MRTF-A-miR-206-WDR1 form feedback loop to regulate breast cancer cell migration

Yuan, Xiang; Liao, Xing–Hua; Yao, Ao; Qin, Huan; Fan, Lijuan; Li, Jiapeng; Hu, Peng; Li, Hui; Guo, Wei; Li, Junyan; Gu, Cheng; Bao, Lidao; Zhang, Tongcun

doi:10.1016/j.yexcr.2017.08.023

Cited by 27 publications

(18 citation statements)

References 54 publications

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“…The result of wound MiR-206 affects muscle development as a skeletal muscle-specific miRNA. 37 The elevated expression of miR-206 had been shown to inhibit the growth of gastric cancer, 38 breast cancer, 39 colorectal cancer, 40 hepatocellular carcinoma, 41 and cervical cancer. 42 Furthermore, our finding indicated that miR-206 in PCa was down-regulated which was consistent with previous researches of miR-206 in PCa, 31 which suggests that miR-206 could be the potential molecular biomarker for diagnosis of PCa.…”

Section: Mir-206 Played An Important Role Through Regulating Cxcl11mentioning

confidence: 99%

MiR‐206 inhibits proliferation and migration of prostate cancer cells by targeting CXCL11

Wang

Hui

et al. 2018

The Prostate

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Section: Mir-206 Played An Important Role Through Regulating Cxcl11mentioning

confidence: 99%

MiR‐206 inhibits proliferation and migration of prostate cancer cells by targeting CXCL11

Wang

Hui

et al. 2018

The Prostate

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“…In addition, VWCE promotes tumor cell migration and invasion through EMT, as VWCE overexpression leads to decreased levels of Ncadherin, vimentin, and the EMT-induced transcription factor, ZEB1, as well as elevated E-cadherin levels, indicating a significant inhibition of EMT processes. WDR1 enhances the effect of MRTF-A-induced breast cancer cell migration by promoting the expression of EMT markers and migration markers by RhoA-MRTF (34). WDR1-mediated actin dynamics are required for membrane-associated adhesive junction remodeling in tumor cells.…”

Section: Discussionmentioning

confidence: 98%

VWCE Functions as a Tumor Suppressor in Breast Cancer Cells

et al. 2020

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Breast cancer remains a leading cause of cancer-related death, for which the majority of deaths result from metastases. Von Willebrand factor C and EGF domain (VWCE) is a member of the Von Willebrand factor (VWF) gene family; however, its function, regulatory mechanism, and clinical value in breast cancer remain unclear. In the present study, we sought to elucidate the role of VWCE in breast cancer metastasis. We examined the expression of VWCE in breast cancer tissues and normal control tissues of 50 breast cancer patients. We found that VWCE expression was downregulated in breast cancer cells and tissues compared to normal breast epithelial cells or the adjacent normal tissues. To explore the role of VWCE in human breast cancer development, we introduced a VWCE-overexpressing or control lentiviral vector into the breast cancer MDA-MB-453 and MDA-MB-231 lines in vitro. The overexpression of VWCE inhibited the proliferation, migration, invasion, and chemoresistance of the breast cancer cell lines. More importantly, the forced expression of VWCE suppressed tumor formation and metastasis in nude mice. iTRAQ-based quantitative proteomic analysis revealed that VWCE overexpression induced a 10-fold decrease in the level of WD-repeat domain 1 (WDR1) protein expression. Rescue experiments further verified that WDR1 was a downstream molecule of VWCE, and WDR1 overexpression reversed the above effects of VWCE overexpression on tumor growth. Therefore, VWCE may represent a novel tumor suppressor, for which its deregulation promotes breast cancer progression via the upregulation of WDR1.

