miR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer
Abstract 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, indivi...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-12-01
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| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13058-017-0918-2 |
| _version_ | 1818413093523292160 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Hao-Yi Li |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-14T10:57:43Z |
| format | Article |
| id | doaj.art-1554c9dc505642a5aaf7604114037110 |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-12-14T10:57:43Z |
| publishDate | 2017-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-1554c9dc505642a5aaf76041140371102022-12-21T23:04:52ZengBMCBreast Cancer Research1465-542X2017-12-0119111410.1186/s13058-017-0918-2miR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancerHao-Yi Li0Jui-Lin Liang1Yao-Lung Kuo2Hao-Hsien Lee3Marcus J. Calkins4Hong-Tai Chang5Forn-Chia Lin6Yu-Chia Chen7Tai-I Hsu8Michael Hsiao9Luo-Ping Ger10Pei-Jung Lu11Institute of Clinical Medicine, College of Medicine, National Cheng Kung UniversityInstitute of Clinical Medicine, College of Medicine, National Cheng Kung UniversityDepartment of General Surgery, National Cheng Kung University HospitalDepartment of General Surgery, Chi-Mei Medical CenterInstitute of Clinical Medicine, College of Medicine, National Cheng Kung UniversityDepartment of Surgery, Kaohsiung Veterans General HospitalDepartment of Radiation Oncology, National Cheng Kung University HospitalDivision of General Surgery, Department of Surgery, Kaohsiung Veterans General HospitalDepartment of Orthopedics, National Cheng Kung University HospitalGenomics Research Center, Academia SinicaDepartment of Medical Education and Research, Kaohsiung Veterans General HospitalInstitute of Clinical Medicine, College of Medicine, National Cheng Kung UniversityAbstract 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.http://link.springer.com/article/10.1186/s13058-017-0918-2miR-105miR-93-3pBiomarkerCisplatinDrug resistanceTriple negative breast cancer |
| spellingShingle | 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 miR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer Breast Cancer Research miR-105 miR-93-3p Biomarker Cisplatin Drug resistance Triple negative breast cancer |
| title | miR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer |
| title_full | miR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer |
| title_fullStr | miR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer |
| title_full_unstemmed | miR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer |
| title_short | miR-105/93-3p promotes chemoresistance and circulating miR-105/93-3p acts as a diagnostic biomarker for triple negative breast cancer |
| title_sort | mir 105 93 3p promotes chemoresistance and circulating mir 105 93 3p acts as a diagnostic biomarker for triple negative breast cancer |
| topic | miR-105 miR-93-3p Biomarker Cisplatin Drug resistance Triple negative breast cancer |
| url | http://link.springer.com/article/10.1186/s13058-017-0918-2 |
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