Functional Relationships between Long Non-Coding RNAs and Estrogen Receptor Alpha: A New Frontier in Hormone-Responsive Breast Cancer Management

Abstract

In the complex and articulated machinery of the human genome, less than 2% of the transcriptome encodes for proteins, while at least 75% is actively transcribed into non-coding RNAs (ncRNAs). Among the non-coding transcripts, those ≥200 nucleotides long (lncRNAs) are receiving growing attention for their involvement in human diseases, particularly cancer. Genomic studies have revealed the multiplicity of processes, including neoplastic transformation and tumor progression, in which lncRNAs are involved by regulating gene expression at epigenetic, transcriptional, and post-transcriptional levels by mechanism(s) that still need to be clarified. In breast cancer, several lncRNAs were identified and demonstrated to have either oncogenic or tumor-suppressive roles. The functional understanding of the mechanisms of lncRNA action in this disease could represent a potential for translational applications, as these molecules may serve as novel biomarkers of clinical use and potential therapeutic targets. This review highlights the relationship between lncRNAs and the principal hallmark of the luminal breast cancer phenotype, estrogen receptor α (ERα), providing an overview of new potential ways to inhibit estrogenic signaling via this nuclear receptor toward escaping resistance to endocrine therapy.

Long noncoding RNA NONHSAT160169.1 promotes resistance via hsa-let-7c-3p/SOX2 axis in gastric cancer

“…The HGC-27 cell line has been widely used in studies on gastric cancer progression, improvements in therapeutic strategies, and drug resistance 14 – 16 . HGC-27-LR cells were established using a classical approach to subjecting cells to long-term drug gradient pressure in vitro 9 . Subsequently, CCK-8 analysis was performed to determine any potential alterations in the sensitivity of HGC-27 cells to lapatinib.…”

“…The association between long non-coding RNAs and drug resistance in tumor-targeted therapy is currently a hot topic of research 9 – 11 . LncRNAs are aberrantly expressed at different stages of gastric cancer progression, and a few studies have reported mechanisms by which lncRNAs regulate lapatinib-induced drug resistance in gastric cancer; hence, lncRNAs associated with drug resistance may potentially be targeted for personalized therapeutic strategies 11 – 13 .…”

The functional role of lncRNAs as ceRNAs in both ovarian processes and associated diseases

“…What distinguishes them is their substantial length, often exceeding 200 nucleotides. Remarkably, lncRNAs constitute a major portion of the ncRNA landscape, accounting for a substantial percentage, typically ranging from 80 % to 90 % of all ncRNAs [ 9 ]. Their abundance underscores their importance in cellular processes.…”