临床外科杂志 ›› 2025, Vol. 33 ›› Issue (2): 179-182.doi: 10.3969/j.issn.1005-6483.20240237

• 论著 • 上一篇    下一篇

LncRNA FGD5-AS1调节miR-299-5p/KDM4B轴对大肠癌细胞增殖、迁移和侵袭的影响

  

  1. 438000  长江大学附属黄冈市中心医院肿瘤内科(李莹莹)，胃肠外科(杜恒、王飞、曹钰、吴安定、余洁)
  • 收稿日期:2024-02-22 接受日期:2024-02-22 出版日期:2025-02-20 发布日期:2025-02-20
  • 通讯作者: 余洁，Email:yujie1987y@163.com
  • 基金资助:
    湖北省卫生健康委员会卫生健康科研立项面上项目(WJ2021M083)

Impacts of LncRNA FGD5-AS1 on proliferation,migration,and invasion of colorectal cancer cells by regulating the miR-299-5p/KDM4B axis

  1. Department of Medical Oncology,Huanggang Central Hospital Affiliated to Yangtze University,Hubei Huanggang 438000,China
  • Received:2024-02-22 Accepted:2024-02-22 Online:2025-02-20 Published:2025-02-20

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摘要： 目的  探讨长链非编码RNA(LncRNA)含有5个PH结构域的反义RNA1(FGD5-AS1)调节微小RNA-299-5p(miR-299-5p)/组蛋白赖氨酸残基去甲基化酶4B(KDM4B)轴对大肠癌(CRC)细胞增殖、迁移和侵袭的影响。方法 qRT-PCR检测34例CRC病人术中切除的CRC组织和癌旁组织中LncRNA FGD5-AS1、miR-299-5p、KDM4B的表达；将CRC细胞HCT116分为si-NC组、si-FGD5-AS1组、si-FGD5-AS1+inhibitor-NC组、si-FGD5-AS1+miR-299-5p inhibitor组，检测各组中mRNA的水平；分别采用CCK8、划痕实验、Transwell实验检测各组HCT116细胞的增殖、迁移、侵袭；Western blot检测蛋白表达；双荧光素酶报告基因实验验证LncRNA FGD5-AS1与miR-299-5p、miR-299-5p与KDM4B之间的作用机制。结果 CRC组织中LncRNA FGD5-AS1、KDM4B高表达，miR-299-5p低表达(P<0.05)。si-FGD5-AS1组LncRNA FGD5-AS1 mRNA、KDM4B mRNA、OD450、划痕愈合率、侵袭数、PCNA、MMP-2、MMP-9、KDM4B表达低于si-NC组，miR-299-5p mRNA表达高于si-NC组(P<0.05)；与si-FGD5-AS1组、si-FGD5-AS1+inhibitor-NC组相比，si-FGD5-AS1+miR-299-5p inhibitor组miR-299-5p表达降低(P<0.05)，KDM4B mRNA、OD450、划痕愈合率、侵袭数、PCNA、MMP-2、MMP-9、KDM4B表达升高(P<0.05)。LncRNA FGD5-AS1靶向负调控miR-299-5p，miR-299-5p靶向负调控KDM4B。结论 敲低LncRNA FGD5-AS1可能通过调节miR-299-5p/KDM4B信号轴，抑制CRC细胞的增殖、迁移、侵袭。

关键词: 长链非编码RNA含有5个PH结构域的反义RNA1, 微小RNA-299-5p, 组蛋白赖氨酸残基去甲基化酶4B, 大肠癌, 增殖, 迁移, 侵袭

Abstract: Objective To investigate the impacts of long non coding RNA (LncRNA)PH domain containing 5 antisense RNA 1 (FGD5-AS1) on the proliferation,migration,and invasion of colorectal cancer (CRC) cells by regulating the miR-299-5p/recombinant lysine specific demethylase 4B (KDM4B) axis.Methods The expressions of LncRNA FGD5-AS1,miR-299-5p,and KDM4B were detected by qRT-PCR in the surgically resected CRC tissues and adjacent tissues of 34 CRC patients CRC cells HCT116 were separated into si-NC group,si-FGD5-AS1 group,si-FGD5-AS1+inhibitor NC group,and si-FGD5-AS1+miR-299-5p inhibitor group.The levels of mRNA in each group were detected.CCK8,scratch assay,and Transwell assay were ap[plied to detect the proliferation,migration,and invasion of HCT116 cells in each group.Western blot was applied to detect the expression of proteins.Dual luciferase reporter gene assay verified the interaction mechanism between LncRNA FGD5-AS1 and miR-299-5p,and between miR-299-5p and KDM4B.Results LncRNA FGD5-AS1 and KDM4B were highly expressed in CRC tissue,while miR-299-5p was low expressed in CRC tissue (P<0.05).The expression of LncRNA FGD5-AS1 mRNA,KDM4B mRNA,OD450,scratch healing rate,invasion number,PCNA,MMP-2,MMP-9,KDM4B in the si-FGD5-AS1 group were lower than those in the si-NC group,the expression of miR-299-5p mRNA was higher than that in the si-NC group (P<0.05).Compared with the si-FGD5-AS1 group and si-FGD5-AS1+inhibitor NC group,the expression of miR-299-5p in the si-FGD5-AS1+miR-299-5p inhibitor group decreased (P<0.05),the KDM4B mRNA,OD450,scratch healing rate,number of invasions,and expression of PCNA,MMP-2,MMP-9,KDM4B increased (P<0.05).LncRNA FGD5-AS1 targeted negative regulation of miR-299-5p,while miR-299-5p targeted negative regulation of KDM4B.Conclusion Knocking down LncRNA FGD5-AS1 may inhibit the proliferation,migration,and invasion of CRC cells,and its mechanism may be achieved by regulating the miR-299-5p/KDM4B signaling axis.

Key words: long non coding RNA PH domain containing 5 antisense RNA 1, micro RNA-299-5p, recombinant lysine specific demethylase 4B, colorectal cancer, proliferation, migration, invasion

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