miR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer
| العنوان: | miR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer |
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| المؤلفون: | Yao Lung Kuo, Hong Tai Chang, Yu Chia Chen, Pei Jung Lu, Luo Ping Ger, Marcus J. Calkins, Jui Lin Liang, Hao Yi Li, Tai I. Hsu, Michael Hsiao, Hao Hsien Lee, Forn Chia Lin |
| المصدر: | Breast Cancer Research : BCR Breast Cancer Research, Vol 19, Iss 1, Pp 1-14 (2017) |
| بيانات النشر: | BioMed Central, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, miR-93-3p, Antineoplastic Agents, Triple Negative Breast Neoplasms, Kaplan-Meier Estimate, medicine.disease_cause, lcsh:RC254-282, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Surgical oncology, microRNA, medicine, Biomarkers, Tumor, Humans, Triple negative breast cancer, Circulating MicroRNA, Neoplasm Metastasis, Wnt Signaling Pathway, Triple-negative breast cancer, Neoplasm Staging, business.industry, Wnt signaling pathway, miR-105, Biomarker, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Prognosis, MicroRNAs, 030104 developmental biology, ROC Curve, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Drug resistance, Case-Control Studies, Cancer research, Biomarker (medicine), Female, Cisplatin, Neoplasm Grading, Carcinogenesis, business, Transcriptome, Research Article |
| الوصف: | Background Triple negative breast cancer (TNBC) lacks both early detection biomarkers and viable targeted therapeutics. Moreover, chemotherapy only produces 20–30% pathologic complete response. Because miRNAs are frequently dysregulated in breast cancer and have broad tissue effects, individual or combinations of circulating miRNAs may serve as ideal diagnostic, predictive or prognostic biomarkers, as well as therapeutic targets. Understanding the role and mechanism of dysregulated miRNAs in TNBC may help to develop novel diagnostic and prognostic strategy for TNBC patients. Methods The miRNA array profiles of 1299 breast cancer patients were collected from the Metabric database and subjected to analysis of the altered miRNAs between TNBC and non-TNBC. In Student’s t-test and Kaplan-Meier analysis, four upregulated miRNAs correlated with poor survival in TNBC but not in non-TNBC. Four miRNAs were manipulated in multiple cell lines to investigate their functional role in carcinogenesis. From these results, we studied miR-105 and miR-93-3p in greater detail. The level of miR-105 and miR-93-3p were evaluated in 25 breast cancer tumor tissues. In addition, the diagnostic utility of circulating miR-105 and miR-93-3p were examined in 12 normal and 118 breast cancer plasma samples by ROC curve construction. Results miR-105 and miR-93-3p were upregulated and correlated with poor survival in TNBC patients. Both miR-105 and miR-93-3p were found to activate Wnt/β-catenin signaling by downregulation of SFPR1. By this action, stemness, chemoresistance, and metastasis were promoted. Importantly, the combination of circulating miR-105/93-3p may serve as a powerful biomarker for TNBC, even in early-stage disease. Conclusions miR-105/93-3p activates Wnt/β-catenin signaling by downregulating SFRP1 and thereby promotes stemness, chemoresistance, and metastasis in TNBC cells. Most importantly, combined circulating miR-105/93-3p levels represent a prime candidate for development into a diagnostic biomarker for both early- and late-stage TNBC. Electronic supplementary material The online version of this article (doi:10.1186/s13058-017-0918-2) contains supplementary material, which is available to authorized users. |
| اللغة: | English |
| تدمد: | 1465-542X 1465-5411 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f74951fdd41e98fd0e24ca79fddc3447 http://europepmc.org/articles/PMC5738224 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f74951fdd41e98fd0e24ca79fddc3447 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 1465542X 14655411 |
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