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Article: Long non-coding RNA NEAT1 confers oncogenic role in triple-negative breast cancer through modulating chemoresistance and cancer stemness

TitleLong non-coding RNA NEAT1 confers oncogenic role in triple-negative breast cancer through modulating chemoresistance and cancer stemness
Authors
Issue Date2019
PublisherNature Publishing Group: Open Access Journals - Option C. The Journal's web site is located at http://www.nature.com/cddis/index.html
Citation
Cell Death & Disease, 2019, v. 10, p. 270 How to Cite?
AbstractTriple-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.
Persistent Identifierhttp://hdl.handle.net/10722/269469
ISSN
2023 Impact Factor: 8.1
2023 SCImago Journal Rankings: 2.447
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorShin, VY-
dc.contributor.authorChen, J-
dc.contributor.authorCheuk, WYI-
dc.contributor.authorSiu, JMT-
dc.contributor.authorHO, CWJ-
dc.contributor.authorWang, X-
dc.contributor.authorJin, HC-
dc.contributor.authorKwong, A-
dc.date.accessioned2019-04-24T08:08:21Z-
dc.date.available2019-04-24T08:08:21Z-
dc.date.issued2019-
dc.identifier.citationCell Death & Disease, 2019, v. 10, p. 270-
dc.identifier.issn2041-4889-
dc.identifier.urihttp://hdl.handle.net/10722/269469-
dc.description.abstractTriple-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.-
dc.languageeng-
dc.publisherNature Publishing Group: Open Access Journals - Option C. The Journal's web site is located at http://www.nature.com/cddis/index.html-
dc.relation.ispartofCell Death & Disease-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleLong non-coding RNA NEAT1 confers oncogenic role in triple-negative breast cancer through modulating chemoresistance and cancer stemness-
dc.typeArticle-
dc.identifier.emailShin, VY: vyshin@hku.hk-
dc.identifier.emailChen, J: gary0526@hku.hk-
dc.identifier.emailCheuk, WYI: isacheuk@hku.hk-
dc.identifier.emailSiu, JMT: jensiu@hku.hk-
dc.identifier.emailKwong, A: avakwong@hku.hk-
dc.identifier.authorityShin, VY=rp02000-
dc.identifier.authorityKwong, A=rp01734-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41419-019-1513-5-
dc.identifier.scopuseid_2-s2.0-85063348835-
dc.identifier.hkuros297452-
dc.identifier.hkuros301040-
dc.identifier.hkuros304851-
dc.identifier.volume10-
dc.identifier.spage270-
dc.identifier.epage270-
dc.identifier.isiWOS:000462414700001-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl2041-4889-

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