ObjectiveTo investigate the effect of protein arginine methyltransferase 5 （PRMT5） on the angiogenesis of colorectal cancer （CRC） through the Janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） signaling pathway. MethodsThe expression and prognostic value of PRMT5 in CRC tissues were analyzed based on the cancer genome atlas （TCGA） and gene expression omnibus （GEO） databases. A total of 105 pairs of cancer tissues and matched adjacent non-tumor tissues were collected from CRC patients， and PRMT5 expression was detected by immunohistochemistry （IHC）； Western blot was used to detect the PRMT5 protein level in normal colonic epithelial cells （FHC） and CRC cell lines （including RKO， SW480）. SW48 and LoVo cells were divided into negative control （NC） group and PRMT5 knockdown interference group. After the stable knockdown cell models were successfully constructed， the effects of conditioned medium on the proliferation， cell cycle， migration and tube formation abilities of human umbilical vein endothelial cells （HUVECs） were detected； the correlation between PRMT5 and vascular endothelial growth factor A （VEGFA） was analyzed by real-time quantitative polymerase chain reaction （RT-qPCR） and enzyme-linked immunosorbent assay （ELISA）. Gene set enrichment analysis （GSEA） and cytoplasm-nucleus separation assay were performed to verify the regulatory pathway. ResultsPRMT5 was highly expressed in CRC tissues and cell lines， which was significantly correlated with poor prognosis and pathological characteristics of patients （all P<0.05）； PRMT5 knockdown could significantly inhibit the angiogenesis-related abilities of HUVECs （all P<0.05） and down-regulate the expression of VEGFA （all P<0.01）. GSEA results indicated that PRMT5 expression was significantly associated with the activation of JAK2/STAT3 signaling pathway （all P<0.001）. PRMT5 knockdown could inhibit the activation of JAK2/STAT3， the nuclear translocation of STAT3 and the protein level of phosphorylated STAT3 （p-STAT3） in the nucleus， thus inhibiting the expression of VEGFA. ConclusionPRMT5 is highly expressed in CRC tissues and indicates poor prognosis of patients. It promotes the nuclear translocation and transcriptional activity of STAT3 by activating the JAK2/STAT3 pathway and drives the expression of VEGFA to promote tumor angiogenesis.

purpose To investigate the protective effect and character of dl-praeruptorin A(Pd-Ia)on focal cerebral ischemia in mice.Methods Transient focal cerebral ischemia in mice WaS induced by middle cerebral artery occlusion for 1.5 h.Pd-Ia was administered intraperitoneally either with multiple doses(1,5 and 10ms/ks)at 0.5 h before ischemia or single dose(5 ms/kg)at 0.5 h and 1 h before ischemic,the same time of ischemia,the same time of reperfusion,or 0.5 h and 1 h after reperfusion respectively.Neurological deficit score,infarct volume,brain edema,the activities of SOD and the contents of MDA were determined.Results Pretreatment with multiple doses(5 and 10 ms/ks)of Pd-Ia at 0.5 h before ischemia or single dose(5 mg/kg)of Pd-Ia at 0.5 h before ischemia,at the same time of ischemic,at the same time of reperfusion and 0.5 h after reperfusion significantly attenuated neurological deficit score,decreased infarct volume and alleviated brain edema,and the treatment at the time of reperfusion had the most marked effect.Pd-Ia(5 or 10 ms/ks)can significantly enhance the activities of SOD and lower the contents MDA.Conclusion dl-praeruptorin A has a neuroprotective effect on the injury in the acute phase of transient focal cerebral ischemia in mice,with optimal doses of 5 ms/ks and the optimal therapeutic time point of the same time of reperfusion.