Zinc finger E-box-binding homeobox 2 (ZEB2) regulated by miR-200b contributes to multi-drug resistance of small cell lung cancer

Fang, Shun; Zeng, Xiang‐Ping; Zhu, Wei; Tang, Ruixiang; Chao, Yilan; Guo, Linlang

doi:10.1016/j.yexmp.2014.04.008

Cited by 46 publications

(31 citation statements)

References 30 publications

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“…54 ZEB2 is also involved in multi-drug resistance in small cell lung cancer and cisplatin resistance in ovarian cancer. 55, 56 Consistent with these results, we found that miR-218 sensitized cells to cisplatin treatment through inhibition of Slug and ZEB2. This finding reveals a new role of miR-218/Slug/ZEB2 pathway in EMT-related drug resistance, and provides a clue to use miR-218 mimic in cancer treatment.…”

Section: Discussionsupporting

confidence: 87%

Downregulation of miR-218 contributes to epithelial–mesenchymal transition and tumor metastasis in lung cancer by targeting Slug/ZEB2 signaling

et al. 2017

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Epithelial–mesenchymal transition (EMT) has been recognized as a key element of cell migration and invasion in lung cancer; however, the underlying mechanisms are not fully elucidated. Recently, emerging evidence suggest that miRNAs have crucial roles in control of EMT and EMT-associated traits such as migration, invasion and chemoresistance. Here, we found that miR-218 expression levels were significantly downregulated in lung cancer tissues compared with adjacent non-cancerous tissues, and the levels of miR-218 were significantly associated with histological grades and lymph node metastasis. Overexpression of miR-218 inhibited cell migration and invasion as well as the EMT process. Of particular importance, miR-218 was involved in the metastatic process of lung cancer cells in vivo by suppressing local invasion and distant colonization. We identified Slug and ZEB2 as direct functional targets of miR-218. Inverse correlations were observed between miR-218 levels and Slug/ZEB2 levels in cancer tissue samples. In addition, overexpression of miR-218 in H1299 increased chemosensitivity of cells to cisplatin treatment through suppression of Slug and ZEB2. These findings highlight an important role of miR-218 in the regulation of EMT-related traits and metastasis of lung cancer in part by modulation of Slug/ZEB2 signaling, and provide a potential therapeutic strategy by targeting miR-218 in NSCLC.

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Section: Discussionsupporting

confidence: 87%

Downregulation of miR-218 contributes to epithelial–mesenchymal transition and tumor metastasis in lung cancer by targeting Slug/ZEB2 signaling

et al. 2017

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“…miR-200b suppresses arsenic-transformed cell migration by targeting protein kinase Cα, the Wnt5b-protein kinase Cα positive feedback loop and inhibiting Rac1 activation (16). miR-200b was downregulated in the adriamycin-resistant small lung cancer H69AR cells and enforced expression of miR-200b by miRNA mimics increased cell sensitivity to adriamycin (17). A previous study demonstrated that miR-200b may be a novel and valuable marker for predicting the clinical outcome of patients with glioma (18).…”

Section: Discussionmentioning

confidence: 99%

miR-200b inhibits CD133+ glioma cells by targeting the AKT pathway

Liu

Peng

et al. 2017

Oncology Letters

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MicroRNA-200b (miR-200b) is a tumor suppressor in multiple tumor types, including gastric cancer, breast cancer, ovarian cancer and glioma. The biological significance of a known normal and cancer stem cell marker, CD133, remains elusive. The aim of the present study was to identify the function and mechinism of miR-200b in suppressing CD133+ glioma cells. CD133+ glioma cells were sorted by flow cytometry. The expression of miR-200b, Ki67, GAP43, GFAP and CD133 were tested by reverse transcription-quantitative polymerase chain reaction. The binding of miR-200b to prominin 1 (PROM1) was certificated by luciferase reporter assay. Cell proliferation was analyzed by bromodeoxyuridine staining. The protein level of CD133, p-AKT, AKT and Notch1 was detected by western blot analysis. Analysis of glioma samples revealed that CD133 expression is negatively associated with miR-200b. PROM1, which is the gene that codes CD133, was certified to be a target of miR-200b. miR-200b expression inhibited the stemness properties and division of the CD133+ glioma cells. Our results identified a miR-200b/CD133/PI3K/Akt signaling axis, exploring the fundamental role of miR-200b and CD133 in glioma stem cell behavior.

