南方医科大学学报

南方医科大学学报 ›› 2024, Vol. 44 ›› Issue (3): 541-552.doi: 10.12122/j.issn.1673-4254.2024.03.16

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高表达LINC00626通过JAK1/STAT3/KHSRP信号轴促进食管胃结合部腺癌转移的恶性进展

张 锋，范林林，康 霞，韦海涛，李 丽   

  1. 河南大学淮河医院胸外科，护理与健康学院，河南 开封 475001
  • 出版日期:2024-03-20 发布日期:2024-04-03

High LINC00626 expression promotes esophagogastric junction adenocarcinoma metastasis: the mediating role of the JAK1/STAT3/KHSRP axis

ZHANG Feng, FAN Linlin, KANG Xia, WEI Haitao, LI Li   

  1. Department of Thoracic Surgery, Huaihe Hospital, Institute of Nursing and Health, Henan University, Kaifeng 475001, China
  • Online:2024-03-20 Published:2024-04-03

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摘要： 目的 探究LINC00626 通过JAK1/STAT3/KHSRP信号轴调控食管胃结合部腺癌的恶性进展及分子机制。方法 收集并比较食管胃结合部腺癌组织和癌旁组织LINC00626、KHSRP的表达水平。qRT- PCR法检测食管腺癌细胞系（OE-19、TE-7、BIC-1、FLO-1、SK-GT-4、BE-3）与正常食管上皮细胞系（Het-1A）中LINC00626、KHSRP的表达差异。利用慢病毒试剂，构建稳定敲降LINC00626的OE-19、TE-7细胞和稳定过表达LINC00626的FLO-1、SK-GT-4。取对数生长期OE-19细胞分为sh-NC组（转染LV3-NC慢病毒）、sh-LINC00626组（转染敲降LINC0062慢病毒），TE-7细胞同上分组；取对数生长期FLO-1细胞分为Vector组（转染LV6-NC慢病毒）、INC00626组（转染过表达LINC0062慢病毒），SK-GT-4细胞同上分组。细胞计数试剂盒-8（CCK-8）、Transwell迁移/侵袭实验检测敲降和过表达LINC00626后对食管腺癌细胞增殖、迁移、侵袭能力。裸鼠皮下成瘤实验、肺转移实验检测敲降和过表达LINC006266在活体动物体内的作用。Western blot实验检测敲降和过表达LINC00626后KHSRP和JAK/STAT通路蛋白的表达情况。结果 LINC00626和KHSRP在食管胃结合部腺癌组织和食管腺癌细胞中表达量显著升高（P<0.05）。敲降LINC00626后，体内和体外食管腺癌细胞的增殖、迁移和侵袭水平显著下降（P<0.01），过表达LINC00626后则效果反之（P<0.01）。在敲降LINC0626后，JAK/STAT信号通路中JAK1、STAT3磷酸化水平明显降低（P<0.05），过表达LINC00626后情况则反之（P<0.05）。结论 LINC00626通过 JAK1/STAT3/KHSRP 信号轴调控食管胃结合部腺癌转移的恶性进程。

关键词: 食管胃结合部腺癌；LINC00626；JAK1/STAT3；KHSRP；转移

Abstract: Objective To investigate the role of JAK1/STAT3/KHSRP axis in mediating the regulatory effect of LINC00626 on progression of esophagogastric junction adenocarcinoma. Methods We collected surgical tumor and adjacent tissue specimens from 64 patients with esophagogastric junction adenocarcinoma and examined the expression levels of LINC00626 and KHSRP. qRT-PCR was used to detect the expressions of LINC00626 and KHSRP in 6 esophageal adenocarcinoma cell lines (OE-19, TE-7, Bic-1, Flo-1, SK-GT-4, and BE-3) and a normal esophageal epithelial cell line (HET-1A). OE-19 and TE-7 cell lines with stable LINC00626 knockdown and FLO-1 and SK-GT-4 cells stably overexpressing LINC00626 were constructed by lentiviral transfection, and the changes in proliferation, migration and invasion of the cells were evaluated using Cell Counting Kit-8 (CCK- 8) assay and Transwell migration/invasion assay. The expressions of KHSRP and JAK/STAT pathway proteins in the transfected cells were detected with Western blotting. The effects of LINC006266 knockdown and overexpression on subcutaneous tumor formation and lung metastasis of OE-19 and FLO-1 cell xenografts were tested in nude mice. Results The expression levels of LINC00626 and KHSRP were significantly increased in esophagogastric junction adenocarcinoma tissues and in esophageal adenocarcinoma cells. LINC00626 knockdown obviously inhibited the proliferation, migration and invasion of esophageal adenocarcinoma cells in vitro and decreased their tumor formation and lung metastasis abilities in nude mice, while overexpression of LINC00626 produced the opposite effects. In esophageal adenocarcinoma cells, LINC0626 knockdown significantly decreased and LINC00626 overexpression strongly enhanced the phosphorylation of JAK1 and STAT3. Conclusion High LINC00626 expression promotes esophageal-gastric junction adenocarcinoma metastasis by activating the JAK1/STAT3/KHSRP signal axis.

Key words: esophagogastric junction adenocarcinoma; LINC00626; JAK1/STAT3; KHSRP; metastasis