Regulatory role of KH-type splicing regulatory protein in lung adenocarcinoma:key role of JAK1/STAT3 pathway
10.3969/j.issn.1671-7856.2025.01.001
- VernacularTitle:KHSRP在肺腺癌中的调控作用:JAK1/STAT3通路的关键角色
- Author:
Chaonan MA
1
;
Mengyao WANG
;
Sa ZHANG
;
Li LI
;
Haitao WEI
Author Information
1. 河南大学淮河医院呼吸与危重症医学科,河南 开封 475099
- Publication Type:Journal Article
- Keywords:
lung adenocarcinoma;
KHSRP;
JAK1/STAT3;
malignant progression;
cell proliferation;
invasion and migration
- From:
Chinese Journal of Comparative Medicine
2025;35(1):1-12
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of KH-type splicing regulatory protein(KHSRP)on the malignant biological behavior of lung adenocarcinoma(LUAD)by targeting the Janus kinase 1(JAK1)/signal transducer and activator of transcription 3(STAT3)signaling axis.Methods Clinical data were collected for 64 patients with LUAD,diagnosed at Huaihe Hospital from January 2017 to December 2018.Expression levels of KHSRP were detected in LUAD tissues and adjacent tissues by immunohistochemical staining.KHSRP gene expression was also detected in LUAD cell lines(SPC-A1,H1975,CL1-5,PC-9,Calu-3,H446)and normal human bronchial epithelial cells using quantitative reverse transcription-polymerase chain reaction.KHSRP expression in SPC-A1,H1975,PC-9,and Calu-3 cells was manipulated by lentivirus transfection.The effects of KHSRP on the proliferation,migration,and invasion of LUAD cells were detected by Cell Counting Kit-8 and Transwell assays.The effects of KHSRP overexpression and knockdown were also investigated in a mouse xenograft tumor model,and JAK/STAT signaling pathway proteins were detected by Western blot.Rescue experiments were conducted to verify if KHSRP promoted the malignant progression of LUAD cells by regulating the JAK1/STAT3 signaling pathway.Results KHSRP expression was significantly higher in LUAD tissues compared with adjacent tissues(P＜0.05).Overexpression of KHSRP significantly promoted the proliferation,migration,and invasion of LUAD cells in vitro(P＜0.05).KHSRP also promoted LUAD cell xenograft tumor growth and lung nodule metastasis in nude mice in vivo(P＜0.01).KHSRP knockdown significantly decreased the levels of JAK1,phospho-JAK1,and STAT3 in the JAK/STAT signaling pathway,while the situation was reversed following KHSRP overexpression(P＜0.05).Rescue experiments showed that KHSRP reversed the inhibitory effect of knockdown(P＜0.05).Conclusions KHSRP targets the JAK1/STAT3 signaling pathway and acts as an oncogene in LUAD.
