基础医学与临床 ›› 2025, Vol. 45 ›› Issue (9): 1208-1214.doi: 10.16352/j.issn.1001-6325.2025.09.1208

• 研究论文 • 上一篇    下一篇

CircAPLP2通过调节miR-455-3p/STMN1轴抑制人结直肠癌细胞系增殖、迁移和侵袭

韦新闻1, 温小军1, 樊钊强1, 劳锡峰1, 张鲁青1, 钟鸣2*   

  1. 1.宁波市杭州湾医院 普外科,浙江 宁波 315336;
    2.上海交通大学医学院附属仁济医院 胃肠外科,上海 200127
  • 收稿日期:2024-08-08 修回日期:2024-12-01 发布日期:2025-08-27
  • 通讯作者: *drzhongming1966@163.com
  • 基金资助:
    宁波市科技计划项目(202003N4068)

CircAPLP2 inhibits proliferation, migration and invasion of human colorectal cancer cell lines through regulating miR-455-3p/STMN1 axis

WEI Xinwen1, WEN Xiaojun1, FAN Zhaoqiang1, LAO Xifeng1, ZHANG Luqing1, ZHONG Ming2*   

  1. 1. Department of General Surgery, Ningbo Hangzhou Bay Hospital, Ningbo 315336;
    2. Department of Gastrointestinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
  • Received:2024-08-08 Revised:2024-12-01 Published:2025-08-27
  • Contact: *drzhongming1966@163.com

摘要: 目的 探讨环状RNA APLP2(circAPLP2)调节微小RNA-455-3p(miR-455-3p)/Stathmin1(STMN1)轴对人结直肠癌(CRC)细胞系增殖、迁移和侵袭的影响。方法 运用RT-qPCR检测circAPLP2、miR-455-3p和STMN1在CRC细胞系及正常结直肠细胞系中的表达,筛选最佳细胞系;通过MTT法、划痕实验和Transwell小室法分别测定细胞增殖、迁移和侵袭;Western blot测定蛋白表达;双荧光素酶报告基因实验证实miR-455-3p与circAPLP2、STMN1的关系。结果 CircAPLP2在CRC细胞中高表达,miR-455-3p低表达,STMN1高表达;敲低circAPLP2,SW620细胞存活率、划痕愈合率和侵袭数量均下降,同时miR-455-3p水平上调,STMN1、cyclin D1、N-cadherin蛋白表达水平均下调,E-cadherin蛋白表达水平上调(P<0.05);抑制miR-455-3p水平可降低敲低circAPLP2对SW620细胞增殖、迁移和侵袭的抑制作用,同时STMN1、cyclin D1、N-cadherin蛋白表达水平均上调,E-cadherin蛋白表达水平下调(P<0.05);双荧光素酶报告基因实验结果显示circAPLP2靶向负调控miR-455-3p水平,miR-455-3p靶向负调控STMN1表达;裸鼠移植瘤实验发现,敲低circAPLP2影响移植瘤的生长,同时miR-455-3p水平上调,STMN1表达下调(P<0.05)。结论 CircAPLP2通过调控miR-455-3p/STMN1轴抑制结直肠癌细胞系增殖、迁移和侵袭。

关键词: 环状RNA APLP2, miR-455-3p, Stathmin1(STMN1), 结直肠癌, 增殖

Abstract: Objective To investigate the effects of circular RNA APLP2 (circAPLP2) on the proliferation, migration, and invasion of human colorectal cancer (CRC) cell lines by regulating microRNA-455-3p (miR-455-3p)/Stathmin1 (STMN1) axis. Methods RT-qPCR was used to detect the expression of circAPLP2, miR-455-3p and STMN1 in CRC and normal colorectal cell lines and the optimal cell line was screened. Proliferation, migration and invasion were detected by MTT assay, scratch assay and Transwell assay, respectively. The relationship between circAPLP2 and miR-455-3p, between miR-455-3pand STMN1 was confirmed by dual Lucifer's reporter gene assay. Results CircAPLP2 and STMN1 were highly expressed in CRC cells, miR-455-3p showed a low expression. Knocking down circAPLP2 resulted in a decrease in rate of survival and of scratch healing rate and invasion of SW620 cells, An up regulation of miR-455-3p expression, a down regulation of STMN1, cyclin D1, N-cadherin protein expression and an up regulation of E-cadherin protein expression were also found (P<0.05). Inhibition of miR-455-3p expression reversed inhibitory effect of knocking down circAPLP2 on SW620 cell proliferation, migration, and invasion, up-regulated the STMN1, cyclin D1 and N-cadherin protein expression, and down-regulation of E-cadherin protein expression (P<0.05). Dual luciferase reporter gene assay showed that circAPLP2 targeted at negative regulation of miR-455-3p expression, while miR-455-3p targeted at negative regulation of STMN1 expression. Nude mouse transplantation experiment found that knocking down circAPLP2 affected the growth of transplanted tumors, while miR-455-3p expression was up-regulated and STMN1 expression was down-regulated(P<0.05). Conclusions CircAPLP2 inhibits the proliferation, migration and invasion of colorectal cancer cell lines by regulating the miR-455-3p/STMN1 axis.

Key words: circular RNA APLP2, miR-455-3p, Stathmin1 (STMN1), colorectal cancer, proliferation

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