miR-340 and ZEB1 negative feedback loop regulates TGF-β- mediated breast cancer progression

Hou, Li; Yu, Yue; Xie, Ye; Wang, Jie; Mao, Jie; Zhang, Bin; Wang, Xin; Cao, Xu

doi:10.18632/oncotarget.8421

Cited by 26 publications

(34 citation statements)

References 41 publications

(40 reference statements)

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“…SNAIL1 also promotes ZEB1 expression , while its transcription is inhibited by multiple other molecules in this process such as miR‐200, miR‐340, miR‐1199, and GRHL2. ZEB1 can also inhibit the expression of these molecules as it forms double‐negative circuits with each one of them . ZEB1 and SNAIL1 also repress the expression of miR‐34 and miR‐200, respectively .…”

Section: Resultsmentioning

confidence: 99%

“…), being each phenotype defined in agreement with experimental markers. The activation of ESRP1, miR‐190, CD24, GRHL2, miR‐200, miR‐1199‐5p (referred to as miR‐1199 thereafter), miR‐340, miR‐34, and CDH1 characterize the epithelial (E) phenotype . The M phenotype corresponds to the activation of VIM, SNAIL1, ZEB1, HAS2, CD44s, and HA .…”

Section: Resultsmentioning

confidence: 99%

“…Regarding miR‐1199, Diepenbruck et al showed that in the presence of TGFβ this molecule presents similar functions to the miR‐200 family members miR‐200b‐3p and miR‐429‐3, whose overexpression destabilizes the transition to the mesenchymal state in MCF10A cells. In spite of the role played in EMT of normal breast cells (MCF10A), miR‐1199 and miR‐340 also present an important role in breast cancer cell lines: for example miR‐340 overexpression inhibits breast cancer progression in the MDA‐MB‐231 breast cancer cell line , while miR‐1199 was verified to inhibit ZEB1 in the Py2T murine breast cancer cell line . Moreover, in the presence of TGF‐β, miR‐1199 delays EMT in Py2T cells .…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, new miRNAS were also described to interact with ZEB1, such as miR‐1199‐5p, miR‐340, and miR‐190. The first and the second participate in a double‐negative feedback loop with ZEB1 that controls EMT‐mediated breast cancer progression . The third one was identified to suppress TGF‐β signaling during EMT .…”

Section: Introductionmentioning

confidence: 99%

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Dynamics of the feedback loops required for the phenotypic stabilization in the epithelial‐mesenchymal transition

Silveira

Mombach

2019

The FEBS Journal

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The epithelial‐mesenchymal transition (EMT) is a complex mechanism in which cells undergo a transition from epithelial to mesenchymal phenotypes (there is also an intermediary hybrid state) in response to microenvironmental alterations and aberrant stimuli triggered by molecules such as TGF‐β. Recent studies in breast cancer progression reported new feedback loops and new participant molecules such as microRNAs 340 and 1199. In this work, we propose a logical model of EMT contemplating the influence of these new published molecules on the regulatory core of EMT. The model results were compared with theoretical and experimental data for the human breast epithelial cell line MCF10A presenting excellent agreement. We propose that the miRNAs 340 and 1199 should be considered phenotypic stability factors of the hybrid state based on the positive feedback loops they form with ZEB1. In addition, the model allows the prediction of phenotype probabilities at the coexistence region. For the tristable dynamics when epithelial, hybrid, and mesenchymal phenotypes coexist, we found that the hybrid state is the most probable, agreeing with experiments. Our results highlight new mechanisms related to the EMT dynamics in response to TGF‐β stimulus in epithelial breast cells and might help the design of therapeutic strategies for breast cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dynamics of the feedback loops required for the phenotypic stabilization in the epithelial‐mesenchymal transition

Silveira

Mombach

2019

The FEBS Journal

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“…Whether this resistance presents in HCC requires further study. Overexpression of miR-340 was demonstrated to reduce the expression of mesenchymal phenotypic markers while increasing the expression of epithelial phenotypic markers, thereby inhibiting EMT in breast cancer cells (27). Autophagy may be observed in a number of physiological and pathological conditions, and it has been reported that miR-340 is able to repress E3 ubiquitin-protein ligase XIAP, which is an important anti-autophagy factor in tumor cells, and thereby promotes autophagy (22,28).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-340 inhibits tumor cell proliferation, migration and invasion, and induces apoptosis in hepatocellular carcinoma

