Dataset Information

Identification of long non-coding RNA signatures in triple-negative breast cancer.

ABSTRACT:

Background

Triple-negative breast cancer (TNBC) is a particular breast cancer subtype with poor prognosis due to its aggressive biological behavior and lack of targets for therapy. This study aimed to explore the expression profile and potential function of lncRNAs in TNBC through bioinformatic methods.

Methods

Two microarrays of TNBC were obtained from the Gene Expression Omnibus database. Differentially expressed lncRNAs and mRNAs were screened out and the expressions of top lncRNAs and overlapping lncRNAs were validated using data from The Cancer Genome Atlas database. The co-expression analysis of lncRNAs and mRNAs was conducted using R software and functional enrichment analysis for was performed by Metascape. Kaplan-Meier Plotter was used for survival analysis.

Results

A total of 1034 dysregulated lncRNAs were found in the two microarrays, and there were 8 overlapped lncRNAs. Among them, 537 lncRNAs were significantly correlated with 451 protein-coding genes (PCGs). The co-expressed PCGs were mainly enriched in terms including cell division, cell cycle, and protein/DNA binding, and were involved in pathways in cancer and other pathways such as PI3K-Akt, MAPK, ErbB and p53 signaling pathways. Hub-genes in the co-expression network were identified, and 7 of them were associated with relapse-free survival of TNBC (MAGI2-AS3: HR?=?0.51; GGTA1P: HR?=?0.54; NAP1L2: HR?=?0.59; CRABP2: HR?=?0.41; SYNPO2: HR?=?0.50; MKI67: HR?=?2.23; COL4A6: HR?=?1.91; all P?ConclusionsNumerous lncRNAs were dysregulated in TNBC, and many of them are possibly involved in cancer biology. Several of these lncRNAs were associated with of TNBC prognosis, which can be promising biomarkers.

SUBMITTER: Tian T

PROVIDER: S-EPMC6050698 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Identification of long non-coding RNA signatures in triple-negative breast cancer.

Tian Tian T Gong Zhouqing Z Wang Meng M Hao Ruohan R Lin Shuai S Liu Kang K Guan Feng F Xu Peng P Deng Yujiao Y Song Dingli D Li Na N Wu Ying Y Dai Zhijun Z

Cancer cell international 20180717

<h4>Background</h4>Triple-negative breast cancer (TNBC) is a particular breast cancer subtype with poor prognosis due to its aggressive biological behavior and lack of targets for therapy. This study aimed to explore the expression profile and potential function of lncRNAs in TNBC through bioinformatic methods.<h4>Methods</h4>Two microarrays of TNBC were obtained from the Gene Expression Omnibus database. Differentially expressed lncRNAs and mRNAs were screened out and the expressions of top lnc ...[more]

PMID: 30026672

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Project description: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.

Dataset Information

Identification of long non-coding RNA signatures in triple-negative breast cancer.

Background

Methods

Results

Publications

Identification of long non-coding RNA signatures in triple-negative breast cancer.

Similar Datasets

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