Gremlin1 promotes carcinogenesis of glioma in vitro

Guan, Yongchang; Cheng, Wen; Zou, Cunyi; Wang, Tingzhong; Cao, Zhi

doi:10.1111/1440-1681.12697

Cited by 25 publications

(26 citation statements)

References 24 publications

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“…GREM1 is overexpressed and increases cell growth and proliferation in lung adenocarcinoma [30]. Furthermore, GREM1 promotes carcinogenesis of glioma in vitro [31,32].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: LncRNA PVT1 Facilitates Tumorigenesis and Progression of Glioma via Regulation of MiR-128-3p/GREM1 Axis and BMP Signaling Pathway

Zhang

et al. 2018

Neurotherapeutics

134

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The current research was aimed at probing into the role of long noncoding RNA (lncRNA) PVT1 in the pathogenesis of glioma and the regulatory mechanism of PVT1/miR-128-3p/GREM1 network in glioma via regulation of the bone morphogenetic protein (BMP) signaling pathway. Microarray analysis was used for preliminary screening for candidate lncRNAs and mRNAs in glioma tissues. Real-time quantitative polymerase chain reaction, Western blot, MTT assay, flow cytometry, migration and invasion assays, and xenograft tumor model were utilized to examine the influence of the lncRNA PVT1/miR-128-3p/GREM1 network on the biological functions of glioma cells. Luciferase assay and RNA-binding protein immunoprecipitation assay were used to validate the miR-128-3p-target relationships with lncRNA PVT1 or GREM1. In addition, the impact of GREM1 on BMP signaling pathway downstream proteins BMP2 and BMP4 was detected via Western blot. LncRNA PVT1 was highly expressed in human glioma tissues and significantly associated with WHO grade (I-II vs III-IV; p < 0.05). There existed a regulatory relationship between lncRNA PVT1 and miR-128-3p as well as that between miR-128-3p and GREM1. MiR-128-3p was downregulated, whereas GREM1 was upregulated in glioma tissues in comparison with para-carcinoma tissues. Overexpression of GREM1 promoted the proliferation and metastatic potential of glioma cells, whereas miR-128-3p mimics inhibited the glioma cell activity through targeting GREM1. Furthermore, lncRNA PVT1 acted as a sponge of miR-128-3p and, thus, influenced the BMP signaling pathway downstream proteins BMP2 and BMP4 through regulating GREM1. LncRNA PVT1 modulated GREM1 and BMP downstream signaling proteins through sponging miR-128-3p, thereby promoting tumorigenesis and progression of glioma.

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“…GREM1 is overexpressed and increases cell growth and proliferation in lung adenocarcinoma [30]. Furthermore, GREM1 promotes carcinogenesis of glioma in vitro [31,32].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: LncRNA PVT1 Facilitates Tumorigenesis and Progression of Glioma via Regulation of MiR-128-3p/GREM1 Axis and BMP Signaling Pathway

Zhang

et al. 2018

Neurotherapeutics

134

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“…Importantly, proinflammatory genes and ECM-related genes also were elevated. Moreover, the GO enrichment analysis of these data emphasizes the role of wound healing as one of the biological processes implicated in Gremlin-mediated responses, which could be related to GREMLIN-induced phenotype transformations previously described in different cell types [7,[57][58][59][60][61]. Moreover, the ECM region and structural constituent are the main highlighted terms of cellular components and molecular function, respectively.…”

Section: Discussionmentioning

confidence: 62%

VEGFR2 Blockade Improves Renal Damage in an Experimental Model of Type 2 Diabetic Nephropathy

