Identification and Roles of miR-29b-1-3p and miR29a-3p-Regulated and Non-Regulated lncRNAs in Endocrine-Sensitive and Resistant Breast Cancer Cells

Abstract

Despite improvements in the treatment of endocrine-resistant metastatic disease using combination therapies in patients with estrogen receptor α (ERα) primary tumors, the mechanisms underlying endocrine resistance remain to be elucidated. Non-coding RNAs (ncRNAs), including microRNAs (miRNA) and long non-coding RNAs (lncRNA), are targets and regulators of cell signaling pathways and their exosomal transport may contribute to metastasis. Previous studies have shown that a low expression of miR-29a-3p and miR-29b-3p is associated with lower overall breast cancer survival before 150 mos. Transient, modest overexpression of miR-29b1-3p or miR-29a-3p inhibited MCF-7 tamoxifen-sensitive and LCC9 tamoxifen-resistant cell proliferation. Here, we identify miR-29b-1/a-regulated and non-regulated differentially expressed lncRNAs in MCF-7 and LCC9 cells using next-generation RNA seq. More lncRNAs were miR-29b-1/a-regulated in LCC9 cells than in MCF-7 cells, including DANCR, GAS5, DSCAM-AS1, SNHG5, and CRND. We examined the roles of miR-29-regulated and differentially expressed lncRNAs in endocrine-resistant breast cancer, including putative and proven targets and expression patterns in survival analysis using the KM Plotter and TCGA databases. This study provides new insights into lncRNAs in endocrine-resistant breast cancer.

Matrix Metalloproteinase-1 (MMP1) Upregulation through Promoter Hypomethylation Enhances Tamoxifen Resistance in Breast Cancer

“…Epigenetic changes, including altered methylation levels at CpG sites that are usually located on the promoters of coding genes, and dysregulation of microRNAs (miRNAs), have been also implicated in several tamR cases [ 18 , 19 ]. Aberrant CpG island methylation has been observed at the promoter of various genes in tamR cancer cells, resulting in dysregulated transcription [ 20 , 21 ].…”

miR‑29a‑3p inhibits the malignant characteristics of non‑small cell lung cancer cells by reducing the activity of the Wnt/β‑catenin signaling pathway

“…miRNAs play important roles in tumor progression through tumor suppressor inactivation or regulation of pertinent pathways ( 31 ). miR-29a-3p has been recognized as a critical miRNA in various types of cancer, and typically functions as a tumor suppressor by directly targeting oncogenic genes ( 29 , 32 – 34 ). miR-29a-3p expression was shown to be downregulated in some cancer types, such as cervical ( 35 ), endometrial ( 13 ), and gastric ( 36 ) cancer, and this downregulation was associated with worse outcomes.…”

Multi-level analysis of adipose tissue reveals the relevance of perivascular subpopulations and an increased endothelial permeability in early-stage lipedema

“…Inhibition of miR-24-3p in circulating exosomes from diabetic foot ulcer patients restores angiogenesis in vitro and in vivo [56]. Estrogen receptor-regulated miRNAs have already been studied in literature to identify prognostic/predictive markers for cancer, amongst which miR-16-5p and miR-29a-3p have been identified [57][58][59]. Therefore, local estradiol as key regulator in lipedema may regulate local tissue cells such as vascular EC via miRNA signaling.…”