Wang

Song

Huang

2017

Molecular Medicine Reports

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MicroRNAs (miRs) are short RNAs that serve a role in the origination and progression of hepatocellular carcinoma (HCC). miR‑340 has been identified to be a novel tumor suppressor. The present study investigated the antitumor function of miR‑340 in HCC. In the present study, it was detected that miR‑340 was significantly decreased in HCC cancer tissues and human HCC cell lines using reverse transcription‑quantitative polymerase chain reaction analysis. Cell Counting kit‑8 and apoptosis assays demonstrated that miR‑340 reduced cell proliferation and induced cellular apoptosis in HCC cell lines. A Transwell invasion assay demonstrated that miR‑340 suppressed the migration and invasion of HCC cell lines. In addition, S‑phase kinase‑associated protein 2 (SKP2), which may be repressed by miR‑340 in HCC cell lines, was identified to be a potential target of miR‑340. The results of the present study revealed that miR‑340 serves a tumor suppressor role by influencing the proliferation, apoptosis, migration and invasion of HCC cell lines, which may be explained by the downregulation of SKP2 by miR‑340.

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CUL4A‐mediated ZEB1/microRNA‐340‐5p/HMGB1 axis promotes the development of osteoporosis

Chen

Zheng

et al. 2023

J Biochem & Molecular Tox

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Understanding the molecular mechanisms underlying osteoclast differentiation provides insights into bone loss and even osteoporosis. The specific mechanistic actions of cullin 4A (CUL4A) in osteoclast differentiation and resultant osteoporosis is poorly explored. We developed a mouse model of osteoporosis using bilateral ovariectomy (OVX) and examined CUL4A expression. It was noted that CUL4A expression was increased in the bone marrow of OVX mice. Overexpression of CUL4A promoted osteoclast differentiation, and knockdown of CUL4A alleviated osteoporosis symptoms of OVX mice. Bioinformatic analyses were applied to identify the downstream target genes of microRNA‐340‐5p (miR‐340‐5p), followed by interaction analysis. The bone marrow macrophages (BMMs) were isolated from femur of OVX mice, which were transfected with different plasmids to alter the expression of CUL4A, Zinc finer E‐box binding homeobox 1 (ZEB1), miR‐340‐5p, and Toll‐like receptor 4 (TLR4). ChIP assay was performed to detect enrichment of ZEB1 promoter by H3K4me3 antibody in BMMs. ZEB1 was overexpressed in the bone marrow of OVX mice. Overexpression of CUL4A mediated H3K4me3 methylation to increase ZEB1 expression, thus promoting osteoclast differentiation. Meanwhile, ZEB1 could inhibit miR‐340‐5p expression and upregulate HMGB1 to induce osteoclast differentiation. Overexpressed ZEB1 activated the TLR4 pathway by regulating the miR‐340‐5p/HMGB1 axis to induce osteoclast differentiation, thus promoting the development of osteoporosis. Overall, E3 ubiquitin ligase CUL4A can upregulate ZEB1 to repress miR‐340‐5p expression, leading to HMGB1 upregulation and the TLR4 pathway activation, which promotes osteoclast differentiation and the development of osteoporosis.

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miR-340 and ZEB1 negative feedback loop regulates TGF-β- mediated breast cancer progression

Cited by 26 publications

References 41 publications

Dynamics of the feedback loops required for the phenotypic stabilization in the epithelial‐mesenchymal transition

Dynamics of the feedback loops required for the phenotypic stabilization in the epithelial‐mesenchymal transition

MicroRNA-340 inhibits tumor cell proliferation, migration and invasion, and induces apoptosis in hepatocellular carcinoma

CUL4A‐mediated ZEB1/microRNA‐340‐5p/HMGB1 axis promotes the development of osteoporosis

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