GSE173816 MicroRNA-200c/141 confines ER α  activity and expression pattern by targeting Ccnd1 [single-cell RNA-seq]

Contributor : Ting WuSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusER α is one of the most important transcription factors and therapeutic targets in breast cancer. The patterns of ERα expression in normal breast tissue and cancerous lesions are strikingly different. What drives the change of ERα pattern during lesions formation remains unclear. Here, we describe a novel regulatory mechanism through which miR-200c/141 regulates the level as well as the distribution of ERα in the mammary gland. miR-200c/141 is specifically expressed in luminal cells. Luminal-deletion of miR-200c/141 (miR-cKO) leads to a drastic expansion of ERα+ cell proportion. Single ce ll RNAseq reveals that miR-cKO generates aberrant luminal subpopulations with increased proliferative and anti-apoptotic features. In vivo lineage tracing of ER- luminal cells demonstrates that miR-200c/141 deletion can convert ER- cells into ER+ cells, which contribute partly to the increase of ERα+ luminal cells. Mechanistic study identifies  Ccnd1  as a novel target of miR-200c/141 .  Upon miR-200c/141deletion, elevated  Ccnd1  level corroborates ERα transcriptional activation, leads to enhanced ERα signaling activity, consequently increased transcription of ERα coding gene  Esr1  through self-activation at promoter E1. Our findings reveal a new miR-200c/141-Ccnd1-ERα axis, and provide new molecular insights into how miR-200c/141-Ccnd1 enforces the lineag...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research