WGCNA-derived lncRNA MAP3K4-AS1 regulates apoptosis and cell cycle in TNBC MDA-MB-231 cells validated by siRNA knockdown.

TNBC is a crucial therapeutic challenge owing to its aggressiveness and lack of targeted treatments. LncRNAs, vital regulators of gene expression with diverse roles in cancer development, are being explored through high-throughput sequencing and bioinformatics analysis to detect potential biomarkers and therapeutic targets. Current research aims to identify novel lncRNAs and their roles in TNBC using this bioinformatics approach, validated by in vitro analysis. The NCBI GEO dataset and the WGCNA package were used to identify lncRNAs in TNBC. Subsequently, in vitro validation included cell culture, siRNA transfection, MTT assay, apoptosis and cell cycle assays, colony and wound healing assays, and statistical analysis was performed. Also, the expression levels of BAX, BCL2, caspase 3, caspase 8, caspase 9, MMP3, MMP9, and CD44 was assessed using qRT-PCR. Bioinformatics analysis identified MAP3K4-AS1 as a highly correlated lncRNA with TNBC progression. Experimental validation revealed that MAP3K4-AS1 was upregulated in TNBC cell line, MDA-MB-231. siRNA-mediated knockdown of MAP3K4-AS1 significantly reduced cell viability, increased apoptosis, induced cell cycle arrest, and inhibited migration and invasion of MDA-MB-231 cells. This effect was associated with altered expression levels of apoptosis-related genes, matrix metalloproteinases, and CD44. While MAP3K4-AS1 was noted in a few studies, its function remains largely uncharacterized; this study presents the first comprehensive investigation of MAP3K4-AS1 in TNBC, revealing its oncogenic role, and proposing it as a novel therapeutic target.