剪接体LSM4通过调控DNA损伤修复途径抑制三阴性乳腺癌细胞MDA-MB-231恶性进展

doi:10.16352/j.issn.1001-6325.2026.10.1366

基础医学与临床 ›› 2026, Vol. 46 ›› Issue (10): 1366-1374.doi: 10.16352/j.issn.1001-6325.2026.10.1366

剪接体LSM4通过调控DNA损伤修复途径抑制三阴性乳腺癌细胞MDA-MB-231恶性进展

孜那提·努尔太^1,2, 柔倩², 张梦², 刘莹², 成芳^2*

1.新疆医科大学医学科学研究所,新疆乌鲁木齐 830017;
2.新疆医科大学附属肿瘤医院综合特需科,新疆乌鲁木齐 830000

收稿日期:2025-10-11 修回日期:2025-12-30 出版日期:2026-10-05 发布日期:2026-09-18
通讯作者: ^*luckychengfang@126.com
基金资助:
新疆医科大学医学科学研究所开放课题(YXYJ20240304)

Spliceosome LSM4 inhibits the malignant progression of triple-negative breast cancer cell MDA-MB-231 through regulating DNA damage repair pathway

Zinati·NUERTAI^1,2, ROU Qian², ZHANG Meng², LIU Ying², CHENG Fang^2*

1. Institute of Medical Sciences, Xinjiang Medical University, Urumqi 830017;
2. Comprehensive VIP Department, Xinjiang Medical University Affiliated Tumor Hospital, Urumqi 830000, China

Received:2025-10-11 Revised:2025-12-30 Online:2026-10-05 Published:2026-09-18
Contact: ^*luckychengfang@126.com

摘要/Abstract

摘要： 目的探索剪接体蛋白LSM4在三阴性乳腺癌(TNBC)中的生物学功能及潜在的调控机制。方法使用癌基因组图谱(TCGA)和临床蛋白质组学肿瘤分析协会(CPTAC)样本分析LSM4在TNBC中的mRNA和蛋白表达水平,采用小干扰RNA(siRNA)在MDA-MB-231细胞中瞬时敲低LSM4,CCK-8法检测细胞增殖,Annexin V/PI法检测细胞凋亡,Transwell实验检测细胞的侵袭和迁移,转录组测序(RNA-seq)分析LSM4调控的差异表达基因和可变剪接事件。结果 LSM4在TNBC患者中表达失调,体外敲低LSM4后可显著促进MDA-MB-231细胞的增殖、侵袭和迁移能力,并抑制细胞凋亡,LSM4调控的可变剪接基因主要富集在与DNA损伤修复相关的信号途径上,特别是参与调节DNA聚合酶β(POLB)的外显子互斥和跳跃事件,可能促使其生成非编码蛋白或编码较短蛋白的转录本异构体,从而影响癌细胞基因组稳定性。结论 LSM4可能通过激活并调控DNA损伤修复途径相关基因的可变剪接事件从而影响TNBC的发生和发展。

关键词: LSM4, 三阴性乳腺癌, 转录组测序, 可变剪接, DNA损伤与修复

Abstract: Objective To explore the biological functions and potential regulatory mechanisms of spliceosome LSM4 in triple-negative breast cancer (TNBC). Methods The mRNA and protein expression levels of LSM4 in TNBC were analyzed using The Cancer Genome Atlas (TCGA) and Clinical Proteomics Tumor Analysis Consortium (CPTAC) samples, and small interfering RNA (siRNA) was used to transiently knock down LSM4 in MDA-MB-231 cells. CCK-8 assay for cell proliferation, annexin V/PI double staining for apoptosis, Transwell to detect cell invasion and migration, and RNA-seq to analyze the differentially expressed genes and regulated alternative splicing events. Results LSM4 was abnormally expressed in TNBC patients, and knockdown of LSM4 in vitro significantly promoted the proliferation, invasion and migration of MDA-MB-231 cells and inhibited apoptosis. The alternative splicing genes regulated by LSM4 were mainly enriched in the signaling pathways related to DNA damage repair, especially involved in modulating the exon exclusion and skipping events of DNA polymerase β (POLB), possibly promoting the generation of transcript isoforms with non-coding or encoding for a shorter protein, thereby affecting the genomic stability of cancer cells. Conclusions LSM4 might affect the onset and progression of TNBC via activating and modulating alternative splicing events of genes involved in DNA damage repair pathway.

Key words: LSM4, triple negative breast cancer, RNA-seq, alternative splicing, DNA damage and repair

中图分类号:

R737.9

孜那提·努尔太, 柔倩, 张梦, 刘莹, 成芳. 剪接体LSM4通过调控DNA损伤修复途径抑制三阴性乳腺癌细胞MDA-MB-231恶性进展[J]. 基础医学与临床, 2026, 46(10): 1366-1374.

Zinati·NUERTAI, ROU Qian, ZHANG Meng, LIU Ying, CHENG Fang. Spliceosome LSM4 inhibits the malignant progression of triple-negative breast cancer cell MDA-MB-231 through regulating DNA damage repair pathway[J]. Basic & Clinical Medicine, 2026, 46(10): 1366-1374.

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剪接体LSM4通过调控DNA损伤修复途径抑制三阴性乳腺癌细胞MDA-MB-231恶性进展

Spliceosome LSM4 inhibits the malignant progression of triple-negative breast cancer cell MDA-MB-231 through regulating DNA damage repair pathway

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