国际肿瘤学杂志

国际肿瘤学杂志 ›› 2026, Vol. 53 ›› Issue (3): 129-136.doi: 10.3760/cma.j.cn371439-20250530-00021

• 论著 • 上一篇    下一篇

lncRNA CASC19调节miR-410-3p/LAMC1信号通路对乳腺癌细胞增殖、迁移和侵袭的影响

李瑶, 田林, 刘昊麟, 肖婧()   

  1. 湖北省十堰市人民医院（湖北医药学院附属人民医院）病理科，十堰 442000
  • 收稿日期:2025-05-30 出版日期:2026-03-08 发布日期:2026-02-09
  • 通讯作者: 肖婧，Email： 66385261@qq.com

Effects of lncRNA CASC19 on proliferation，migration and invasion of breast cancer cells by regulating miR-410-3p/LAMC1 signaling pathway

Li Yao, Tian Lin, Liu Haolin, Xiao Jing()   

  1. Department of Pathology，Shiyan Renmin Hospital of Hubei Province，Renmin Hospital Affiliated to Hubei University of Medicine，Shiyan 442000，China
  • Received:2025-05-30 Online:2026-03-08 Published:2026-02-09

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摘要：

目的 探讨长非编码RNA（lncRNA）癌易感性候选基因19（CASC19）调节微RNA-410-3p（miR-410-3p）/层粘连蛋白γ1（LAMC1）信号通路对乳腺癌细胞增殖、迁移和侵袭的影响。方法 收集2023年1月至2024年1月湖北省十堰市人民医院治疗的53例乳腺癌患者的乳腺癌组织和癌旁组织。将乳腺癌MCF-7细胞分为NC组、sh-NC组、sh-CASC19组、sh-CASC19+anti-NC组、sh-CASC19+anti-miR-410-3p组。采用双荧光素酶报告基因实验检测CASC19与miR-410-3p、miR-410-3p与LAMC1的互作关系。采用实时荧光定量PCR检测乳腺癌组织和癌旁组织以及各组MCF-7细胞CASC19、miR-410-3p、LAMC1 mRNA的表达情况，采用EdU染色法和CCK-8法检测细胞增殖能力，采用划痕实验检测细胞迁移能力，采用Transwell实验检测细胞侵袭能力，蛋白质印迹法检测增殖细胞核抗原（PCNA）、LAMC1、基质金属蛋白酶-2（MMP-2）蛋白的表达情况。结果 癌旁组织、乳腺癌组织CASC19相对表达量分别为1.01±0.30、1.65±0.31，miR-410-3p分别为0.99±0.17、0.53±0.15，LAMC1分别为1.00±0.29、1.48±0.31，差异均有统计学意义（t=37.92，P<0.001；t=37.87，P<0.001；t=21.24，P<0.001）。双荧光素酶报告基因实验结果显示，CASC19可以靶向负调控miR-410-3p，miR-410-3p可以靶向负调控LAMC1。