Harnessing the Role of ESR1 in Breast Cancer: Correlation with microRNA, lncRNA, and Methylation

Breast cancer (BC) is a multifactorial condition and it primarily expresses the estrogen receptor α (ERα) that is encoded by the gene estrogen receptor 1 (<i>ESR1</i>), which modulates estrogen signaling. <i>ESR1</i>, by facilitating estrogen overproduction, plays an indispensable role in the progression and survival of the majority of BCs. To obtain molecular insights into these phenomena, we analyzed The Cancer Genome Atlas (TCGA) breast invasive carcinoma (BRCA) RNA-Seq datasets for the expression of <i>ESR1</i> and its correlation to microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), along with its methylation patterns. Regulation of <i>ESR1</i> was also assessed with a total of 43 cancerous and non-cancerous breast cell lines. Analyses of both TCGA BRCA and breast cell line RNA-Seq data revealed that specific lncRNAs, i.e., MEG3, BIK, MLL, and FAS are negatively correlated with the <i>ESR1</i>, in which PARP1 demonstrates a positive association. Additionally, both miR-30a and miR-145 showed negative correlations with the <i>ESR1</i> expression. Of the 54 <i>ESR1</i> methylation loci analyzed, the majority of them exhibited a negative correlation with the <i>ESR1</i> expression, highlighting a potentially modifiable regulatory mechanism. These findings underscore the complex regulatory events influencing <i>ESR1</i> expression and its interaction with diverse signaling pathways, demonstrating novel insights into breast pathogenesis and its potential therapeutics.