microRNA Regulation in Estrogen Receptor-Positive Breast Cancer and Endocrine Therapy

Abstract

As de novo and acquired resistance to standard first line endocrine therapies is a growing clinical challenge for estrogen receptor-positive (ER+) breast cancer patients, understanding the mechanisms of resistance is critical to develop novel therapeutic strategies to prevent therapeutic resistance and improve patient outcomes. The widespread post-transcriptional regulatory role that microRNAs (miRNAs) can have on various oncogenic pathways has been well-documented. In particular, several miRNAs are reported to suppress ERα expression via direct binding with the 3’ UTR of ESR1 mRNA, which can confer resistance to estrogen/ERα-targeted therapies. In turn, estrogen/ERα activation can modulate miRNA expression, which may contribute to ER+ breast carcinogenesis. Given the reported oncogenic and tumor suppressor functions of miRNAs in ER+ breast cancer, the targeted regulation of specific miRNAs is emerging as a promising strategy to treat ER+ breast cancer and significantly improve patient responsiveness to endocrine therapies. In this review, we highlight the major miRNA-ER regulatory mechanisms in context with ER+ breast carcinogenesis, as well as the critical miRNAs that contribute to endocrine therapy resistance or sensitivity. Collectively, this comprehensive review of the current literature sheds light on the clinical applications and challenges associated with miRNA regulatory mechanisms and novel miRNA targets that may have translational value as potential therapeutics for the treatment of ER+ breast cancer.

Genome-wide DNA methylation and expression patterns of microRNAs in relation to breast cancer subtypes among American women of African and European ancestry

“…We identi ed many DMLs that can signi cantly differentiate ER-and ER + tumor subtypes. Some of the top DMLs mapped to, or were in the vicinity of, miRNAs that are differentially expressed in ER-versus ER + tumors, such as multiple CpGs in miR-135b, -190b, and − 224, as shown in our previous study and in other studies (22,30). Many other DMLs were novel relative to ER subtypes, such as CpGs associated with miR-125b1, -2053, -3132, and − 4736.…”

Exosomes of pasteurized milk: potential pathogens of Western diseases

“…Although, epidemiological correlations for whole milk consumption and BC are less established than those for whole milk intake and PCa, tumor-derived exosomes as well play a key role in tumor initiation and progression in BC [344][345][346][347][348][349]. The widespread post-transcriptional regulatory role of miRs is of recent interest in estrogen receptor (ER)-positive BC, comprising about 65%-70% of BCs [350]. Estrogen/ERα activation can modulate miR expression, which may contribute to ER+ breast carcinogenesis [350].…”

“…The widespread post-transcriptional regulatory role of miRs is of recent interest in estrogen receptor (ER)-positive BC, comprising about 65%-70% of BCs [350]. Estrogen/ERα activation can modulate miR expression, which may contribute to ER+ breast carcinogenesis [350]. Estradiol (E2) treatment of BC MCF7 cells doubled the expression levels of miR-148a and miR-21 [351].…”

Comparing MicroRNA Profilings of Purified HER-2-Negative and HER-2-Positive Cells Validates miR-362-5p/Sema3A as Characteristic Molecular Change in Triple-Negative Breast Cancers

“…Comparing the microRNA profiling of HER-2negative and HER-2-positive cells was helpful to understand the molecular mechanism and screen the therapy targets of breast cancer [20][21][22]. Three measures to improve the accuracy of experimental data were made in the present study: first, specific microRNA expression profiling of TNBC and HER-2-overexpressing breast cancer was constructed to ruled out the confounding factors of ER and PR expression states [23][24][25][26]; secondly, tumor parenchymal cells were separated and purified by LCM technology for excluding the bias resulting from microRNA expression of stromal cells [27,28]; thirdly, we investigated the cells come from cancer tissues rather than cell lines because the tumor microenvironment leads to the altered microRNA expression. The expression of 16 microRNAs in TNBC subtype cells was higher than that in HER-2-overexpressing cells, and 5 micro-RNAs were downregulated in TNBC cells.…”