Over-expression of Thrombospondin 4 correlates with loss of miR-142 and contributes to migration and vascular invasion of advanced hepatocellular carcinoma

Su, Fang; Zhao, Jun; Qin, Shukui; Wang, Rui; Li, Yumei; Wang, Qiang; Tan, Yulin; Jin, Hao; Zhu, Fangquan; Ou, Yurong; Ze-nong, Cheng; Su, Wenyu; Zhao, Fuyou; Yang, Yan; Zhou, Zhengguang; Zheng, Jiyue; Li, Yawei; Li, Zhongwen; Wu, Qiong

doi:10.18632/oncotarget.15054

Cited by 40 publications

(40 citation statements)

References 28 publications

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“…High expression of TSP4 in remodeling tissues, particularly in heart disease and cancer [5][6][7][8][9][10][11][12][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29], suggested that this matricellular protein may regulate fibrosis and angiogenesis. The effects of TSP-4 on matrix remodeling has been demonstrated in Thbs4 -/mice by us and others [5][6][7]45], and we recently reported that TSP4 is pro-angiogenic [24,25] in contrast to the prominent role of TSP-1 as an anti-angiogeneic protein [2,54,55].…”

Section: Discussionmentioning

confidence: 99%

“…High levels of TSP4 have been detected in remodeling and failing hearts [3][4][5][6][7], several cancers [8][9][10][11][12][13], and atherosclerotic lesions [14]. Recently, new functions have been ascribed to TSP4 in cardiovascular system [5][6][7][14][15][16][17][18][19][20][21][22][23][24][25], cancer [8][9][10][11][12][24][25][26][27][28][29], and nervous system [30][31][32][33][34], but effects of TSP4 on cellular responses and the regulation of TSP4 expression remain poorly understood. For example, with an exception of TGF-beta [25], stimuli inducing TSP4 expression in tissues remain unknown.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Thrombospondin-4 on Pro-inflammatory Phenotype Differentiation and Apoptosis in Macrophages

Rahman

Muppala

et al. 2019

Preprint

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Thrombospondin-4 (TSP4) attracted a lot of attention recently as a result of new functions identified for this matricellular protein in cardiovascular, muscular, and nervous systems. We have previously reported that TSP4 promotes local vascular inflammation in mouse atherosclerosis model. A common variant of TSP4, P387-TSP4, was associated with increased cardiovascular disease risk in human population studies. In a mouse atherosclerosis model, TSP4 had profound effect on accumulation of macrophages in lesions, which prompted us to examine its effects on macrophages, more in detail in this report.We examined the effects of A387-TSP-4 and P387-TSP-4 on mouse macrophages in cell culture and in vivo in the model of LPS-induced peritonitis. In tissues and in cell culture, TSP4 expression was associated with inflammation: TSP4 expression was upregulated in peritoneal tissues in LPS-induced peritonitis, and pro-inflammatory signals, INFg, GM-CSF, and LPS, induced TSP4 expression in macrophages in vivo and in cell culture. Deficiency in TSP-4 in macrophages from Thbs4 -/mice reduced the expression of pro-inflammatory macrophage markers, suggesting that TSP-4 facilitates macrophage differentiation into pro-inflammatory phenotype. Expression of TSP4, especially more active P387-TSP4, was associated with higher cellular apoptosis. Cultured macrophages displayed increased adhesion to TSP4 and reduced migration in presence of TSP4, and these responses were further increased with P387 variant.We concluded that TSP4 expression in tissue macrophages and in cultured macrophages increases their accumulation in tissues during the acute inflammatory process and supports macrophage differentiation into a pro-inflammatory phenotype. In a model of acute inflammation, TSP4 supports pro-inflammatory macrophage apoptosis, a response that is closely related to their pro-inflammatory activity and release of pro-inflammatory signals. P387-TSP4 was found to be more active form of TSP4 in all examined functions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of Thrombospondin-4 on Pro-inflammatory Phenotype Differentiation and Apoptosis in Macrophages

Rahman

Muppala

et al. 2019

Preprint

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“…High levels of TSP-4 have been detected in remodeling and failing hearts [3][4][5][6][7] , several cancers [8][9][10][11][12][13] , and atherosclerotic lesions 14 . Recently, new functions have been ascribed to TSP-4 in the cardiovascular system [5][6][7][14][15][16][17][18][19][20][21][22][23][24][25] , cancer [8][9][10][11][12][24][25][26][27][28][29] , skeletal muscle 30,31 , and nervous system [32][33][34][35][36] , but effects of TSP-4 on cellular responses and the regulation of TSP-4 expression remain poorly understood. For example, with an exception of TGFbeta 25 , stimuli inducing TSP-4 expression in tissues remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Effects of thrombospondin-4 on pro-inflammatory phenotype differentiation and apoptosis in macrophages

