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共沉默 HHLA2 和 EGFR 表达对结直肠癌细胞 增殖、迁移和侵袭的影响

作者:时间:2025-07-04点击数:



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文章编号:1672-6987(2025)03-0021-06;DOI:10. 16351/j. 1672-6987. 2025. 03. 003


安仲华 1 ,王一凡 1 ,吴孟冉 1 ,郑浩天 1 ,胡水清 2 ,王宏波 2 ,公衍玲 1

1. 青岛科技大学 化工学院,山东 青岛 266042; 2. 青岛市即墨区人民医院,山东 青岛 266200)

要:探讨共沉默人类内源性逆转录病毒-H长末端重复关联蛋白 2(HHLA2)和表皮生长因子 受体(EGFR)对结直肠癌 RKO 细胞增殖、迁移和侵袭的影响及可能机制。采用小干扰 RNA (siRNA)技术沉默 HHLA2和 EGFR的表达;分别采用 MTT法、划痕实验法、Transwell实验观察 结直肠癌 RKO 细胞的增殖、迁移和侵袭能力;采用 Western blot检测 HHLA2,EGFR,p-EGFR, MEK1/2,p-MEK1/2,ERK1/2 和 p-ERK1/2 蛋 白 的 表 达 。 结 果 发 现 ,分 别 沉 默 HHLA2 和 EGFR的表达均可抑制结直肠癌 RKO细胞的增殖、迁移和侵袭。同时,除了 HHLA2和 EGFR的 表达显著降低外,还出现 p-EGFR、p-MEK1/2 和 p-ERK1/2 的表达显著下降。共沉默 HHLA2 和 EGFR的表达,上述抑制作用明显加强。共沉默 HHLA2和 EGFR的表达能显著抑制结直肠癌 细胞的增殖、迁移和侵袭,这一作用可能与抑制 EGFR 沉默引起的 HHLA2 上调和抑制 MEK/ ERK通路激活有关。实验结果可为解决 EGFR靶向治疗耐药性提供联合用药参考。


关键词:结直肠癌; siRNA; HHLA2; EGFR; MEK/ERK 通路;细胞增殖;细胞侵袭


中图分类号:R 966 文献标志码:A


引用格式:安仲华,王一凡,吴孟冉,等 . 共沉默 HHLA2 和 EGFR 表达对结直肠癌细胞增

殖、迁移和侵袭的影响[J]. 青岛科技大学学报(自然科学版),2025,46(3):21-26.


AN Zhonghua, WANG Yifan, WU Mengran, et al. Effect of co-siliencing of HHLA2 and

EGFR expression on the proliferation, migration, and invasion of colorectal cancer cells[J]. Journal of Qingdao University of Science and Technology(Natural Science Edition),2025,46 (3):21-26.


Effect of Co-Siliencing of HHLA2 and EGFR Expression on the

Proliferation, Migration, and Invasion of Colorectal Cancer Cells


AN Zhonghua1 ,WANG Yifan1 ,WU Mengran1 ,ZHENG Haotian1 ,HU Shuiqing2 ,

WANG Hongbo2 ,GONG Yanling1 (1. College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China; 2. Jimo District People's Hospital, Qingdao 266200, China)


Abstract:To explore the effects and possible mechanisms of the co-siliencing of human endog enous retrovirus-H long terminal repeat-associating 2(HHLA2) and epidermal growth factor receptor (EGFR) expression on the proliferation, migration, and invasion of colorectal cancer RKO cells. Small interfering RNA (siRNA) was employed to silence the expression of HHLA2 and EGFR; MTT, scratch assay and Transwell assay were used to observe the prolif eration, migration and invasion of colorectal cancer RKO cells. EGFR, p-EGFR, MEK, pMEK, ERK1/2 and p-ERK1/2 proteins were measured by Western blot. The results demon strated that siliencing the expression of HHLA2 and EGFR inhibited the proliferation, migration

and invasion of RKO cells, respectively. Meanwhile, the expression of p-EGFR, p-MEK and p-ERK1/2 decreased significantly in addition to HHLA2 and EGFR. Co-silencing the expres sion of HHLA2 and EGFR significantly enhanced the above inhibition effect. Co-silencing the expression of HHLA2 and EGFR can significantly inhibit the proliferation, migration and inva sion of colorectal cancer cells, which may be related to the inhibition of HHLA2 upregulation induced by EGFR silencing as well as the activation of MEK/ERK pathway. The experimental results can provide a reference for solving the drug resistance of EGFR targeted therapy.


Key words:colorectal cancer; siRNA; HHLA2; EGFR; MEK/ERK signaling pathway; cellproliferation; cell invasion



收稿日期:2024-07-12

基金项目:青岛市医药科研指导计划项目(2020);青岛市医疗卫生 C 类重点学科建设项目(2022);山东省大学生创新训练计划项目

S202210426086).

作者简介:安仲华(1997—),男,硕士研究生 . 通信联系人 .



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