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

Abstract

Background. HER-2 is a key molecule serving as the therapeutic target, prognostic biomarker, and classification marker in breast cancer. Accurate microRNA profilings had not been conducted in purified tumor cells of HER-2-negative and HER-2-positive tissue specimens obtained from breast cancer patients. Methods. (i) Differential expression microRNA discovery using laser capture microdissection- (LCM-) assisted specimen preparation and microRNA array chips on HER-2 overexpressing and triple-negative breast carcinoma (TNBC) subtype tissues, (ii) differential expression microRNA validation by quantitative real-time PCR, and (iii) independent validation on tissue microarray. Results. Five microRNAs (miR-20a-5p, miR-221-3p, miR-362-5p, miR-502-3p, and miR-222-3p) were screened and validated as upregulated microRNAs in TNBC cells comparing to HER-2 overexpressing cells using a microRNA array (5 cases in each group) and quantitative real-time PCR (20 cases in each group). The expression difference of miR-362-5p had the most significant statistical significance (p=0.0016) among the five microRNAs. The expression of miR-362-5p and its target gene Sema3A was further analyzed using in situ hybridization (ISH) and immunohistochemistry on standard tissue sections (n=150). 70.8% of HER-2-negative cells showed moderate expression of miR-362-5p whereas 20.4% HER-2-negative cells correlated with strong expression of miR-362-5p (p<0.0001). The proportion of patients with moderate/strong miR-362-5p expression in luminal, HER-2 overexpressing, and TNBC subtypes were 53.2%, 22.2%, and 74.3%, respectively (p=0.0002). High miR-362-5p expressers had shorter overall survival in the univariate analysis (p=0.046). There was a significant negative correlation between miR-362-5p and Sema3A expression (p<0.0001). The patients with negative/weak Sema3A protein expression had poorer prognosis than those with moderate (HR: 3.723, p=0.021) or strong (HR: 3.966, p=0.013) Sema3A protein expression in the multivariate analysis. Conclusions. miR-362-5p/Sema3A might provide a promising therapeutic pathway and represents a candidate therapeutic target of the TNBC subtype.

Downregulation hsa_circ_0006620 inhibit the malignant progression of prostate cancer by regulation miR-502-3p/HK2 axis mediated aerobic glycolysis

“…The present study employed bioinformatics analysis to examine whether hsa_circ_0006620 acted with miR-502-3p, which we validated through luciferase report analysis. Former studies found that high miR-502-3p expression reduced migration, invasion, and proliferation abilities in different cancers, such as colorectal cancer, gastric cancer, osteosarcoma, breast cancers and lung cancers [16][17][18][19][20]. Previous study also found that miR-502 play an important role in the progress of prostate cancer [21].…”

Modulatory Role of microRNAs in Triple Negative Breast Cancer with Basal-Like Phenotype

“…EMT; cancer stem cell-like property; cytoskeleton reorganization [148,154] Cell proliferation, migration, and invasion [162] miR-155 TSPAN5 Promotion of stem cell proliferation and cellular proliferation [18,163] miR-150 [18] miR-142-5p miR-142-3p PTEN Cell proliferation and apoptosis [18,75,164,165] miR-135b…”