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Comparing MicroRNA Profilings of Purified HER-2-Negative and HER-2-Positive Cells Validates miR-362-5pSema3A as Characteristic Molecular Change in Triple-Negative Breast Cancers
Joint Authors
Fan, Junwei
Zhang, Xiaoqing
He, Qi
Sun, Leiqin
Zhang, Yanfei
Qin, Shengying
Wang, Jianfeng
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-12-18
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Zhang, Xiaoqing& He, Qi& Sun, Leiqin& Zhang, Yanfei& Qin, Shengying& Fan, Junwei…[et al.]. 2019. Comparing MicroRNA Profilings of Purified HER-2-Negative and HER-2-Positive Cells Validates miR-362-5pSema3A as Characteristic Molecular Change in Triple-Negative Breast Cancers. Disease Markers،Vol. 2019, no. 2019, pp.1-12.
https://search.emarefa.net/detail/BIM-1147515
Modern Language Association (MLA)
Zhang, Xiaoqing…[et al.]. Comparing MicroRNA Profilings of Purified HER-2-Negative and HER-2-Positive Cells Validates miR-362-5pSema3A as Characteristic Molecular Change in Triple-Negative Breast Cancers. Disease Markers No. 2019 (2019), pp.1-12.
https://search.emarefa.net/detail/BIM-1147515
American Medical Association (AMA)
Zhang, Xiaoqing& He, Qi& Sun, Leiqin& Zhang, Yanfei& Qin, Shengying& Fan, Junwei…[et al.]. Comparing MicroRNA Profilings of Purified HER-2-Negative and HER-2-Positive Cells Validates miR-362-5pSema3A as Characteristic Molecular Change in Triple-Negative Breast Cancers. Disease Markers. 2019. Vol. 2019, no. 2019, pp.1-12.
https://search.emarefa.net/detail/BIM-1147515
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1147515