miR-375 regulates the canonical Wnt pathway through FZD8 silencing in arthritis synovial fibroblasts

Miao, Chenggui; Wei-jing, Shi; Xiong, Youyi; Yu, Hao; Zhang, Xiaolin; Qin, Meisong; Du, Cheng; Song, Tong-wen; Li, Jun

doi:10.1016/j.imlet.2015.01.003

Cited by 46 publications

(31 citation statements)

References 40 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Analyzing MAML3 fusion-positive tumors by pathway analysis, we found that genes in developmental pathways, Wnt receptor signaling and Hedgehog signaling, were significantly overexpressed (Figure S3D and Figure 4B), several of which were also hypomethylated (Figure S3C). By miRNA analysis, the strongest marker of the fusion-positive tumors was an underexpression of miR-375, a negative regulator of Wnt signaling pathway member FZD8 (Miao et al, 2015) (Figure S3E and Figure 4B). Finally, RPPA analysis showed Wnt pathway members β-catenin, DVL3, and GSK3 were overexpressed in MAML3 fusion-positive tumors (Figure 4B).…”

Section: Resultsmentioning

confidence: 99%

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

Fishbein¹,

Leshchiner²,

Walter³

et al. 2017

Cancer Cell

552

741

View full text Add to dashboard Cite

Summary We report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCC/PGLs), a rare tumor type. Multi-platform integration revealed that PCC/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically-mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, NF1). We also discovered fusion genes in PCC/PGL, involving MAML3, BRAF, NGFR and NF1. Integrated analysis classified PCC/PGLs into four molecularly-defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCC/PGL included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine.

show abstract

Section: Resultsmentioning

confidence: 99%

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

Fishbein¹,

Leshchiner²,

Walter³

et al. 2017

Cancer Cell

552

741

View full text Add to dashboard Cite

show abstract

“…These genes have either been previously implicated in arthritis or terminal differentiation of chondrocytes. For example, serum FABP4 was increased in patients with rheumatoid arthritis and metabolic syndrome [53, 54]; DLX2 promoted osteogenic differentiation of stem cells and enhanced mineralization [55]; POSTN induced the expression of IL-6, IL-8, and MMPs [56]; APCDD1 was associated with increased expression of RunX2 and elevated alkaline phosphatase activity [57]; NDP activated Wnt/β-catenin pathway associated with OA [58, 59]; SOX-4 signaling resulted in repression of SOX-9, a master transcription factor critical for chondrogenesis [60]; Silence of FZD8 resulted in decreased expression of MMP-3 [61]. The downregulation of the expression of these genes by PC was consistent with its OA disease-modifying activity.…”

Section: Discussionmentioning

confidence: 99%

Biological Effects of Phosphocitrate on Osteoarthritic Articular Chondrocytes

Sun

Franklin

Mauerhan

et al. 2017

TORJ

View full text Add to dashboard Cite

Background:Phosphocitrate (PC) inhibits osteoarthritis (OA) in Hartley guinea pigs. However, the underlying molecular mechanisms remain poorly understood.Objective:This study sought to examine the biological effect of PC on OA chondrocytes and test the hypothesis that PC may exert its OA disease modifying effect, in part, by inhibiting the expression of genes implicated in OA disease process and stimulating the production of extracellular matrices.Method:OA chondrocytes were cultured in the absence or presence of PC. Total RNA was extracted and subjected to microarray analyses. The effect of PC on proliferation and chondrocyte-mediated calcification were examined in monolayer culture. The effect of PC on the production of extracellular matrices was examined in micromass culture.Results:PC downregulated the expression of numerous genes classified in proliferation and apoptosis while upregulating the expression of many genes classified in transforming growth factor-β (TGF-β) receptor signaling pathway and ossification. PC also downregulated the expressions of many genes classified in inflammatory response and Wnt receptor signaling pathways. Consistent with its effect on the expression of genes classified in proliferation, ossification, and skeletal development, PC inhibited the proliferation of OA chondrocytes and chondrocyte-mediated calcification while stimulating the production of extracellular matrices.Conclusion:PC may exert its OA disease modifying effect, in part, through a crystal-independent mechanism or by inhibiting the expressions of many genes implicated in OA disease process, and at the same time, stimulating the expression of genes implicated in chondroprotection and production of extracellular matrices.

show abstract

“…Wnt/β-catenin signaling is initiated when Wnt ligands bind to FZD members, including FZD8[47]. For example, FZD8 has been shown to regulate the canonical Wnt/β-catenin pathway in arthritis synovial fibroblasts and alveolar epithelial cell trans-differentiation in rat models [48, 49]. Moreover, FZD8-mediated Wnt/β-catenin signaling appeared to participate in mediating resistance to chemotherapy in triple-negative breast cancer [50].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-375 suppresses human colorectal cancer metastasis by targeting Frizzled 8

Wen

Liu

et al. 2016

Oncotarget

View full text Add to dashboard Cite

microRNAs are aberrantly expressed during the development and progression of a variety of human cancers, including colorectal cancer (CRC). Of these microRNAs, microRNA-375 (miR-375) was previously observed to be downregulated in human colorectal cancer(CRC) plasma and tissues, but its functions are largely unknown. Here, we investigated the impact of miR-375 on CRC metastasis. Specifically, miR-375 expression was significantly decreased in human CRC tissues compared with their matched noncancerous tissues (NCTs), and low levels of miR-375 predicted tumor metastatic potential. The up-regulation of miR-375 suppressed colorectal cancer cell migration and invasion in vitro and reduced tumor metastases in murine models established by both orthotopic implantation and spleen injection. Furthermore, we identified Frizzled 8 (FZD8) as a direct target of miR-375 in CRC, and miR-375 negatively regulated Wnt/β-catenin signaling by suppressing FZD8. More importantly, FZD8 expression inversely correlated with overall survival in human CRC patients and is a likely independent predictor of survival. Therefore, we concluded that miR-375 functions as a tumor-suppressive microRNA by directly acting upon FZD8, which may serve as a new therapeutic target to inhibit tumor metastasis in CRC.

show abstract

miR-375 regulates the canonical Wnt pathway through FZD8 silencing in arthritis synovial fibroblasts

Cited by 46 publications

References 40 publications

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

Biological Effects of Phosphocitrate on Osteoarthritic Articular Chondrocytes

MicroRNA-375 suppresses human colorectal cancer metastasis by targeting Frizzled 8

Contact Info

Product

Resources

About