基础医学与临床 ›› 2025, Vol. 45 ›› Issue (10): 1298-1305.doi: 10.16352/j.issn.1001-6325.2025.10.1298

• 研究论文 • 上一篇    下一篇

沉默LINC00460通过EZH2抑制人肺腺癌细胞系增殖与迁移

曾慈梅1*, 黄邓高2, 王蕾1, 梁海梅1, 马西淼3   

  1. 中南大学湘雅医学院附属海口医院 1.呼吸与危重症医学科; 2.中心实验室; 3.胸外科,海南 海口 570208
  • 收稿日期:2024-09-13 修回日期:2024-12-31 出版日期:2025-10-05 发布日期:2025-09-22
  • 通讯作者: *3979761185@qq.com
  • 基金资助:
    海南省自然科学基金高层次人才项目(822RC868)

Silencing LINC00460 inhibits proliferation and migration of human lung adenocarcinoma cell lines via EZH2

ZENG Cimei1*, HUANG Denggao2, WANG Lei1, LIANG Haimei1, MA Ximiao3   

  1. 1. Department of Respiratory and Critical Care Medicine; 2. Central Laboratory; 3. Department of Thoracic Surgery, Haikou Hospital Affiliated to Xiangya Medical College, Central South University, Haikou 570208, China
  • Received:2024-09-13 Revised:2024-12-31 Online:2025-10-05 Published:2025-09-22
  • Contact: *3979761185@qq.com

摘要: 目的 探讨长链非编码RNA LINC00460在人肺腺癌(LUAD)细胞系中的表达及其对细胞增殖和迁移的影响。方法 用RT-qPCR检测肺腺癌细胞系(PC-9、A549、NCI-H1975和H1299)及正常肺细胞系(MRC-5)中LINC00460的表达水平;通过siRNA技术沉默A549和H1299细胞中的LINC00460。CCK8检测细胞增殖,Transwell小室法检测细胞迁移;荧光原位杂交和RNA免疫共沉淀确定LINC00460的亚细胞定位及其与EZH2的相互作用;Western blot检测细胞中EZH2及H3K27me3表达。结果 LINC00460在LUAD细胞中高表达,且沉默LINC00460后其表达水平显著降低(P<0.001)。沉默LINC00460显著抑制了A549和H1299细胞的增殖和迁移能力(P<0.001)。LINC00460主要定位于细胞核,可以被EZH2抗体显著富集(P<0.001)。沉默LINC00460后,EZH2及其下游H3K27me3的表达水平显著下降(P<0.001)。结论 LINC00460在LUAD细胞中高表达。沉默LINC00460通过EZH2抑制细胞的增殖和迁移。这一机制为LINC00460作为肺腺癌的潜在治疗靶点提供了依据。

关键词: 肺腺癌, LINC00460, 锌指蛋白同源增强子2, 组蛋白H3第27位赖氨酸的三甲基化

Abstract: Objective To investigate the expression of long non-coding RNA LINC00460 in lung adenocarcinoma (LUAD) and its effects on cell proliferation and migration. Methods Quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression of LINC00460 in LUAD cell lines (PC-9,A549,NCI-H1975 and H1299) and normal lung cell line (MRC-5). LINC00460 was silenced in A549 and H1299 cells using small interfering RNA (siRNA), followed by cell proliferation assessment with CCK-8 assay and evaluation of cell migration capacity through the Transwell assay. Fluorescence in situ hybridization (FISH) and RNA immunoprecipitation (RIP) assays were performed to determine the subcellular localization of LINC00460 and its interaction with EZH2. Western blot was applied to examine EZH2 and H3K27me3 expression in cells. Results LINC00460 was highly expressed in LUAD cells, and the expression level was significantly decreased after silencing (P<0.001). Silencing LINC00460 markedly inhibited the proliferation and migration of A549 and H1299 cells (P<0.001). LINC00460 was primarily localized in the nucleus. RIP assays confirmed a significant interaction between LINC00460 and EZH2 (P<0.001). Furthermore, the silencing of LINC00460 resulted in a significant reduction in the expression of EZH2 and its downstream target H3K27me3 (P<0.001). Conclusions LINC00460 is highly expressed in LUAD cells. Silencing LINC00460 inhibits cell proliferation and migration through EZH2. This mechanism provides a basis for LINC00460 as a potential therapeutic target in lung adenocarcinoma.

Key words: lung adenocarcinoma, LINC00460, EZH2, H3K27me3

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