Fig. 7

CircNSUN2 promotes LM metastasis of CRC through HMGA2 pathway. a, b Decreased tumor metastasis formed in the livers of mice through the inferior hemispleen implantation of circNSUN2-konckdown TC71 PDX cells was rescued by overexpression of HMGA2. a Left, representative bioluminescent images of livers for each experimental group at 8 weeks. Right, statistical analysis of bioluminescent tracking plots. The P values were determined by a two-tailed unpaired Student’s t test. b Left, representative liver. Right, the number of metastatic nodules formed in the livers of mice for each group (n = 6 mice/group). The P values were determined by a two-tailed unpaired Student’s t test. c−e Transwell assay (c), inverted invasion assay (d) and 3D multicellular tumor spheroids invasion assay (e) showing that decreased cell invasion in circNSUN2 knockdown HCT116 cells was rescued by overexpression of HMGA2. Scale bar, 100 µm (c), 100 µm (d) and 10 µm (e). Data represent mean ± S.D. from five independent experiments; dot plot reflects data points from independent experiment. The P values were determined by a two-tailed unpaired Student’s t test. f Left, circNSUN2 expression showing positively correlated with HMGA2 expression in CRC patients derived from SYSUCC. Right, circNSUN2 expression showing positively correlated with CXCR4 expression in CRC patients derived from SYSUCC. The P values were determined by Pearson correlation analysis. g qRT–PCR analysis for the RNA expression of HMGA2 and CXCR4 in 20 pairs of primary colorectal cancer (PC) and matched liver metastasis (LM) surgically obtained from the same patients. Data represent mean ± S.D., the P values were determined by a two-tailed paired Student’s t test. h A proposed model for the regulatory landscape of the circNSUN2/IGF2BP2/HMGA2 signaling axis in promoting the metastasis of CRC. Source data are provided as a Source Data file