Abstract | BACKGROUND: 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.
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Authors | Hao-Yi Li, Jui-Lin Liang, Yao-Lung Kuo, Hao-Hsien Lee, Marcus J Calkins, Hong-Tai Chang, Forn-Chia Lin, Yu-Chia Chen, Tai-I Hsu, Michael Hsiao, Luo-Ping Ger, Pei-Jung Lu |
Journal | Breast cancer research : BCR
(Breast Cancer Res)
Vol. 19
Issue 1
Pg. 133
(Dec 19 2017)
ISSN: 1465-542X [Electronic] England |
PMID | 29258605
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents
- Biomarkers, Tumor
- Circulating MicroRNA
- MIRN105 microRNA, human
- MIRN93 microRNA, human
- MicroRNAs
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Topics |
- Antineoplastic Agents
(pharmacology)
- Biomarkers, Tumor
- Case-Control Studies
- Circulating MicroRNA
- Drug Resistance, Neoplasm
(genetics)
- Female
- Humans
- Kaplan-Meier Estimate
- MicroRNAs
(blood, genetics)
- Neoplasm Grading
- Neoplasm Metastasis
- Neoplasm Staging
- Prognosis
- ROC Curve
- Transcriptome
- Triple Negative Breast Neoplasms
(diagnosis, drug therapy, genetics, mortality)
- Wnt Signaling Pathway
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