南方医科大学学报

南方医科大学学报 ›› 2024, Vol. 44 ›› Issue (9): 1760-1768.doi: 10.12122/j.issn.1673-4254.2024.09.16

• • 上一篇    下一篇

KHSRP高表达促进胃腺癌转移：JAK1/STAT3信号轴的介导作用

张卉1(), 刘洋洋2(), 李霞鹏3, 王梦瑶2, 李丽2,3(), 韦海涛3()   

  1. 1.河南大学淮河医院，消化科，河南 开封 475001
    3.河南大学淮河医院，胸外科，河南 开封 475001
    2.河南大学护理与健康学院慢病研究所，河南 开封 475004
  • 收稿日期:2024-07-04 出版日期:2024-09-20 发布日期:2024-09-30
  • 通讯作者: 李丽,韦海涛 E-mail:3835206455@qq.com;104754222009@henu.edu.cn;10210051@vip.henu.edu.cn;taoge9885@163.com
  • 作者简介:张 卉，副主任医师，硕士，E-mail: 3835206455@qq.com
    刘洋洋，在读硕士研究生，E-mail: 104754222009@henu.edu.cn
    第一联系人：（张 卉、刘洋洋并列第一作者）
  • 基金资助:
    河南省教育厅资助项目(24A320002);河南省科技厅指导项目(242102310100)

High KHSRP expression promotes gastric adenocarcinoma metastasis: the mediating role of the JAK1/STAT3 signaling axis

Hui ZHANG1(), Yangyang LIU2(), Xiapeng LI3, Mengyao WANG2, Li LI2,3(), Haitao WEI3()   

  1. 1.Department of Gastroenterology, Henan University, Kaifeng 475001, China
    3.Department of Thoracic Surgery, Huaihe Hospital, Henan University, Kaifeng 475001, China, Henan University, Kaifeng 475001, China
    2.Institute of Nursing and Health, Henan University, Kaifeng 475001, China
  • Received:2024-07-04 Online:2024-09-20 Published:2024-09-30
  • Contact: Li LI, Haitao WEI E-mail:3835206455@qq.com;104754222009@henu.edu.cn;10210051@vip.henu.edu.cn;taoge9885@163.com

RichHTML

10

PDF

361

摘要：

目的 探究KHSRP通过JAK1/STAT3信号轴调控胃腺癌转移恶性进展及其潜在的分子机制。 方法 采用qRT-PCR检测胃腺癌细胞系（MKN-28、HGC-27、CRL-5822、SNU-1）及人正常胃黏膜细胞系（GES-1）中KHSRP的表达量。CCK-8、Transwell迁移/侵袭实验分别检测细胞增殖、迁移和侵袭等生物学特征。采用Western blotting法检测稳定转染细胞中JAK/STAT、KHSRP蛋白的表达水平。将HGC-27、SNU-1注射至裸鼠体内，对裸鼠进行皮下荷瘤敲降组（5只/组）和过表达组（5只/组）和尾静脉注射模型实验敲降组（5只/组）和过表达组（5只/组），观察STAD细胞在裸鼠体内的生长情况。 结果 qRT-PCR结果显示，与人正常胃腺癌黏膜上皮细胞（GES-1）和组织相比，KHSRP在胃腺癌细胞系（MKN-28、HGC-27、CRL-5822、SNU-1）和肿瘤组织中的表达显著升高（P<0.05）。细胞功能实验显示，与sh-NC组相比，sh-KHSRP组HGC-27细胞抑制细胞增殖、细胞迁移、侵袭，Vector组SNU-1细胞促进细胞增殖、迁移、侵袭（P<0.05）。裸鼠实验中，与sh-NC组相比，sh-KHSRP组裸鼠肿瘤体积和质量、细胞增殖率和胃腺癌转移病灶数目明显减少（P<0.05）；过表达结果相反（P<0.05）。信号通路实验显示，与sh-NC组相比，sh-KHSRP组JAK1、STAT3的表达量显著下调（P<0.05），过表达组结果相反（P<0.05）。 结论 KHSRP可通过JAK1/STAT3信号轴，促进胃腺癌转移的恶性进程。

关键词: 胃腺癌, 分子机制, JAK1, STAT3, KHSRP

Abstract:

Objective To investigate the regulatory effect of KHSRP on progression of gastric adenocarcinoma and the role of the JAK1/STAT3 signaling axis in mediating its effect. Methods KHSRP mRNA expression level was detected using qRT-PCR in 120 pairs of gastric adenocarcinoma and adjacent tissues, 4 gastric adenocarcinoma cell lines (MKN-28, HGC-27, CRL-5822, and SNU-1) and normal human gastric mucosal GES-1 cells. In HGC-27 cells with KHSRP knockdown and SNU-1 cells with KHSRP overexpression, cell proliferation, migration, invasion and expression levels of JAK/STAT were evaluated using CCK-8 assay, Transwell migration and invasion assays, and Western blotting. In BALB/c-nude mice, HGC-27 cells with KHSRP knockdown and SNU-1 cells overexpressing KHSRP were injected either subcutaneous or via the tail vein to observe subcutaneous xenograft growth and lung metastasis of the tumor cells. Results Gastric adenocarcinoma tissues and cell lines all showed significantly increased KHSRP expression as compared with the adjacent tissues and GES-1 cells. In HGC-27 cells, KHSRP knockdown significantly inhibited cell proliferation, migration and invasion, while KHSRP overexpression enhanced the malignant behaviors of SNU-1 cells. In nude mice, inoculation of HGC-27 cells with KHSRP knockdown resulted in smaller tumor volume and weight, slower cell proliferation rate and fewer lung metastatic foci, and KHSRP-overexpressing SNU-1 cells produced the opposite results. KHSRP knockdown in HGC-27 cells significantly down-regulated the expression levels of JAK1 and STAT3, which were obviously increased in KHSRP-overexpressing SNU-1 cells. Conclusion High expressions of KHSRP promote progression and metastasis of gastric adenocarcinoma possibly by regulating the JAK1/STAT3 signaling axis.

Key words: STAD, molecular mechanism, JAK1, STAT3, KHSRP