中国肿瘤生物治疗杂志2025，Vol.32Issue(1)：38-47,10.DOI:10.3872/j.issn.1007-385x.2025.01.006
KHSRP靶向调控JAK1/STAT3信号通路对食管胃结合部腺癌恶性生物学行为的影响
Effects of KHSRP targeting JAK1/STAT3 signaling pathway on the malignant biological behavior of the adenocarcinoma of esophagogastric junction
摘要
Abstract
Objective:To investigate the effects of KH-type splicing regulatory protein(KHSRP)targeting and regulating JAK1/STAT3 signaling axis on the proliferation,migration and invasion of the adenocarcinoma of esophagogastric junction(AEG)cells,as well as the growth of transplanted tumors and lung metastasis.Methods:A total of 64 pairs of AEG tissue and adjacent normal tissue samples,along with clinical data from patients diagnosed at Huaihe Hospital from January 2017 to December 2018 were collected.The expression level of KHSRP in AEG tissues and adjacent normal tissues was observed using immunohistochemical staining.The differential expression of KHSRP in AEG cells(OE-19,TE-7,BIC-1,FLO-1,SK-GT-4,BE-3)and normal esophageal epithelial cells(Het-1A)was detected by qPCR.Lentiviral vectors were used to knockdown and overexpress KHSRP in OE-19,TE-7,FLO-1,and SK-GT-4 cells.The experiment was divided into the following groups:sh-NC group,sh-KHSRP group,Vector group,and KHSRP overexpression group(KHSRP group).The knockdown or overexpression efficiency was detected by qPCR,and the effects of KHSRP knockdown or overexpression on AEG cell proliferation,migration and invasion were evaluated using CCK-8 and Transwell assays,respectively.A mouse xenograft and lung metastasis model was established to observe the effects of KHSRP on tumor growth and metastasis in vivo.The targeted regulation of JAK/STAT signaling pathway by KHSRP was verified by Western blotting.A rescue experiment was conducted to verify whether KHSRP promoted malignant progression of AEG cells through the JAK1/STAT3 signaling pathway.Results:Compared with adjacent normal tissues,the expression level of KHSRP in AEG tissues was significantly increased(P<0.05 or P<0.01).Cell function experiments showed that KHSRP overexpression significantly promoted AEG cell proliferation,migration,and invasion in vitro(P<0.05 or P<0.01).In vivo animal experiments showed that KHSRP promoted AEG cell xenograft tumor growth and lung metastasis in nude mice(P<0.05 or P<0.01).After KHSRP knockdown,the phosphorylation levels of JAK1 and STAT3 in the JAK/STAT signaling pathway were significantly reduced,while overexpression of KHSRP led to the opposite results(P<0.05 or P<0.01).Rescue experiment showed that KHSRP could reverse the inhibition of cell proliferation,migration,and invasion caused by JAK1/STAT3 knockdown(P<0.05 or P<0.01).Conclusion:KHSRP regulates the malignant progression of AEG cells by activating JAK1/STAT3 signaling axis.KHSRP may become a potential target for the clinical treatment of AEG.关键词
食管胃结合部腺癌/KHSRP/JAK1/STAT3信号通路/增殖/迁移/侵袭/小鼠模型Key words
adenocarcinoma of esophagogastric junction(AEG)/KH-type splicing regulatory protein(KHSRP)/JAK1/STAT3 signaling pathway/proliferation/migration/invasion/mouse model分类
临床医学引用本文复制引用
张海峰,王梦瑶,王晓龙,刘洋洋,李丽,韦海涛..KHSRP靶向调控JAK1/STAT3信号通路对食管胃结合部腺癌恶性生物学行为的影响[J].中国肿瘤生物治疗杂志,2025,32(1):38-47,10.基金项目
河南省教育厅资助项目(No.24A320002,No.25B320018,No.25B320022) （No.24A320002,No.25B320018,No.25B320022）
河南省科技厅指导项目(No.232102310007,No.242102310184,No.242102310197) （No.232102310007,No.242102310184,No.242102310197）