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“…On the other hand, as con rmed by luciferase reporter assay, our data also suggested that methylationmediated silencing of miR-1250-5p could result in upregulation of another direct target, WDR1. WDR1 was found to be upregulated and associated with poor prognosis in breast and lung cancer [41][42][43]. In lung cancer cells, the oncogenic function of WDR1 in the regulation of cellular proliferation was shown to be mediated by dephosphorylation and hence increased nuclear translocation of YAP protein, a downstream effector for Hippo signaling pathway, hence activation of the transcription of proproliferative genes, such as cyclin A2, cyclin B1, cyclin D1, cyclin E and Cdk1 [41].…”

Section: Discussionmentioning

confidence: 99%

“…In lung cancer cells, the oncogenic function of WDR1 in the regulation of cellular proliferation was shown to be mediated by dephosphorylation and hence increased nuclear translocation of YAP protein, a downstream effector for Hippo signaling pathway, hence activation of the transcription of proproliferative genes, such as cyclin A2, cyclin B1, cyclin D1, cyclin E and Cdk1 [41]. Moreover, in breast cancer cells, knockdown of WDR1 resulted in inhibition of cancer cell migration and invasion [42,43]. By contrast, in the absence of SDF-1, the inhibitory effect of cell migration by knockdown of WDR1 was weakened, con rming the oncogenic property of WDR1 in the promotion of SDF-1-dependent migration of lymphoma cell [28].…”

Section: Discussionmentioning

confidence: 99%

miR-1250-5p is a novel tumor suppressive intronic miRNA hypermethylated in non-Hodgkin’s lymphoma: novel targets with impact on ERK signaling and cell migration

Zhang

Wang

Chim

2020

Preprint

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Background miR-1250 is localised to the second intron of AATK at chromosome 17q25. As a CpG island is present at the putative promoter region of its host gene, AATK, we postulated that the intronic miR-1250-5p is a tumor suppressor miRNA co-regulated with its host gene, AATK, by promoter DNA methylation in non-Hodgkin’s lymphoma (NHL). Methods AATK/miR-1250 methylation was studied in healthy controls, including ten normal peripheral blood buffy coat and eleven normal tonsils, ten lymphoma cell lines, and 120 primary lymphoma samples by methylation-specific PCR (MSP). The expression of miR-1250-5p and AATK was investigated by quantitative real-time PCR. Tumor suppressor properties of miR-1250-5p were demonstrated by over-expression of precursor miR-1250-5p in lymphoma cells. The target of miR-1250-5p was verified by luciferase reporter assay. Results AATK/miR-1250 methylation was absent in healthy peripheral blood and tonsils, but detected in five (50%) NHL cell lines. AATK/miR-1250 methylation correlated with repression of miR-1250-5p and AATK in NHL cell lines. In completely methylated SU-DHL-6 and SUP-T1 cells, treatment with 5-AzadC led to promoter demethylation and re-expression of both miR-1250-5p and AATK. In primary lymphoma samples, AATK/miR-1250 was frequently methylated in B-cell lymphoma (n = 41, 44.09%) and T-cell lymphoma (n = 9, 33.33%) with a comparable frequency (P = 0.318). In SU-DHL-1 cells, restoration of miR-1250-5p resulted in decreased cellular proliferation by MTS assay, increased cell death by trypan blue staining and enhanced apoptosis by annexin V-PI assay. Moreover, MAPK1 and WDR1 were verified as direct targets of miR-1250-5p by luciferase assay. In 39 primary NHLs, miR-1250-5p expression was shown to be inversely correlated with each of MAPK1 (P = 0.05) and WDR1 (P = 0.031) by qRT-PCR. Finally, in SU-DHL-1 cells, overexpression of miR-1250-5p led to repression of MAPK1 and WDR1 at both transcript and protein levels, with downregulation of phospho-ERK2 by Western-blotting and inhibition of SDF-1-dependent cell migration by transwell assay. Conclusions miR-1250-5p is a novel tumor suppressive intronic miRNA co-regulated and silenced by promoter DNA methylation of its host gene AATK in NHL. MAPK1 and WDR1 are novel miR-1250-5p direct targets rendering inhibition of MAPK/ERK signaling and SDF-1-dependent cell migration, hence implicated in survival and dissemination of lymphoma.

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MRTF-A-miR-206-WDR1 form feedback loop to regulate breast cancer cell migration

Cited by 27 publications

References 54 publications

MiR‐206 inhibits proliferation and migration of prostate cancer cells by targeting CXCL11

MiR‐206 inhibits proliferation and migration of prostate cancer cells by targeting CXCL11

VWCE Functions as a Tumor Suppressor in Breast Cancer Cells

miR-1250-5p is a novel tumor suppressive intronic miRNA hypermethylated in non-Hodgkin’s lymphoma: novel targets with impact on ERK signaling and cell migration

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