CHRNA5 belongs to the secondary estrogen signaling network exhibiting prognostic significance in breast cancer

Cholinergic signals can be important modulators of cellular signaling in cancer. We recently have shown that knockdown nicotinic acetylcholine receptor subunit alpha 5, CHRNA5, diminishes the proliferative potential breast cancer cells. However, modulation CHRNA5 expression context estrogen and its prognostic implications remained unexplored. Meta-analyses large microarray cohorts were used to evaluate association with (E2) treatment, (ER) status patient prognosis. The results validated through RT-qPCR analyses multiple E2 treated cell lines, depleted MCF7 cells across a cDNA panel. also calculated predicted secondary (PS) score representing direct/indirect induction gene by based on public dataset (GSE8597). Co-expression analysis was performed using weighted co-expression network (WGCNA) pipeline. Multiple other publicly available datasets such as CCLE, COSMIC TCGA analyzed. Herein we found induced dose- time-dependent manner lines. ER− tumors exhibited higher levels than ER+ tumors. Independent meta-analysis for survival outcome revealed associated worse prognosis untreated patients. Furthermore, co-expressed emerged secondarily targets stimulation. These largely downregulated exposure siRNA while response primary ESR1 dependent direction PS-score. Moreover, target genes uncoupled clustered distinctly datasets. Our findings strongly associate increased