WIF1 re-expression in glioblastoma inhibits migration through attenuation of non-canonical WNT signaling by downregulating the lncRNA MALAT1

Vassallo, Irene; Zinn, Pascal O.; Lai, Maode; Rajakannu, P; Mf, Hamou; Hegi, Monika E.

doi:10.1038/onc.2015.61

Cited by 127 publications

(119 citation statements)

References 58 publications

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“…Findings on Wnt5a roles and functions in these tumors are restricted to the observed increased motility in cultured cell lines (25,27). Recently, however, it has been shown that the enhanced migration caused in hGBMs by reduced Wnt inhibitor 1 activity is mediated by Wnt5a (48). We now demonstrated that Wnt5a functions as a master regulator in determining the prototypical invasive glioma potential in hGBMs, particularly, in their TPCs.…”

Section: Discussionmentioning

confidence: 83%

Wnt5a Drives an Invasive Phenotype in Human Glioblastoma Stem-like Cells

et al. 2017

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Brain invasion by glioblastoma determines prognosis, recurrence, and lethality in patients, but no master factor coordinating the invasive properties of glioblastoma has been identified. Here we report evidence favoring such a role for the noncanonical WNT family member Wnt5a. We found the most invasive gliomas to be characterized by Wnt5a overexpression, which correlated with poor prognosis and also discriminated infiltrating mesenchymal glioblastoma from poorly motile proneural and classical glioblastoma. Indeed, Wnt5a overexpression associated with tumor-promoting stem-like characteristics (TPC) in defining the character of highly infiltrating mesenchymal glioblastoma cells (Wnt5a High ). Inhibiting Wnt5a in mesenchymal glioblastoma TPC suppressed their infiltrating capability. Conversely, enforcing high levels of Wnt5a activated an infiltrative, mesenchymal-like program in classical glioblastoma TPC and Wnt5aLow mesenchymal TPC. In intracranial mouse xenograft models of glioblastoma, inhibiting Wnt5a activity blocked brain invasion and increased host survival. Overall, our results highlight Wnt5a as a master regulator of brain invasion, specifically TPC, and they provide a therapeutic rationale to target it in patients with glioblastoma. Cancer Res; 77(4); 996-1007. Ó2016 AACR.

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Section: Discussionmentioning

confidence: 83%

Wnt5a Drives an Invasive Phenotype in Human Glioblastoma Stem-like Cells

et al. 2017

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“…Up-regulation of MALAT1 facilitates cell proliferation, migration, and invasion in lung cancer, glioblastoma, esophageal squamous cell carcinoma, renal cell carcinoma, colorectal cancer, osteosarcoma, multiple myeloma, gastric cancer, gallbladder cancer. [10][11][12][13][14][15][16][17][18][19][20] In addition, MALAT1 is associated with the malignant status and poor prognosis in glioma and clear cell renal cell carcinoma. 21,22 Finally, the high level of MALAT1 can act as a marker to predict disease progression in colorectal cancer, multiple myeloma, pancreatic cancer, and non-small cell lung cancer.…”

Section: Introductionmentioning

confidence: 99%

MALAT1 functions as a competing endogenous RNA to mediate Rac1 expression by sequestering miR-101b in liver fibrosis