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“…In a previous study, ZEB2 was found to inhibit squamous transdifferentiation of Lkb1-deficient lung adenocarcinoma by repressing DNp63 through YAP [10] and stimulate immature T-cell lymphoblastic leukemia development via enhanced tumor-initiating potential and IL-7 receptor signaling [11]. In addition, ZEB2 modulated by miR-200b or TMPRSS was associated with EMT and multidrug resistance in lung cancer [12,13]. Despite these implications, direct evidence of ZEB2 modulating chemotherapy resistance has not been demonstrated.…”

Section: Introductionmentioning

confidence: 96%

Direct interaction between miR-203 and ZEB2 suppresses epithelial–mesenchymal transition signaling and reduces lung adenocarcinoma chemoresistance

Duan¹,

Fu²,

Gao³

et al. 2016

ABBS

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miR-203 is a tumor suppressor which participates in the pathogenesis of many tumors including lung adenocarcinoma. However, the role of miR-203 in suppressing chemotherapy resistance to cisplatin (cis-diamminedichloroplatinum; DDP) as well as its molecular mechanism is still to be determined in lung adenocarcinoma. In this study, we found that miR-203 decreased lung cancer cell migration and invasion, and that increased miR-203 expression sensitized lung adenocarcinoma cells to DDP in vitro. Furthermore, ZEB2 was found to be a direct target of miR-203, which induces epithelial-mesenchymal transition (EMT) signal. Knock-down of ZEB2 significantly increased DDP chemosensitivity in lung adenocarcinoma. More interestingly, we also demonstrated that ZEB2 could directly bind to E-box of the miR-203 promoter and suppress its expression in lung adenocarcinoma. Our data reveal that miR-203 serves as a negative feedback by directly suppressing the upstream ZEB2 gene, which inhibits EMT signaling and reduces chemoresistance of DDP. Together, these results highlight a feedback loop between miR-203 and ZEB2, which participates in the pathogenesis of lung adenocarcinoma.

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Zinc finger E-box-binding homeobox 2 (ZEB2) regulated by miR-200b contributes to multi-drug resistance of small cell lung cancer

Cited by 46 publications

References 30 publications

Downregulation of miR-218 contributes to epithelial–mesenchymal transition and tumor metastasis in lung cancer by targeting Slug/ZEB2 signaling

Downregulation of miR-218 contributes to epithelial–mesenchymal transition and tumor metastasis in lung cancer by targeting Slug/ZEB2 signaling

miR-200b inhibits CD133+ glioma cells by targeting the AKT pathway

Direct interaction between miR-203 and ZEB2 suppresses epithelial–mesenchymal transition signaling and reduces lung adenocarcinoma chemoresistance

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Zinc finger E-box-binding homeobox 2 (ZEB2) regulated by miR-200b contributes to multi-drug resistance of small cell lung cancer

Cited by 46 publications

References 30 publications

Downregulation of miR-218 contributes to epithelial–mesenchymal transition and tumor metastasis in lung cancer by targeting Slug/ZEB2 signaling

Downregulation of miR-218 contributes to epithelial–mesenchymal transition and tumor metastasis in lung cancer by targeting Slug/ZEB2 signaling

miR-200b inhibits CD133+ glioma cells by targeting the AKT pathway

Direct interaction between miR-203 and ZEB2 suppresses epithelial&ndash;mesenchymal transition signaling and reduces lung adenocarcinoma chemoresistance

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Direct interaction between miR-203 and ZEB2 suppresses epithelial–mesenchymal transition signaling and reduces lung adenocarcinoma chemoresistance