Long non-coding RNA NEAT1 confers oncogenic role in triple-negative breast cancer through modulating chemoresistance and cancer stemness
| العنوان: | Long non-coding RNA NEAT1 confers oncogenic role in triple-negative breast cancer through modulating chemoresistance and cancer stemness |
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| المؤلفون: | Ava Kwong, Man-Ting Siu, Chi-Wang Ho, Vivian Y. Shin, Jiawei Chen, Xian Wang, Isabella Cheuk, Hongchuan Jin |
| المصدر: | Cell Death and Disease, Vol 10, Iss 4, Pp 1-10 (2019) Cell Death & Disease |
| بيانات النشر: | Nature Publishing Group, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Carcinogenesis, medicine.medical_treatment, Transplantation, Heterologous, Immunology, Apoptosis, Triple Negative Breast Neoplasms, Mice, SCID, Article, Targeted therapy, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Breast cancer, SOX2, Mice, Inbred NOD, Cancer stem cell, Cell Line, Tumor, Animals, Humans, Medicine, lcsh:QH573-671, Triple-negative breast cancer, Aged, Cell Proliferation, biology, business.industry, lcsh:Cytology, CD44, Cell Biology, Middle Aged, medicine.disease, G1 Phase Cell Cycle Checkpoints, Gene Expression Regulation, Neoplastic, Transplantation, 030104 developmental biology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, biology.protein, Cancer research, Female, RNA, Long Noncoding, Stem cell, business |
| الوصف: | Triple-negative breast cancer (TNBC) is a malignant subtype of breast cancer with the absence of targeted therapy, resulting in poor prognosis in patients. Chemotherapy remains the mainstay of treatment for TNBC; however, development of drug resistance is the main obstacle for successful treatments. In recent years, long non-coding RNA (lncRNA) has been implicated in multiple biological functions in various diseases, particularly cancers. Accumulating evidence suggested that lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) expression is dysregulated in many human cancers and thus is a useful prognostic marker for cancer patients. Nevertheless, the mechanism of how NEAT1 confers drug resistance in TNBC is still largely unknown. We performed lncRNA profiling by the LncRNA Profiler qPCR Array Kit in normal control (NC) and breast cancers (BC) blood samples and further validated in a larger cohort of samples by qRT-PCR. Gene expression level and localization were investigated by qRT-PCR, western blotting, and immunofluorescence staining. Flow cytometric analysis was carried out to detect cancer stem cells. Functional studies were performed both in vitro and in vivo xenograft model. Among 90 lncRNAs, NEAT1 was highly expressed in the blood samples of breast cancer patients than in NC. In particular, the expression of NEAT1 was higher in TNBC tissues than other subgroups. Functional studies revealed that NEAT1 conferred oncogenic role by regulating apoptosis and cell cycle progression in TNBC cells. We identified that knockdown of NEAT1 sensitized cells to chemotherapy, indicating the involvement in chemoresistance. Importantly, shNEAT1 reduced stem cell populations such as CD44+/CD24−, ALDH+, and SOX2+, implicating that NEAT1 was closely related to cancer stemness in TNBC. Our data highlighted the roles of NEAT1 chemoresistance and cancer stemness, suggesting that it could be used as a new clinical therapeutic target for treating TNBC patients especially those with drug resistance. |
| اللغة: | English |
| تدمد: | 2041-4889 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f6a070f7b1eb6cca8614aa4d9c80e5ddTest http://link.springer.com/article/10.1038/s41419-019-1513-5Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f6a070f7b1eb6cca8614aa4d9c80e5dd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20414889 |
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