Demethylation of the<i>MIR145</i>promoter suppresses migration and invasion in breast cancer

Liu, Shui Yi; Li, Xiao Yi; Chen, Wei Qun; Hu, Hui; Luo, Bo; Shi, Yu; Wu, Tang Wei; Li, Yong; Kong, Q; Lu, Hongcheng; Zhong, Lipeng

doi:10.18632/oncotarget.18686

Cited by 20 publications

(16 citation statements)

References 39 publications

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“…MicroRNAs play critical roles in atherosclerosis [52]. A microRNA, miR-145, is expressed at extraordinarily high levels in aorta and other smooth muscle-rich tissues (Supplementary Table 1) and targets ANGPT2 , among other genes, in breast cancer cells [53,54] and in brain microvascular endothelial cells [55]. We found many statistically significant atherosclerosis-associated hypermethylated DMRs near miR-145-encoding sequences in aorta (Figure 5C); however, the coordinates of the gene encoding this miRNA are uncertain.…”

Section: Resultsmentioning

confidence: 99%

“…These atherosclerosis-linked hypermethylated DMRs are located in enhancer chromatin regions that were hypomethylated in normal aorta relative to other normal tissues (Figure 5C & D). There was no evidence for atherosclerosis-linked DNA hypermethylation in the putative MIR145 promoter region (green arrow, Figure 5G) described in many studies of cancer-associated ‘promoter’ methylation of MIR145 often coupled with lower levels of miR-145 [53,57,58]. This putative promoter region extends from −1.4 kb to the beginning of the miR-145-encoding sequences and was shown to drive expression of a reporter gene in transfection experiments [59].…”

Section: Resultsmentioning

confidence: 99%

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Tissue-specific epigenetics of atherosclerosis-related ANGPT and ANGPTL genes

2019

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Aim: To understand tissue-specific regulation of angiopoietin/angiopoietin-like ( ANGPT/ANGPTL ) genes (especially the five genes embedded in introns of host genes) and their association with atherosclerosis. Methods: Transcription and epigenomic databases from various normal tissues were examined in the vicinity of ANGPT1, ANGPT2, ANGPTL1, ANGPTL2, ANGPTL3, ANGPTL4 and ANGPTL8 . Results: We identified tissue-specific enhancer chromatin regions that are likely to regulate transcription of ANGPT/ANGPTL genes and were intragenic, intergenic or host gene-linked. In addition, we found atherosclerosis-linked differentially methylated regions associated with ANGPT2 and with sequences encoding miR-145, a microRNA that targets ANGPT2 mRNA in cancers. Conclusion: Our findings implicate enhancers as major contributors to tissue-specific expression of ANGPT/ANGPTL genes, which play critical roles in angiogenesis, atherosclerosis, cancer, and inflammatory and metabolic diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Tissue-specific epigenetics of atherosclerosis-related ANGPT and ANGPTL genes

2019

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“…The underlying mechanisms of miR-145 in BRCA processes have increasingly been explored in previous studies. Liu et al revealed that the reduced expression of miR-145 in BRCA was attributed to DNA methylation and demonstrated that miR-145 repressed cell migration and invasion by targeting ANGPT2 both in vivo and in vitro [26]. Zhao et al identified that miR-145 suppressed BRCA cell migration by targeting FSCN-1 and blocked the epithelial-mesenchymal transition [27].…”

Section: Discussionmentioning

confidence: 99%

The Dysregulated Expression of KCNQ1OT1 and Its Interaction with Downstream Factors miR-145/CCNE2 in Breast Cancer Cells

