Overexpression of CDCA7 predicts poor prognosis and induces EZH2‐mediated progression of triple‐negative breast cancer

Ye, Liping; Li, Fengyan; Song, Yipeng; Yu, Dong-Lin; Xiong, Zhenchong; Li, Yue; Shi, Tianyi; Yuan, Zhongyu; Lin, Chuyong; Wu, Xiao; Lang, Ren; Li, Xinghua; Song, Libing

doi:10.1002/ijc.31766

Cited by 49 publications

(42 citation statements)

References 40 publications

(74 reference statements)

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“…EZH2 is overexpressed in metastatic prostate cancer and promotes cell metastasis and proliferation by inhibiting apoptosis (15). It is also described as a master regulator of the EMT by overexpressing Snail, Slug, and vimentin and suppresses E-cadherin (CDH1) expression in endometrial cancer and gastric cancer (16,17), but less has been explored in the HER2+ BC subtype. Moreover, the transcription factor MYC (18) has been suggested as a positive regulator of EZH2 by different mechanisms in several types of cancers.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-33b Suppresses Epithelial–Mesenchymal Transition Repressing the MYC–EZH2 Pathway in HER2+ Breast Carcinoma

et al. 2020

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Downregulation of miR-33b has been documented in many types of cancers and is being involved in proliferation, migration, and epithelial-mesenchymal transition (EMT). Furthermore, the enhancer of zeste homolog 2-gene (EZH2) is a master regulator of controlling the stem cell differentiation and the cell proliferation processes. We aim to evaluate the implication of miR-33b in the EMT pathway in HER2+ breast cancer (BC) and to analyze the role of EZH2 in this process as well as the interaction between them. miR-33b is downregulated in HER2+ BC cells vs healthy controls, where EZH2 has an opposite expression in vitro and in patients' samples. The upregulation of miR-33b suppressed proliferation, induced apoptosis, reduced invasion, migration and regulated EMT by an increase of E-cadherin and a decrease of ß-catenin and vimentin. The silencing of EZH2 mimicked the impact of miR-33b overexpression. Furthermore, the inhibition of miR-33b induces cell proliferation, invasion, migration, EMT, and EZH2 expression in non-tumorigenic cells. Importantly, the Kaplan-Meier analysis showed a significant association between high miR-33b expression and better overall survival. These results suggest miR-33b as a suppressive miRNA that could inhibit tumor metastasis and invasion in HER2+ BC partly by impeding EMT through the repression of the MYC-EZH2 loop.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-33b Suppresses Epithelial–Mesenchymal Transition Repressing the MYC–EZH2 Pathway in HER2+ Breast Carcinoma

et al. 2020

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“…Several of these genes have substantial evidence in the literature of their involvement in breast cancer. For example, it is known that silencing CDCA7 in triple negative breast cancers reduced tumorigenicity and invasion in [74], while the forced expression of GPAA1 in [71] was shown to increase them. PSIP1 has also been shown to directly promote tumorigenicity in breast cancer [59].…”

Section: Resultsmentioning

confidence: 99%

Finding associations in a heterogeneous setting: Statistical test for aberration enrichment

Mezlini

Das

Goldenberg

2020

Preprint

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Most two-group statistical tests are implicitly looking for a broad pattern such as an overall shift in mean, median or variance between the two groups. Therefore, they operate best in settings where the effect of interest is uniformly affecting everyone in one group versus the other. In real-world applications, there are many scenarios where the effect of interest is heterogeneous. For example, a drug that works very well on only a proportion of patients and is equivalent to a placebo on the remaining patients, or a disease associated gene expression dysregulation that only occurs in a proportion of cases whereas the remaining cases have expression levels indistinguishable from the controls for the considered gene. In these examples with heterogeneous effect, we believe that using classical two-group statistical tests may not be the most powerful way to detect the signal. In this paper, we developed a statistical test targeting heterogeneous effects and demonstrated its power in a controlled simulation setting compared to existing methods. We focused on the problem of finding meaningful associations in complex genetic diseases using omics data such as gene expression, miRNA expression, and DNA methylation. In simulated and real data, we showed that our test is complementary to the traditionally used statistical tests and is able to detect disease-relevant genes with heterogeneous effects which would not be detectable with previous approaches.

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“…EZH2 was searched from online bioinformatics database as a potential downstream target for miRNA-101. As an epigenetic regulator, EZH2 is highly expressed in a variety of malignant tumors and associated with poor prognosis of tumors including colorectal cancer,bladder cancer, non-small cell lung cancer [27][28][29].…”

Section: Discussionmentioning

confidence: 99%

LncRNA00518 promotes cell proliferation through regulating miR-101 in bladder cancer

Wang¹,

Ma²,

Tang³

et al. 2020

J. Cancer

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The purpose of our study is to elucidate the expression of lncRNA00518 (lnc00518) in the bladder cancer, and its potential mechanism in regulating the development of bladder cancer. The expression of lnc00518 in bladder cancer tissues and cells was examined by qRT-PCR. Correlation between lnc00518 expression with clinicopathologic characteristics and prognosis of bladder cancer patients was analyzed. In vitro effects of lnc00518 on the cellular behaviors of bladder cancer cells were explored. Moreover, in vivo effect of lnc00518 was evaluated by subcutaneous tumorigenesis in nude mice. The possible miRNA targets of lnc00518 were predicted by bioinformatics and further confirmed by dual-luciferase reporter gene assay, RIP and rescue experiments. Lnc00518 was highly expressed in bladder cancer tissues and cells. Lnc00518 expression was correlated with TNM staging and histological grade of bladder cancer. Besides, the overall survival was lower in bladder cancer patients with high expression of lnc00518 relative to those with low expression. Overexpression of lnc00518 enhanced proliferative, invasive, migratory potentials and clonality, but shortened G0/G1 phase of bladder cancer cells. Lnc00518 knockdown obtained the opposite trends. In vivo experiments revealed that lnc00518 knockdown inhibited subcutaneous tumorigenesis in nude mice. QRT-PCR results indicated that lnc00518 expression was negatively correlated with miRNA-101 expression in bladder cancer cells. Through dual-luciferase reporter gene assay and RIP, we confirmed the binding between lnc00518 and miRNA-101. Furthermore, EZH2 was verified to be the target of miRNA-101. MiRNA-101 knockdown reversed the inhibitory roles of lnc00518 knockdown in proliferative, migratory and invasive potentials of bladder cancer cells. Lnc00518 is highly expressed in bladder cancer and can be served as a predictor of poor prognosis. Lnc00518 promotes the proliferative, invasive and migratory potentials of bladder cancer by upregulating EZH2 via competitively binding to miRNA-101.

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Overexpression of CDCA7 predicts poor prognosis and induces EZH2‐mediated progression of triple‐negative breast cancer

Cited by 49 publications

References 40 publications

MicroRNA-33b Suppresses Epithelial–Mesenchymal Transition Repressing the MYC–EZH2 Pathway in HER2+ Breast Carcinoma

MicroRNA-33b Suppresses Epithelial–Mesenchymal Transition Repressing the MYC–EZH2 Pathway in HER2+ Breast Carcinoma

Finding associations in a heterogeneous setting: Statistical test for aberration enrichment

LncRNA00518 promotes cell proliferation through regulating miR-101 in bladder cancer

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