Mining Prognostic Significance of MEG3 in Human Breast Cancer Using Bioinformatics Analysis

Cui, Xiangrong; Yi, Qiu; Xuan, Jianhua; Huang, Yue; Tian, Jie; Chen, Long; Xiang, Zhongping; Liu, Jianping; Zhang, Chunmin; Tan, Bin; Li, Yasha; Zhu, Jing

doi:10.1159/000493956

Cited by 35 publications

(32 citation statements)

References 40 publications

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“…Moreover, EPB41L4A-AS2 was also reported to inhibit proliferation and invasion and promote cell apoptosis in non-small cell lung cancer [39], in accordance with our results. Among the other identified lncRNAs, MEG3 was reported to suppress cell proliferation, invasion, and angiogenesis through the AKT pathway or the transcriptional activity of p53 in breast cancer [23–25, 40, 41]. LINC-PINT, which is regulated by p53, inhibits tumor cell invasion through a highly conserved sequence element [42, 43].…”

Section: Discussionmentioning

confidence: 99%

Landscape of tumor suppressor long noncoding RNAs in breast cancer

Pang

Wang

Ning

et al. 2019

J Exp Clin Cancer Res

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Background The landscape and biological functions of tumor suppressor long noncoding RNAs in breast cancer are still unknown. Methods Data from whole transcriptome sequencing of 33 breast specimens in the Harbin Medical University Cancer Center cohort and The Cancer Genome Atlas was applied to identify and validate the landscape of tumor suppressor long noncoding RNAs, which was further validated by The Cancer Genome Atlas pancancer data including 33 cancer types and 12,839 patients. Next, the expression model, prognostic roles, potential biological functions and epigenetic regulation of tumor suppressor long noncoding RNAs were investigated and validated in the breast cancer and pancancer cohorts. Finally, EPB41L4A-AS2 was selected to validate our novel finding, and the tumor suppressive roles of EPB41L4A-AS2 in breast cancer were examined. Results We identified and validated the landscape of tumor suppressor long noncoding RNAs in breast cancer. The expression of the identified long noncoding RNAs was downregulated in cancer tissue samples compared with normal tissue samples, and these long noncoding RNAs correlated with a favorable prognosis in breast cancer patients and the patients in the pancancer cohort. Multiple carcinogenesis-associated biological functions were predicted to be regulated negatively by these long noncoding RNAs. Moreover, these long noncoding RNAs were transcriptionally regulated by epigenetic modification, including DNA methylation and histone methylation modification. Finally, EPB41L4A-AS2 inhibited breast cancer cell proliferation, migration and invasion and induced cell apoptosis in vitro . Mechanistically, EPB41L4A-AS2, acting at least in part as a tumor suppressor, upregulated tumor suppressor gene expression. Moreover, ZNF217 recruited EZH2 to the EPB41L4A-AS2 locus and suppressed the expression of EPB41L4A-AS2 by epigenetically increasing H3K27me3 enrichment. Conclusions This work enlarges the functional landscape of known long noncoding RNAs in human cancer and provides novel insights into the suppressive roles of these long noncoding RNAs. Electronic supplementary material The online version of this article (10.1186/s13046-019-1096-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Landscape of tumor suppressor long noncoding RNAs in breast cancer

Pang

Wang

Ning

et al. 2019

J Exp Clin Cancer Res

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“…Breast cancer is one of the most common malignancies and remains a leading cause of cancer-related deaths in the female worldwide 1 . The incidence of breast cancer is gradually increasing in most countries, including the United States 2 .…”

Section: Introductionmentioning

confidence: 99%

High Expression of Pseudogene PTTG3P Indicates a Poor Prognosis in Human Breast Cancer

Lou

Ding

Fan

2019

Molecular Therapy - Oncolytics

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Pseudogenes play pivotal roles in tumorigenesis. Previous studies have suggested that pituitary tumor-transforming 3, pseudogene (PTTG3P), serves as an oncogene in human cancers. However, its expression pattern, biological function, and underlying mechanism in breast cancer remain unknown. In this study, we demonstrated an elevated expression of PTTG3P in breast cancer and discovered that PTTG3P expression correlated negatively with estrogen receptor (ER) and progesterone receptor (PR) status, but linked positively to basal-like status, triplenegative breast cancer status, Nottingham prognostic index (NPI), and Scarff-Bloom-Richardson grade. High expression of PTTG3P was also found to be associated with a poor prognosis of breast cancer. To explore the potential mechanisms of PTTG3P, a PTTG3P-microRNA (miRNA)-mRNA regulatory network was established. Co-expressed genes of PTTG3P were also obtained. Enrichment analysis for these co-expressed genes revealed that they were significantly enriched in mitotic nuclear division and cell cycle. Subsequent research on mechanism of PTTG3P indicated that its expression correlated positively with PTTG1 expression. However, no significant expression correlation between PTTG3P and PTTG2 was observed. Taken together, our findings suggest that increased expression of pseudogene PTTG3P may be used as a promising prognostic biomarker and novel therapeutic target for breast cancer.

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“…Therefore, it is urgent to enroll a strong prognostic index to facilitate accurate predictions regarding the survival and/or response to the treatment of BC patients [ 44 , 45 ]. In this study, we evaluated the significance of MCM2 as a prognostic marker in BC prediction using bioinformatics [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Computational assessment of MCM2 transcriptional expression and identification of the prognostic biomarker for human breast cancer

Samad¹,

Haque

Nain

et al. 2020

Heliyon

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Minichromosome maintenance protein 2 (MCM2) is a highly conserved protein from the MCM protein family that plays an important role in eukaryotic DNA replication as well as in cell cycle progression. In addition, it maintains the ploidy level consistency in eukaryotic cells, hence, mutations or alteration of this protein could result in the disintegration of the fine-tuned molecular machinery that can lead to uncontrolled cell proliferation. Moreover, MCM2 has been found to be an important marker for progression and prognosis in different cancers. Therefore, we aimed to analyze the MCM2 expression and the associated outcome in breast cancer (BC) patients based on the publicly available online databases. In this study, server-based gene expression analyses indicate the upregulation of MCM2 ( p < 10 −6 ; fold change>2.0) in various BC subtypes as compared to the respective normal tissues. Besides, the evaluation of histological sections from healthy and cancer tissues showed strong staining signals indicating higher expression of MCM2 protein. The overexpression of MCM2 was significantly correlated to promoter methylation and was related to patients' clinical features. Further, mutation analysis suggested missense as the predominant type of mutation (71.4%) with 18 copy-number alterations and 0.2% mutation frequency in the MCM2 gene. This study revealed a significant correlation (Cox p ≤ 0.05) between the higher MCM2 expression and lower patient survival. Finally, we identified the co-expressed genes with gene ontological features and signaling pathways associated in BC development. We believe that this study will provide a basis for MCM2 to be a significant biomarker for human BC prognosis.

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Mining Prognostic Significance of MEG3 in Human Breast Cancer Using Bioinformatics Analysis

Cited by 35 publications

References 40 publications

Landscape of tumor suppressor long noncoding RNAs in breast cancer

Landscape of tumor suppressor long noncoding RNAs in breast cancer

High Expression of Pseudogene PTTG3P Indicates a Poor Prognosis in Human Breast Cancer

Computational assessment of MCM2 transcriptional expression and identification of the prognostic biomarker for human breast cancer

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