Molecular Mechanism of KHSRP/JAK1/STAT3 Signaling Axis High Expression to Promote Metastasis of Cardia Gastric Cancer
10.3870/j.issn.1672-0741.24.07.034
- VernacularTitle:KHSRP/JAK1/STAT3信号轴高表达促进贲门胃癌转移的分子机制研究
- Author:
Feng ZHANG
1
;
Yangyang LIU
;
Xiapeng LI
Author Information
1. 河南大学淮河医院胸外科,开封 475001
- Publication Type:Journal Article
- Keywords:
JAK1;
STAT3;
KHSRP;
cardia gastric cancer;
molecular mechanism
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2025;54(3):343-351
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate how KHSRP regulates the malignant development process of cardia gastric cancer through JAK1/STAT3 signaling pathway,and to reveal the molecular mechanisms.Methods Quantitative real-time fluores-cence polymerase chain reaction(qRT-PCR)was used to detect KHSRP in cancer cell lines(MKN-28,OE-33,HGC-27,KYSE-50,CRL-5822,SNU-1)as well as human normal epithelial cell lines(GES-1).Cell counting kit-8(CCK-8)and Transwell assay were used to detect the biological characteristics of cell proliferation,migration and invasion,respectively.Experimental subjects were divided into four groups in cellular and animal experiments:Sh-KHSRP group(KHSRP knockdown group),Sh-NC group(KHSRP control group),KHSRP group(KHSRP overexpression group),Vector group(KHSRP control group).The expres-sion levels of JAK/STAT and KHSRP proteins in stably transfected cells were detected by Western blotting.The mRNA and protein expression levels of KHSRP in different experimental groups were determined by real-time fluorescence quantitative PCR.Nude mouse experiments were performed to analyze the role of KHSRP in living animals.Results The qRT-PCR showed that the expression of KHSRP was significantly elevated in cancer cell lines(MKN-28,OE-33,HGC-27,KYSE-50,CRL-5822,SNU-1)and tumor tissues compared with human normal epithelial cells(GES-1)and tissues.The results of cell function experi-ments showed that knockdown of OE-33 and HGC-27 cell lines(sh-KHSRP group)significantly inhibited cell proliferation,mi-gration,and invasive ability,whereas the control group(sh-NC group)did not exhibit this inhibitory effect.These features were significantly enhanced in KHSRP overexpressing cells.In nude mice experiments,knockdown of KHSRP in nude mice led to re-duction in tumor volume and weight,lower cell proliferation rate,and lower number of lung nodal metastases compared with the control group(sh-NC group).These changes were reversed while KHSRP was overexpressed.Signaling pathway experiments showed that the expression of JAK1 and STAT3 was significantly downregulated in the sh-KHSRP group compared to the sh-NC group,with opposite results in the overexpression group.The results of cell rescue assay indicated that KHSRP promoted the proliferation,migration and invasion ability of cardia gastric cancer cells by regulating the JAK1/STAT3 signaling path-way.Conclusion KHSRP promotes the malignant process of cardia gastric cancer metastasis by regulating the JAK1/STAT3 signaling axis.
