MicroRNA 34c Gene Down-regulation via DNA Methylation Promotes Self-renewal and Epithelial-Mesenchymal Transition in Breast Tumor-initiating Cells

Yu, Fang; Jiao, Yu; Zhu, Yingting; Wang, Ying; Zhu, Jingde; Cui, Xiaona; Liu, Yujie; He, Yinghua; Park, Eun Young; Zhang, Hongyu; Lv, Xiaobin; Ma, Kelong; Su, Fengxi; Park, Jong Hoon; Song, Erwei

doi:10.1074/jbc.m111.280768

Cited by 136 publications

(123 citation statements)

References 44 publications

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“…29 Numerous studies have shown the dysregulation of miR-34 in various types of cancers, including hepatocellular, mesothelial and colon cancer, melanomas, leukemia, nasopharyngeal cancer, 30 prostate cancer, 31 neuroblastomas, 32 glioblastoma 33 and breast cancer. 34 Yet, little research has been conducted in EC, apart from a functional study by Li et al 35 demonstrating that miR-34c acts as a tumor suppressor in HEC-1-B cells, and that E2F3 protein may be a target of miR-34c.…”

Section: Discussionmentioning

confidence: 99%

Identification of microRNA expression profile related to lymph node status in women with early-stage grade 1–2 endometrial cancer

et al. 2016

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Conventional methods used for histologic classification and grading of endometrial cancer (EC) are not sufficient to predict lymph node metastases. microRNA signatures have recently been related to EC pathologic characteristics or prognosis. The aim of this study was to evaluate whether microRNA profiles of grade 1-2 endometrioid adenocarcinomas can be related to nodal status and used as a tool to adapt surgical staging in early-stage EC. microRNA expression was assessed in nine formalin-fixed paraffin-embedded (FFPE) EC primary tumors with positive lymph node and in 27 FFPE EC primary tumors with negative lymph node, matched for grade, stage, and lymphovascular space involvement status. A microarray analysis showed that there was more than a twofold significant difference in the expression of 12 microRNAs between the two groups. A quantitative reverse transcriptase-PCR assay was used to confirm these results: the expression levels of five microRNAs (microRNA-34c-5p, -375, -184, -34c-3p, and -34b-5p) were significantly lower in the EC primary tumor with positive lymph node compared with those with negative lymph node. A minimal P-value approach revealed that women with a microRNA-375-fold change o 0.30 were more likely to have positive lymph node (n = 8; 53.3%) compared with those with a microRNA-375-fold change 40.30 (n = 1; 4.8%), P = 0.001. Furthermore, women with a microRNA 184-fold change o0.30 were more likely to have positive lymph node (n = 6; 60.0%) compared with those with a microRNA 184-fold change 40.30 (n = 3; 11.5%), P = 0.006. This is the first study investigating the relative expression of mature microRNA genes in early-stage grade 1-2 EC primary tumors according to the nodal status. This microRNA expression profile provides a potential basis for further study of the microRNA function in EC and could be used as a diagnostic tool for nodal status.

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Section: Discussionmentioning

confidence: 99%

Identification of microRNA expression profile related to lymph node status in women with early-stage grade 1–2 endometrial cancer

et al. 2016

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“…The hypermethylation of promoter CpG islands has been found to affect not only tumor-suppressor mRNAs, but also tumor-suppressor miRNAs. Several tumor-associated miRNAs have been reported to be silenced by the aberrant hypermethylation of their promoter regions in breast cancer, including miR-124, miR-34c, miR-148a, miR-155, miR-203 and miR-129 (3,(18)(19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of miR-129-2 by promoter hypermethylation regulates breast cancer cell proliferation and apoptosis

Tang

Liu

et al. 2016

Oncology Reports

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Abstract. Aberrant expression of the miR-129 family has been found in several types of cancer, yet its expression and potential biologic role in breast cancer remain largely unknown. In the present study, we found that miR-129-2 was consistently downregulated in the breast cancer specimens and cell lines. Overexpression of miR-129-2-3p markedly suppressed breast cancer cell proliferation and induced its apoptosis. In addition, a luciferase reporter assay revealed that miR-129-2-3p suppressed BCL2L2 expression. Furthermore, BCL2L2 was able to reverse miR-129-2-3p-mediated cell apoptosis, indicating that BCL2L2 plays a crucial role in mediating the tumor-suppressive role of miR-129-2-3p. Moreover, bisulfite DNA sequencing PCR (BSP) analysis identified that promoter hypermethylation was responsible for the downregulation of miR-129-2 in breast cancer. Collectively, our findings indicate that miR-129-2 is downregulated in breast cancer cells by promoter hypermethylation. Moreover, downregulation of miR-129-2 results in BCL2L2 overexpression and disease progression in breast cancer patients.

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“…Increasing evidence shows that miRNAs can regulate TICs, and aberrant miRNAs in TICs may help in the understanding the mechanism of tumorigenesis, therapyresistance, recurrence, and metastasis (Yu et al, 2010;Wu et al, 2012;Yu et al, 2012;Kwon and Shin, 2013). miR-155 plays an important role in various physiological and pathological processes (Faraoni et al, 2009;Elton et al, 2012) and has been found to be upregulated in several solid tumors, such as clear-cell kidney cancer (Juan et al, 2010), hepatocellular carcinoma (Wang et al, 2009a), breast cancer (Jiang et al, 2010;Kong et al, 2010), pancreatic cancer (Habbe et al, 2009;Greither et al, 2010;Ryu et al, 2010), and lung cancer (Yanaihara et al, 2006;Donnem et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Monitoring microRNAs Using a Molecular Beacon in CD133⁺/CD338⁺Human Lung Adenocarcinoma-initiating A549 Cells

Yao

Sun²,

Ma³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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MicroRNA 34c Gene Down-regulation via DNA Methylation Promotes Self-renewal and Epithelial-Mesenchymal Transition in Breast Tumor-initiating Cells

Cited by 136 publications

References 44 publications

Identification of microRNA expression profile related to lymph node status in women with early-stage grade 1–2 endometrial cancer

Identification of microRNA expression profile related to lymph node status in women with early-stage grade 1–2 endometrial cancer

Downregulation of miR-129-2 by promoter hypermethylation regulates breast cancer cell proliferation and apoptosis

Monitoring microRNAs Using a Molecular Beacon in CD133⁺/CD338⁺Human Lung Adenocarcinoma-initiating A549 Cells

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MicroRNA 34c Gene Down-regulation via DNA Methylation Promotes Self-renewal and Epithelial-Mesenchymal Transition in Breast Tumor-initiating Cells

Cited by 136 publications

References 44 publications

Identification of microRNA expression profile related to lymph node status in women with early-stage grade 1–2 endometrial cancer

Identification of microRNA expression profile related to lymph node status in women with early-stage grade 1–2 endometrial cancer

Downregulation of miR-129-2 by promoter hypermethylation regulates breast cancer cell proliferation and apoptosis

Monitoring microRNAs Using a Molecular Beacon in CD133+/CD338+Human Lung Adenocarcinoma-initiating A549 Cells

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Monitoring microRNAs Using a Molecular Beacon in CD133⁺/CD338⁺Human Lung Adenocarcinoma-initiating A549 Cells