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

doi:10.16352/j.issn.1001-6325.2026.10.1366

Abstract

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

CLC Number:

R737.9

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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