and PLAU (F) using the CGGA (Chinese Glioma Genome Atlas) dataset. G. Dual-luciferase assays showing relative luciferase activities of FOXM1 and PLAU promoter fragments (PrFOXM1 and PrPLAU) in U87MG and 293T cells transfected with indicated vectors. O/E, overexpression; H1, HMGA1; H2, HMGA2.

Fig 3: The recovery of HMGA2 expression in GC cells partially reversed the pro‐cancer effect of circ_0000267. (a) Overexpression of circ_0000267 increased HMGA2 expression in MGC‐803 cells, whereas knockdown of circ_0000267 reduced HMGA2 expression in SGC‐7901 cells. (b) HMGA2 in MGC‐803 cells over‐expressing circ_0000267 were knocked down with shRNA, and SGGA‐7901 cells with circ_0000267 knocked down were transfected with HMGA2 overexpression plasmid, and HMGA2 was detected by western blot. (c–i) Overexpression of HMGA2 reversed the inhibition of proliferation, migration, invasion, and EMT processes of SGC‐7901 cells induced by knockdown of circ_0000267, and HMGA2 knockdown reversed the promotion of malignant phenotypes in MGC‐803 cells due to overexpression of circ_0000267. *p < .05, **p < .01, ***p < .001

Fig 4: HMGA2 regulates the proliferation and apoptosis of acute myelocytic leukemia HL60 and NB4 cells. (A) The effect of silencing HMGA2 on cell viability was evaluated by MTT assay in HL60 cells at 24, 48 and 72 h. (B) The effect of overexpressing HMGA2 on cell viability was determined by MTT assay in NB4 cells at 24, 48 and 72 h. (C and D) The effect of HMGA2 on cell apoptosis was determined by flow cytometry in HL60 and NB4 cell. (E) The effects of HMGA2 on the mRNA expressions of XIAP, Bcl-2 and Bax were determined by reverse transcription-quantitative PCR in HL60 and NB4 cells. (F and G) The effects of HMGA2 on the protein expressions of XIAP, Bcl-2, Bax and cleaved caspase-3 were determined by western blotting in HL60 and NB4 cells. GAPDH was used as an internal control. Data were presented as the mean ± standard deviation from three independent experiments. **P<0.05 vs. HL60 cell control; ^P<0.05 and ^^P<0.01 vs. NB4 cell control. HMGA2, high-mobility group AT-hook 2 overexpression group; si-, small interfering RNA; NC, negative control; XIAP, X-linked inhibitor of apoptosis.

Fig 5: HMGA2 inhibited cell apoptosis and increased proliferation(A) Representative cell apoptosis images of S12, SiHa, and CaSki cells 48 hours after transfection with HMGA2 overexpression plasmid or siRNAs were obtained using flow-cytometry. (B) Representative cell clone formation images of S12, SiHa, and CaSki cells 2 weeks after transfection with HMGA2 overexpression plasmid or siRNAs.