Feng

Wang

Liang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Next-generation sequencing (NGS) has revealed abundant long noncoding RNAs (lncRNAs) that have been characterized as critical components of cancer biology in humans. The present study aims to investigate the role of the lncRNA KCNQ1OT1 in breast cancer (BRCA) as well as the underlying molecular mechanisms and functions of KCNQ1OT1 involved in the progression of BRCA. Methods: The Cancer Genome Atlas (TCGA) and StarBase v2.0 were used to obtain the required gene data. Dual luciferase reporter gene assays were conducted to verify the relevant intermolecular target relationships. QRT-PCR and Western blot were performed to measure the expression levels of different molecules. Cell proliferation was detected by using the MTT and colony formation assays, while cell migration and invasion were examined by transwell assay. Variations in cell apoptosis and cell cycle were determined through flow cytometry. A tumor xenograft model was applied to assess tumor growth in vivo. Results: KCNQ1OT1 was found to be remarkably highly expressed in BRCA tissues and cells. KCNQ1OT1 modulated CCNE2 through sponging miR-145 in BRCA. KCNQ1OT1 promoted tumor growth in vivo by regulating miR-145/CCNE2. Conclusion: The KCNQ1OT1/miR-145/CCNE2 axis plays a critical regulatory role in BRCA, potentially giving rise to BRCA tumorigenesis and progression. These findings provide valuable evidence for improving the diagnosis and treatment of BRCA in the future.

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“…MicroRNAs (miRNAs) are non-coding, single-stranded RNA molecules that regulate target gene expression via posttranscriptional processing [4, 5]. Recently, several studies indicated the promising role of miRNA in the diagnose and outcome prediction in several cancers [6–12].…”

Section: Introductionmentioning

confidence: 99%

microRNA-21 promotes breast cancer proliferation and metastasis by targeting LZTFL1

et al. 2019

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Background Breast cancer is the most common cancer type in female. As microRNAs play vital role in breast cancer, this study aimed to explore the molecular mechanism and clinical value of miR-21 in breast cancer. Methods qRT-PCR was performed to detect miR-21 levels in plasma of 127 healthy controls, 82 benign breast tumor, 252 breast cancer patients, as well as in breast cancer cell lines. Transwell and wound healing assay were used to analyze breast cancer metastasis in response to miR-21 inhibitor. Colony formation and eFluor™ 670 based flow cytometric analysis were used to test breast cancer proliferation following miR-21 inhibitor treatment. Leucine zipper transcription factor-like 1 (LZTFL1), the target gene of miR-21 was predicted by MIRDB, TargetScan 5.1, PicTar and miRanda. Survival analysis of LZTFL1 levels in breast cancer prognosis was estimated with the Kaplan–Meier method by log-rank test according to data from the Cancer Genome Atlas. Luciferase activity assay was performed to confirm the regulation of miR-21 on LZTFL1. LZTFL1 siRNA and miR-21 inhibitor were co-transfected to breast cancer cells, then cell proliferation, migration and epithelial–mesenchymal transition (EMT) makers were tested. BALB/c nude mice were injected in situ with Hs578T cells stably overexpressing miR-21. Breast tumor growth, metastasis and the expression of EMT markers or LZTFL1 were detected in vivo. Results Plasma miR-21 levels were elevated in breast cancer patients compared with healthy controls and benign breast tumor patients, and the miR-21 levels were significantly decreased after surgery comparing with pre operation in 44 patients. Inhibition of miR-21 suppressed cell proliferation and metastasis in breast cancer cells. LZTFL1 was identified as a novel target gene of miR-21. Knockdown of LZTFL1 overcame the suppression of miR-21 inhibitor on cell proliferation, metastasis and the expression of EMT markers in breast cancer cells. miR-21 overexpression promoted breast cancer cell proliferation and metastasis in vivo. Conclusions These results indicate that plasma miR-21 level is a crucial biomarker for breast cancer diagnosis and targeting miR-21–LZTFL1–EMT axis might be a promising strategy in breast cancer therapy. Trial registration Retrospectively registered. Electronic supplementary material The online version of this article (10.1186/s12885-019-5951-3) contains supplementary material, which is available to authorized users.

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Demethylation of theMIR145promoter suppresses migration and invasion in breast cancer

Cited by 20 publications

References 39 publications

Tissue-specific epigenetics of atherosclerosis-related ANGPT and ANGPTL genes

Tissue-specific epigenetics of atherosclerosis-related ANGPT and ANGPTL genes

The Dysregulated Expression of KCNQ1OT1 and Its Interaction with Downstream Factors miR-145/CCNE2 in Breast Cancer Cells

microRNA-21 promotes breast cancer proliferation and metastasis by targeting LZTFL1

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