NC组、sh-NC组、sh-CASC19组、sh-CASC19+anti-NC组、sh-CASC19+anti-miR-410-3p组乳腺癌MCF-7细胞CASC19相对表达量分别为1.01±0.16、0.96±0.16、0.37±0.13、0.34±0.11、0.35±0.11，miR-410-3p分别为1.00±0.33、1.07±0.34、1.92±0.38、1.88±0.39、1.34±0.37，LAMC1 mRNA分别为1.00±0.17、1.05±0.17、0.44±0.13、0.41±0.13、0.89±0.15，差异均有统计学意义（F=39.05，P<0.001；F=8.72，P<0.001；F=25.21，P<0.001）；与NC组、sh-NC组相比，sh-CASC19组、sh-CASC19+anti-NC组、sh-CASC19+anti-miR-410-3p组CASC19表达均显著降低（均P<0.05），sh-CASC19组、sh-CASC19+anti-NC组miR-410-3p表达显著升高，LAMC1 mRNA表达均显著降低（均P<0.05）；与sh-CASC19组、sh-CASC19+anti-NC组相比，sh-CASC19+anti-miR-410-3p组miR-410-3p表达显著降低，LAMC1表达显著升高（均P<0.05）。5组细胞EdU阳性细胞率分别为（45.93±5.04）%、（46.07±5.13）%、（19.26±3.25）%、（20.43±3.36）%、（37.85±4.86）%，细胞活力分别为（100.00±0.00）%、（97.26±9.87）%、（46.27±7.12）%、（47.23±7.08）%、（86.39±9.05）%，差异均有统计学意义（F=54.34，P<0.001；F=76.76，P<0.001）。5组细胞划痕愈合率分别为（47.85±4.90）%、（48.03±4.87）%、（23.97±3.51）%、（23.42±3.26）%、（39.54±4.12）%，侵袭数分别为（114.62±10.98）、（113.78±11.87）、（64.53±9.41）、（65.14±9.04）、（97.86±10.27）个，差异均有统计学意义（F=51.26，P<0.001；F=34.81，P<0.001）。5组细胞PCNA蛋白表达分别为1.14±0.14、1.17±0.15、0.34±0.10、0.36±0.11、0.93±0.13，LAMC1分别为1.37±0.15、1.32±0.14、0.59±0.09、0.61±0.09、1.18±0.12，MMP-2分别为0.93±0.13、0.88±0.10、0.23±0.07、0.25±0.08、0.76±0.10，差异均有统计学意义（F=62.32，P<0.001；F=58.94，P<0.001；F=73.41，P<0.001）。与NC组、sh-NC组相比，sh-CASC19组、sh-CASC19+anti-NC组EdU阳性细胞率、细胞活力、划痕愈合率、侵袭数、PCNA、LAMC1、MMP-2蛋白均显著降低（均P<0.05）；与sh-CASC19组、sh-CASC19+anti-NC组相比，sh-CASC19+anti-miR-410-3p组均显著升高（均P<0.05）。结论 lncRNA CASC19可能通过调节miR-410-3p/LAMC1信号通路促进乳腺癌细胞的增殖、迁移和侵袭能力。

