PRMT5 promotes angiogenesis in colorectal cancer via the JAK2/STAT3 signaling pathway
10.19405/j.cnki.issn1000–1492.2026.05 002
- VernacularTitle:PRMT5 激活JAK2/STAT3信号通路促进结直肠癌血管生成
- Author:
Wen ZHANG
1
;
Yongyong GENG
2
;
Xijiang TU
3
;
Qianhui YAO
1
;
Wenlong GUO
1
;
Bogang YAO
1
;
Xuling SUN
1
Author Information
1. Department of Gastrointestinal Surgery， The First Affiliated Hospital of Shihezi University， Shihezi 832008
2. Department of General Surgery， General Hospital of Tumxuk City， Third Division， Xinjiang Production and Construction Corps， Tumxuk 844000
3. Department of General Surgery， The 9th Division Hospital of Xinjiang Production and Construction Corps， Baiyang 831399
- Publication Type:Journal Article
- Keywords:
colorectal cancer;
PRMT5;
VEGFA;
JAK2/STAT3 signaling pathway;
angiogenesis;
tumor prognosis
- From:
Acta Universitatis Medicinalis Anhui
2026;61(5):803-811
- CountryChina
- Language:Chinese
-
Abstract:
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.
