MiR-33a functions as a tumor suppressor in triple-negative breast cancer by targeting EZH2

Zhang, Weihua; Zou, Guiwei; Cao, Xiaolong; Li, Weizhan

doi:10.1186/s12935-020-1160-z

Cited by 22 publications

(17 citation statements)

References 48 publications

(48 reference statements)

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“…Besides that, this miRNA also arrests the cell cycle in the sub-G0/G1 phase as compared with the other phases, which is in concordance with previous results in lung cancer (8). Recently, some authors suggested that miR-33a can regulate EZH2 by their direct interaction (21). We checked in silico the physical interaction between miR-33b and EZH2 in Targetscan, miRDB-MicroRNA Target Prediction Database, miRNet, miRTarBase, miRanda databases, and the Freiburg RNA tools.…”

Section: Discussionsupporting

confidence: 90%

“…Emerging shreds of evidence also showed that miR-33b negatively regulates MYC in osteosarcoma cancer ( 10 ) and prostate cancer progression ( 9 ) by directly binding with its 3′ UTR region. Moreover, there is recent substantial data which suggested that miR-33a could negatively regulate EZH2 in cancer progression by direct interaction in TNBC ( 21 ).…”

Section: Introductionmentioning

confidence: 99%

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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: Discussionsupporting

confidence: 90%

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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“…For example, it has been revealed that miR33a can suppress the development of TNBC by directly targeting EZH2 to suppress growth and migration and induce G 1 cell-cycle arrest. 15 However, there are few reports about the function of miR497-5p in TNBC.…”

Section: Discussionmentioning

confidence: 99%

Regulatory Effect of miR497-5p–CCNE1 Axis in Triple-Negative Breast Cancer Cells and Its Predictive Value for Early Diagnosis

Liu¹,

Li²,

Zhang³

et al. 2021

CMAR

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Objective: To explore the regulatory role of miR497-5p-CCNE1 axis in triple-negative breast cancer (TNBC) cells and its predictive value for early diagnosis. Methods: Cancer tissue and adjacent tissue samples were collected from 86 patients with TNBC.RT-PCR was used to detect the expression of miR497-5p and CCNE1 (target gene) mRNA, determined by biological prediction in tissue and TNBC cells. ROC was used to analyze the diagnostic value of miR497-5p in TNBC. MTT, invasion, and flow cytometry were used to detect the proliferation, invasion, cycle, apoptosis rate, and expression of related proteins of TNBC cells with overexpression of miR497-5p or knockdown of CCNE1. Results: RT-qPCR results showed that miR497-5p levels were significantly downregulated in TNBC tissue and cells, while CCNE1 expression was significantly upregulated, and miR497-5p expression was negatively correlated with that of CCNE1 (P<0.001). ROC analysis showed that the AUC of miR497-5p for TNBC was >0.9, which had better diagnostic value. The cell tests revealed that miR497-5p played a role in tumor inhibition, including inhibiting proliferation and invasion of TNBC cells, blocking the cell cycle, and promoting apoptosis. Bioinformatic prediction and subsequent experiments revealed that CCNE1 was the direct target of miR497-5p. Furthermore, after knocking down the expression of CCNE1 in TNBC cells, the proliferation and invasion of TNBC cells were significantly inhibited, the cell cycle blocked, and the apoptosis rate significantly increased (P<0.001), and expression of the proapoptosis-related proteins Bax and caspase 3 (cleaved) were upregulated, while expression of the antiapoptosis-related protein BCL2 was downregulated (P<0.001). Conclusion: miR497-5p inhibited the proliferation and invasion of TNBC cells by targeting CCNE1, blocked the cell cycle and promoted the apoptosis of TNBC cells, and had better diagnostic value for TNBC. miR497-5p can be used as a new potential target for the treatment of TNBC.

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“…[ 18 ] Inversely, Xu et al [ 19 ] discovered that miR‐1323 may be regarded as a tumor suppressor and block cell invasion and migration in breast cancer, and overexpression of miR‐33a could restrict breast cancer cells growth and invasion. [ 20 ] Considering studies of the function of miR‐301b in breast cancer, Song et al [ 21 ] reported that miR‐301b promoted cell growth and apoptosis inhibition in triple‐negative breast cancer by targeting CYLD, and miR‐301b was illustrated to be significantly upregulated in triple‐negative breast cancer. [ 22 ] Moreover, Danesh et al [ 23 ] discovered that the miR‐301b rs384262 variant may contribute to elevating the risk of breast cancer in the Iranian population.…”

Section: Discussionmentioning

confidence: 99%

miR‐301b and NR3C2 co‐regulate cells malignant properties and have the potential to be independent prognostic factors in breast cancer

Peng

et al. 2020

J Biochem & Molecular Tox

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This study intends to address the function of miR‐301b/nuclear receptor subfamily 3 group C member 2 (NR3C2) in breast cancer. The Cancer Genome Atlas database was processed to investigate the expression of miR‐301b/NR3C2 in breast cancer samples, as well as the relationship between their expression and the prognosis of the patients. Cox regression analysis was performed to determine whether miR‐301b/NR3C2 was an independent predictor of the patient's prognosis. Associations between miR‐301b and NR3C2 were analyzed by prediction website, dual‐luciferase assay, and Pearson correlation coefficient. Quantitative polymerase chain reaction and Western blot analyses were implemented to detect gene expression. The relevant biological characteristics of MCF7 and BCAP‐37 cells were tested by cell counting kit‐8, colony formation, and transwell assays. Lower expression of NR3C2, which was closely related to the bad prognosis of breast cancer patients, was presented in breast cancer samples and can be used as an independent predictor. miR‐301b, as an upstream regulator of NR3C2, was highly expressed in breast cancer samples and can be used as an independent predictor as well. Notably, a higher level of miR‐301b and lower level of NR3C2 were related to the reduced overall survival in patients with breast cancer. The proliferative and migratory behaviors of cells were elevated or blocked after overexpression of miR‐301b or NR3C2, respectively. However, the above situation was attenuated after together upregulation of miR‐301b and NR3C2. The present data afforded evidence that miR‐301b may be a tumor‐promoting miRNA in breast cancer, and that miR‐301b/NR3C2 axis mediated tumor development from cell proliferation and migration.

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MiR-33a functions as a tumor suppressor in triple-negative breast cancer by targeting EZH2

Cited by 22 publications

References 48 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

Regulatory Effect of miR497-5p–CCNE1 Axis in Triple-Negative Breast Cancer Cells and Its Predictive Value for Early Diagnosis

miR‐301b and NR3C2 co‐regulate cells malignant properties and have the potential to be independent prognostic factors in breast cancer

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