Rahman

Muppala

et al. 2020

Cell Death Dis

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Thrombospondin-4 (TSP-4) attracted renewed attention recently as a result of assignment of new functions to this matricellular protein in cardiovascular, muscular, and nervous systems. We have previously reported that TSP-4 promotes local vascular inflammation in a mouse atherosclerosis model. A common variant of TSP-4, P387-TSP-4, was associated with increased cardiovascular disease risk in human population studies. In a mouse atherosclerosis model, TSP-4 had profound effect on accumulation of macrophages in lesions, which prompted us to examine its effects on macrophages in more detail. We examined the effects of A387-TSP-4 and P387-TSP-4 on mouse macrophages in cell culture and in vivo in the model of LPS-induced peritonitis. In tissues and in cell culture, TSP-4 expression was associated with inflammation: TSP-4 expression was upregulated in peritoneal tissues in LPS-induced peritonitis, and pro-inflammatory signals, INFγ, GM-CSF, and LPS, induced TSP-4 expression in macrophages in vivo and in cell culture. Deficiency in TSP-4 in macrophages from Thbs4 −/− mice reduced the expression of pro-inflammatory macrophage markers, suggesting that TSP-4 facilitates macrophage differentiation into a pro-inflammatory phenotype. Expression of TSP-4, especially more active P387-TSP-4, was associated with higher cellular apoptosis. Cultured macrophages displayed increased adhesion to TSP-4 and reduced migration in presence of TSP-4, and these responses were further increased with P387 variant. We concluded that TSP-4 expression in macrophages increases their accumulation in tissues during the acute inflammatory process and supports macrophage differentiation into a pro-inflammatory phenotype. In a model of acute inflammation, TSP-4 supports pro-inflammatory macrophage apoptosis, a response that is closely related to their pro-inflammatory activity and release of pro-inflammatory signals. P387-TSP-4 was found to be the more active form of TSP-4 in all examined functions.

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“…The breast-related gene explored by Huang et al [32] contains the gene THBS4, which is up-regulated in breast cancer. In the study of hepatocellular carcinoma, Su et al [33] found that knockdown of ThBS4 inhibited migration and invasion of hepatocellular carcinoma cells, as well as hemangiocarcinoma-induced angiogenesis. THBS4 as a target is very promising for the treatment of advanced liver cancer.…”

Section: Discussionmentioning

confidence: 99%

Time series expression pattern of key genes reveals the molecular process of esophageal cancer

2020

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Correspondence: Yurong Sun (supiaoy66@163.com) Background: Esophageal cancer is one of the most poorly diagnosed and fatal cancers in the world. Although a series of studies on esophageal cancer have been reported, the molecular pathogenesis of the disease is still elusive. Aim: To investigate the molecular process of esophageal cancer comprehensively and deeply. Methods: Differential expression analysis was performed to identify differentially expressed genes (DEGs) in different stages of esophageal cancer. Then exacting gene interaction modules and hub genes were identified in module interaction network. Further, though survival analysis, methylation analysis, pivot analysis, and enrichment analysis, some important molecules and related function or pathway were identified to elucidate potential mechanism in esophageal cancer. Results: A total of 7457 DEGs and 14 gene interaction modules were identified. These module genes were significantly involved in the positive regulation of protein transport, gastric acid secretion, insulin-like growth factor receptor binding and other biological processes (BPs), as well as p53 signaling pathway, ERBB signaling pathway and epidermal growth factor receptor (EGFR) signaling pathway. Then, transcription factors (TFs) (including HIF1A) and ncRNAs (including CRNDE and hsa-mir-330-3p) significantly regulate dysfunction modules were identified. Further, survival analysis showed that GNGT2 was closely related to survival of esophageal cancer. And DEGs with strong methylation regulation ability were identified, including SST and SH3GL2. Conclusion: These works not only help us to reveal the potential regulatory factors in the development of disease, but also deepen our understanding of its deterioration mechanism.

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Over-expression of Thrombospondin 4 correlates with loss of miR-142 and contributes to migration and vascular invasion of advanced hepatocellular carcinoma

Cited by 40 publications

References 28 publications

Effect of Thrombospondin-4 on Pro-inflammatory Phenotype Differentiation and Apoptosis in Macrophages

Effect of Thrombospondin-4 on Pro-inflammatory Phenotype Differentiation and Apoptosis in Macrophages

Effects of thrombospondin-4 on pro-inflammatory phenotype differentiation and apoptosis in macrophages

Time series expression pattern of key genes reveals the molecular process of esophageal cancer

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