Cai

et al. 2015

Cell Cycle

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Abbreviations: a-SMA, smooth muscle a-actin; Ad-shCtrl, adenoviral vectors expressing the scrambled shRNA; Ad-shMALAT1, adenoviral vectors expressing shRNA against MALAT1. EdU, 5-Ethyny-2 0 -deoxyuridine; Ago2, Argonaute-2; BDL, bile duct ligation; CCl 4 , carbon tetrachloride; ceRNAs, competing endogenous RNAs; Col1a1, collagen type I, a 1; DMEM, Dulbecco's modified Eagle's medium; HSCs, hepatic stellate cells; IgG, immunoglobulin G; IHC, immunohistochemical; lncRNAs, long noncoding RNAs; MALAT1, Metastasis-associated lung adenocarcinoma transcript 1; miR-101, microRNA-101; miR-NC, miR-101b negative control; miRNAs, microRNAs; ncRNAs, non-coding RNAs; qRT-PCR, quantitative real-time PCR; Rac1, RAS-related C3 botulinum substrate 1; siCtrl, scrambled siRNA; siRNAs, small interfering RNAs.Emerging evidence shows that Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a pivotal role in cell proliferation, migration, and invasion in tumors. However, the biological role and underlying mechanism of MALAT1 in liver fibrosis remains undefined. In this study, up-regulation of MALAT1 was observed in fibrotic liver tissues and in activated hepatic stellate cells (HSCs). In addition, depletion of MALAT1 inhibited the activation of HSCs in vitro and attenuated collagen deposits in vivo. Our results demonstrated that MALAT1 expression is negatively correlated with microRNA-101b (miR-101b) expression. Furthermore, there was a negative feedback loop between the levels of MALAT1 and miR-101b. Luciferase reporter assay indicated that MALAT1 and RAS-related C3 botulinum substrate 1 (Rac1) are targets of miR-101b. We uncovered that MALAT1 regulates Rac1 expression through miR-101b as a competing endogenous RNA (ceRNA), thereby influencing the proliferation, cell cycle and activation of primary HSCs. Collectively, The ceRNA regulatory network may prompt a better understanding of liver fibrogenesis and contribute to a novel therapeutic strategy for liver fibrosis.

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“…In 2012, our laboratory used ChIP-seq assay of TCF4 and STAT3 and data mining of patient cohorts to derive the molecular subtypes of GBM (42). Moreover, the lncRNA MALAT1 has been reported to be regulated in non-canonical WNT/Ca 2þ / signaling (43). In this study, we disclosed that a high level of NEAT1 negatively regulated WNT negative signaling regulation factors (Axin2, ICAT, and GS3KB).…”

Section: Discussionmentioning

confidence: 76%

Long Noncoding RNA NEAT1, Regulated by the EGFR Pathway, Contributes to Glioblastoma Progression Through the WNT/β-Catenin Pathway by Scaffolding EZH2

Chen

Cai

Wang³

et al. 2018

Clinical Cancer Research

291

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Purpose: Long noncoding RNAs have been implicated in gliomagenesis, but their mechanisms of action are mainly undocumented. Through public glioma mRNA expression data sets, we found that NEAT1 was a potential oncogene. We systematically analyzed the clinical significance and mechanism of NEAT1 in glioblastoma.Experimental Design: Initially, we evaluated whether NEAT1 expression levels could be regulated by EGFR pathway activity. We subsequently evaluated the effect of NEAT1 on the WNT/ b-catenin pathway and its target binding gene. The animal model supported the experimental findings.Results: We found that NEAT1 levels were regulated by EGFR pathway activity, which was mediated by STAT3 and NFkB (p65) downstream of the EGFR pathway. Moreover, we found that NEAT1 was critical for glioma cell growth and invasion by increasing b-catenin nuclear transport and downregulating ICAT, GSK3B, and Axin2. Taken together, we found that NEAT1 could bind to EZH2 and mediate the trimethylation of H3K27 in their promoters. NEAT1 depletion also inhibited GBM cell growth and invasion in the intracranial animal model.Conclusions: The EGFR/NEAT1/EZH2/b-catenin axis serves as a critical effector of tumorigenesis and progression, suggesting new therapeutic directions in glioblastoma. Clin Cancer Res; 1-12.Ó2017 AACR.

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WIF1 re-expression in glioblastoma inhibits migration through attenuation of non-canonical WNT signaling by downregulating the lncRNA MALAT1

Cited by 127 publications

References 58 publications

Wnt5a Drives an Invasive Phenotype in Human Glioblastoma Stem-like Cells

Wnt5a Drives an Invasive Phenotype in Human Glioblastoma Stem-like Cells

MALAT1 functions as a competing endogenous RNA to mediate Rac1 expression by sequestering miR-101b in liver fibrosis

Long Noncoding RNA NEAT1, Regulated by the EGFR Pathway, Contributes to Glioblastoma Progression Through the WNT/β-Catenin Pathway by Scaffolding EZH2

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