Lavoz

Rodrigues-Díez

Plaza

et al. 2020

JCM

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The absence of optimal treatments for Diabetic Nephropathy (DN) highlights the importance of the search for novel therapeutic targets. The vascular endothelial growth factor receptor 2 (VEGFR2) pathway is activated in experimental and human DN, but the effects of its blockade in experimental models of DN is still controversial. Here, we test the effects of a therapeutic anti-VEGFR2 treatment, using a VEGFR2 kinase inhibitor, on the progression of renal damage in the BTBR ob/ob (leptin deficiency mutation) mice. This experimental diabetic model develops histological characteristics mimicking the key features of advanced human DN. A VEGFR2 pathway-activation blockade using the VEGFR2 kinase inhibitor SU5416, starting after kidney disease development, improves renal function, glomerular damage (mesangial matrix expansion and basement membrane thickening), tubulointerstitial inflammation and tubular atrophy, compared to untreated diabetic mice. The downstream mechanisms involved in these beneficial effects of VEGFR2 blockade include gene expression restoration of podocyte markers and downregulation of renal injury biomarkers and pro-inflammatory mediators. Several ligands can activate VEGFR2, including the canonical ligands VEGFs and GREMLIN. Activation of a GREMLIN/VEGFR2 pathway, but not other ligands, is correlated with renal damage progression in BTBR ob/ob diabetic mice. RNA sequencing analysis of GREMLIN-regulated genes confirm the modulation of proinflammatory genes and related-molecular pathways. Overall, these data show that a GREMLIN/VEGFR2 pathway activation is involved in diabetic kidney disease and could potentially be a novel therapeutic target in this clinical condition.

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“…It has been reported that mesenchymal stromal cell-derived GREM1 can promote EMT in human esophageal squamous cell carcinoma [37]. Knockdown of GREM1 also inhibits EMT and invasion of glioma cells [38].…”

Section: Introductionmentioning

confidence: 98%

“…GREM1 is also involved in the fibrosis of various organs, including lung [29][30][31], kidney [32][33][34], and pancreas [35]. Interestingly, EMT phenomenon induced by GREM1 is known to be important for organ fibrosis [36] and tumor promotion [37,38]. GREM1 activates EMT process and profibrotic phenotype in tubular epithelial cells [36].…”

Section: Introductionmentioning

confidence: 99%

DHA inhibits Gremlin-1-induced epithelial-to-mesenchymal transition via ERK suppression in human breast cancer cells

et al. 2020

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Docosahexaenoic acid (DHA) is an omega-3 fatty acid abundant in fish oils. It is known to have an inhibitory effect on various diseases such as inflammation, diabetes, and cancer. Epithelial-to-mesenchymal transition (EMT) is a process that epithelial cells gain migratory property to become mesenchymal cells involved in wound healing, organ fibrosis, and cancer progression. Gremlin-1 (GREM1) is a bone morphogenetic protein antagonist known to play a role in EMT. However, the role of GREM1 in the induction of EMT in human breast cancer cells and the effect of DHA on GREM1-induced EMT remain unclear. Establishment of GREM1 knockdown cell lines was performed using lentiviral shRNAs. Expression of EMT markers was determined by qRT-PCR and Western blotting. Effect of GREM1 and/or DHA on cell migration was investigated using wound healing assay. The level of GREM1 expression in human breast cancer tissues was determined by Oncomine database mining. GREM1 induced the expression of genes including N-cadherin, vimentin, and Slug. GREM1 promoted the migration of human breast cancer cells. GREM1 enhanced the expression of phosphorylated extracellular signal-regulated kinase (p-ERK) and the ERK activation was involved in EMT. Interestingly, DHA reduced the expression of GREM1. DHA also inhibited the expression of mesenchymal cell-associated genes and cell migration induced by GREM1. Furthermore, DHA suppressed the expression of p-ERK induced by GREM1. These results indicate that GREM1-ERK axis plays a role in EMT in human breast cancer cells and DHA is a putative compound that can inhibit EMT by inhibiting GREM1 signal transduction.

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Gremlin1 promotes carcinogenesis of glioma in vitro

Cited by 25 publications

References 24 publications

RETRACTED: LncRNA PVT1 Facilitates Tumorigenesis and Progression of Glioma via Regulation of MiR-128-3p/GREM1 Axis and BMP Signaling Pathway

RETRACTED: LncRNA PVT1 Facilitates Tumorigenesis and Progression of Glioma via Regulation of MiR-128-3p/GREM1 Axis and BMP Signaling Pathway

VEGFR2 Blockade Improves Renal Damage in an Experimental Model of Type 2 Diabetic Nephropathy

DHA inhibits Gremlin-1-induced epithelial-to-mesenchymal transition via ERK suppression in human breast cancer cells

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