High expression of long non-coding RNA MALAT1 in breast cancer is associated with poor relapse-free survival

Wang, Zhanwei; Katsaros, Dionyssios; Biglia, Nicoletta; Yi, Siyan; Fu, Yuanyuan; Loo, Lenora W. M.; Wang, Jia; Obata, Yuki; Yu, Herbert

doi:10.1007/s10549-018-4839-2

Cited by 63 publications

(58 citation statements)

References 52 publications

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“…In human breast cancer tissues, MALAT1 has been reported to be aberrantly up-regulated and high levels of MALAT1 expression correlate with poor patient prognosis (Chou et al, 2016;Feng et al, 2016;Wang et al, 2018). MALAT1 binds miR-1, miR-124, and miR-448, and acts as a ceRNA to reduce CDC42 and up-regulate CDK4 expression, leading to breast cancer cell cycle progression, cell migration, and invasion (Chou et al, 2016;Feng et al, 2016;Bamodu et al, 2016).…”

Section: The Controversy: Oncogenic and Tumor Suppressive Functions Omentioning

confidence: 99%

The Oncogenic and Tumor Suppressive Functions of the Long Noncoding RNA MALAT1: An Emerging Controversy

2020

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Long noncoding RNAs are recently emerging as critical factors of tumorigenesis. Originally regarded as a pre-messenger RNA (mRNA) splicing regulator, the long noncoding RNA MALAT1 has been demonstrated to regulate gene transcription by binding histone modification enzymes and transcription factors, and to regulate mRNA and protein expression post-transcriptionally by binding microRNAs (miRNAs) and acting as a sponge. Early studies consistently report that MALAT1 is up-regulated in human cancer tissues of various organ origins, particularly metastatic cancer tissues, that high levels of MALAT1 expression in cancer tissues are associated with poor patient prognosis, and that MALAT1 induces cancer cell proliferation, migration, and invasion in vitro and tumor metastasis in mice. By contrast, by analyzing multiple independent large datasets, MALAT1 have very recently been found to be down-regulated in human colorectal and breast cancer tissues, and low MALAT1 expression is associated with decreased patient survival. By binding to the transcription factor TEAD, MALAT1 suppresses metastasis gene expression, colorectal and breast cancer cell migration, invasion, and metastasis in vitro and in mice. MALAT1 has therefore been proposed to function as a tumor suppressor in colorectal and breast cancers. More comprehensive studies with multiple independent cohorts of human cancer tissues of various organ origins, in vitro and in vivo function, and mechanism studies with rescue experiments are required to confirm the oncogenic or tumor suppressive role of MALAT1 in other cancers.

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Section: The Controversy: Oncogenic and Tumor Suppressive Functions Omentioning

confidence: 99%

The Oncogenic and Tumor Suppressive Functions of the Long Noncoding RNA MALAT1: An Emerging Controversy

2020

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“…A previous meta-analysis has shown that the up-regulation of MALAT-1 is significantly correlated with the prognosis and metastasis of cancers [17]. Nevertheless, the prognostic role of MALAT-1 in breast cancer is poorly characterized, with no systematic evaluation conducted to date [18,19]. Therefore, we conducted a systematic review to investigate the associations of MALAT-1 with clinicopathological features and survival of patients with breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Elevated long noncoding RNA MALAT-1 expression is predictive of poor prognosis in patients with breast cancer: a meta-analysis

Wang

Zhang

et al. 2020

Bioscience Reports

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Accumulating evidence indicates that aberrant regulation of metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), a long noncoding RNA, plays a vital role in tumorigenesis. However, its association with breast cancer has not been systematically evaluated. In the current study, a meta-analysis was conducted to clarify the association between MALAT-1 and the prognosis and clinicopathological features of breast cancer. Relevant literature published in several databases was searched. Hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI) were calculated to evaluate the effect of MALAT-1 expression on the survival outcomes and clinicopathological features of breast cancer. A total of 12 studies involving 4,106 patients were identified. Pooled HR demonstrated that elevated MALAT-1 expression significantly predicted unfavorable overall survival (HR=2.06, 95% CI: 1.66–2.56, P<0.0001) in patients with breast cancer. Subgroup analysis stratified by cancer type, sample size, and method of variance analysis also showed statistically significant associations. Additionally, the HR of patients with upregulated MALAT-1 expression concerning disease-free survival, recurrence-free survival, and disease-specific survival was 1.91 (95% CI: 1.53–2.39, P<0.0001). Further, elevated MALAT-1 expression was positively correlated with the progesterone receptor status (OR=1.47, 95% CI: 1.18–1.82). Thus, MALAT-1 is a promising biomarker for predicting survival outcomes in patients with breast cancer.

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“…1a, b). Importantly, one of the identified TROLLs was MALAT1, previously demonstrated to promote different metastatic tumour types in humans [15][16][17] , including breast cancer where high levels of this lncRNA correlate with higher risk of relapse and reduced overall survival [18][19][20] . We performed qRT-PCR and found that 6 TROLLs were upregulated and three were downregulated in TAp63 −/− MECs compared with WT MECs (Fig.…”

Section: Resultsmentioning

confidence: 99%

Pan-cancer analysis reveals TAp63-regulated oncogenic lncRNAs that promote cancer progression through AKT activation

Napoli

Ackerman

et al. 2020

Nat Commun

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The most frequent genetic alterations across multiple human cancers are mutations in TP53 and the activation of the PI3K/AKT pathway, two events crucial for cancer progression. Mutations in TP53 lead to the inhibition of the tumour and metastasis suppressor TAp63, a p53 family member. By performing a mouse-human cross species analysis between the TAp63 metastatic mammary adenocarcinoma mouse model and models of human breast cancer progression, we identified two TAp63-regulated oncogenic lncRNAs, TROLL-2 and TROLL-3. Further, using a pan-cancer analysis of human cancers and multiple mouse models of tumour progression, we revealed that these two lncRNAs induce the activation of AKT to promote cancer progression by regulating the nuclear to cytoplasmic translocation of their effector, WDR26, via the shuttling protein NOLC1. Our data provide preclinical rationale for the implementation of these lncRNAs and WDR26 as therapeutic targets for the treatment of human tumours dependent upon mutant TP53 and/or the PI3K/AKT pathway.

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High expression of long non-coding RNA MALAT1 in breast cancer is associated with poor relapse-free survival

Abstract: High expression of lncRNA MALAT1 is associated with breast cancer relapse and may play a role in tumor progression.

Cited by 63 publications

References 52 publications

The Oncogenic and Tumor Suppressive Functions of the Long Noncoding RNA MALAT1: An Emerging Controversy

The Oncogenic and Tumor Suppressive Functions of the Long Noncoding RNA MALAT1: An Emerging Controversy

Elevated long noncoding RNA MALAT-1 expression is predictive of poor prognosis in patients with breast cancer: a meta-analysis

Pan-cancer analysis reveals TAp63-regulated oncogenic lncRNAs that promote cancer progression through AKT activation

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