关键词: 乳腺肿瘤, 细胞增殖, 细胞运动, 肿瘤浸润, 微RNA-410-3p, 癌易感性候选基因, 层粘连蛋白γ1

Abstract:

Objective To investigate the effects of long non-coding RNA （lncRNA） cancer susceptibility candidate 19 （CASC19） on the proliferation，migration and invasion of breast cancer cells by regulating the microRNA-410-3p （miR-410-3p）/laminin γ1 （LAMC1） signaling pathway. Methods A total of 53 pairs of breast cancer tissues and adjacent tissues of patients treated at Shiyan Renmin Hospital of Hubei Province from January 2023 to January 2024 were collected. The breast cancer MCF-7 cells were divided into the NC group，the sh-NC group，the sh-CASC19 group，the sh-CASC19+anti-NC group，and the sh-CASC19+anti-miR-410-3p group. The interaction between CASC19 and miR-410-3p，and between miR-410-3p and LAMC1 were verified by dual-luciferase reporter gene assay. The expression levels of CASC19，miR-410-3p and LAMC1 mRNA of MCF-7 cells in breast cancer tissues and adjacent tissues and in each group were detected by quantitative real-time PCR，cell proliferation was measured by EdU staining and CCK-8 assay，cell migration ability was evaluated by scratch assay，cell invasion ability was determined by Transwell assay，Western blotting was applied to detect the expression of proliferating cell nuclear antigen （PCNA），LAMC1，and matrix metalloproteinase-2 （MMP-2） proteins. Results The relative expression levels of CASC19 in adjacent tissues and breast cancer tissues were 1.01±0.30 and 1.65±0.31，respectively，miR-410-3p were 0.99±0.17 and 0.53±0.15，respectively，and LAMC1 were 1.00±0.29 and 1.48±0.31，respectively，with statistically significant differences （t=37.92，P<0.001； t=37.87，P<0.001； t=21.24，P<0.001）. The results of the dual-luciferase reporter gene assay showed that，CASC19 could target and negatively regulate miR-410-3p，and miR-410-3p could target and negatively regulate LAMC1. The relative expression levels of CASC19 in breast cancer MCF-7 cells from the NC，sh-NC，sh-CASC19，sh-CASC19+anti-NC，and sh-CASC19+anti-miR-410-3p groups were 1.01±0.16，0.96±0.16，0.37±0.13，0.34±0.11，0.35±0.11，respectively，miR-410-3p were 1.00±0.33，1.07±0.34，1.92±0.38，1.88±0.39，1.34±0.37，respectively，and LAMC1 mRNA were 1.00±0.17，1.05±0.17，0.44±0.13，0.41±0.13，0.89±0.15，respectively，with statistically significant differences （F=39.05，P<0.001； F=8.72，P<0.001； F=25.21，P<0.001）. Compared with the NC and sh-NC groups，the expression of CASC19 in the sh-CASC19，sh-CASC19+anti-NC，and sh-CASC19+anti-miR-410-3p groups decreased significantly （all P<0.05），the expression of miR-410-3p in sh-CASC19 group and sh-CASC19+anti-NC group increased significantly，while the expression of LAMC1 mRNA decreased significantly （all P<0.05）. Compared with the sh-CASC19 and sh-CASC19+anti-NC groups，the expression of miR-410-3p in the sh-CASC19+anti-miR-410-3p group decreased significantly，while the expression of LAMC1 increased significantly （all P<0.05）. The EdU-positive cell rates in the five groups were （45.93±5.04）%，（46.07±5.13）%，（19.26±3.25）%，（20.43±3.36）%，（37.85±4.86）%，respectively，the cell viability values were （100.00±0.00）%，（97.26±9.87）%，（46.27±7.12）%，（47.23±7.08）%，and （86.39±9.05）%，respectively，with statistically significant differences （F=54.34，P<0.001； F=76.76，P<0.001）. The scratch healing rates were （47.85±4.90）%，（48.03±4.87）%，（23.97±3.51）%，（23.42±3.26）%，and （39.54±4.12）%，respectively，the numbers of invasion were 114.62±10.98，113.78±11.87，64.53±9.41，65.14±9.04，97.86±10.27，respectively，with statistically significant differences （F=51.26，P<0.001； F=34.81，P<0.001）. The protein expression levels of PCNA were 1.14±0.14，1.17±0.15，0.34±0.10，0.36±0.11，0.93±0.13，respectively，LAMC1 were 1.37±0.15，1.32±0.14，0.59±0.09，0.61±0.09，and 1.18±0.12，respectively，MMP-2 were 0.93±0.13，0.88±0.10，0.23±0.07，0.25±0.08，0.76±0.10，respectively，with statistically significant differences （F=62.32，P<0.001； F=58.94，P<0.001； F=73.41，P<0.001）. Compared with the NC and sh-NC groups，the EdU-positive cell rate，cell viability value，scratch healing rate，number of invasion，and protein expression levels of PCNA，LAMC1，and MMP-2 in the sh-CASC19 and sh-CASC19+anti-NC groups decreased significantly （all P<0.05）. Compared with the sh-CASC19 and sh-CASC19+anti-NC groups，these indices in the sh-CASC19+anti-miR-410-3p group increased significantly （all P<0.05）. Conclusions lncRNA CASC19 may promote the proliferation，migration，and invasion of breast cancer cells by regulating the miR-410-3p/LAMC1 signaling pathway.

Key words: Breast neoplasms, Cell proliferation, Cell movement, Neoplasm invasiveness, Micro- RNA-410-3p, Cancer susceptibility candidate gene, Laminin γ1