Prolyl 4-hydroxylase 2 promotes B-cell lymphoma progression via hydroxylation of Carabin

Jiang, Wei; Zhou, Xiaoyan; Li, Zengxia; Liu, Kaiyu; Wang, Y. Lynn; Tan, Renke; Cong, Xiaoji; Shan, Jiaoyu; Zhan, Yanxia; Cui, Zheng; Jiang, Lizhi; Li, Quanfu; Shen, Suqin; Bai, Meirong; Cheng, Yunfeng; Li, Bin; Tan, Minjia; Dengke, K.; Liu, Jun O.; Dang, Yongjun

doi:10.1182/blood-2017-07-794875

Cited by 30 publications

(33 citation statements)

References 41 publications

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“…Our GSEA indicated that TBC1D10C6 regulated the KRAS-signaling pathway, which is consistent with the existing research (33). Moreover, ssGSEA revealed that TBC1D10C has a high positive correlation with B cells and T cells, which is consistent with the research of Jiang et al (31) but contradicts Schickel et al (32). The opposing results may be due to study differences, one focused on lymphoid disease while the other was interested in myocardial disease.…”

Section: Discussionsupporting

confidence: 88%

“…GTPase-activating protein (31). Moreover, TBC1D10C physically interacts with CaN T cells and H-Ras in addition to inhibiting Ras/MAPK signaling (31,32). Our GSEA indicated that TBC1D10C6 regulated the KRAS-signaling pathway, which is consistent with the existing research (33).…”

Section: Discussionsupporting

confidence: 87%

“…GTPase-activating protein (31). Moreover, TBC1D10C physically interacts with CaN T cells and H-Ras in addition to inhibiting Ras/MAPK signaling (31,32).…”

Section: Discussionmentioning

confidence: 99%

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Weighted Gene Co-expression Network Analysis Identifies TBC1D10C as A New Prognostic Biomarker for Breast Cancer

Qiao

Pang³

et al. 2021

Preprint

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Background: Immune checkpoint inhibitors are a promising therapeutic strategy for breast cancer (BRCA) patients. The tumor microenvironment (TME) can downregulate the immune response to cancer therapy. Our study aimed to find a TME-related biomarker to identify patients who might respond to immunotherapy. Method: We downloaded raw data from several databases including TCGA and MDACC to identify TME hub genes associated with overall survival (OS) and the progression-free interval (PFI) by WGCNA. Correlations between hub genes and either tumor-infiltrating immune cells or immune checkpoints were conducted by ssGSEA.Result: TME-related green and black modules were selected by WGCNA to further screen hub genes. Random forest, univariate and multivariate Cox regressions were applied to screen hub genes (MYO1G, TBC1D10C, SELPLG, and LRRC15) and construct a nomogram to predict survival of BRCA patients. The C-index for the nomogram was 0.713. A DCA of the predictive model revealed that the net benefit of nomogram was significantly higher than others and the calibration curve demonstrated a good performance by the nomogram. Only TBC1D10C was correlated with both OS and the PFI (both p-values<0.05). TBC1D10C also had a high positive association with tumor-infiltrating immune cells and common immune checkpoints (PD-1, CTLA-4, and TIGIT).Conclusion: We constructed a TME-related gene signature model to predict the survival probability of BRCA patients. We also identified a hub gene, TBC1D10C, which was correlated with both OS and the PFI and had a high positive association with tumor-infiltrating immune cells and common immune checkpoints. TBC1D10C may be a new biomarker to select patients who may benefit from immunotherapy.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 87%

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Weighted Gene Co-expression Network Analysis Identifies TBC1D10C as A New Prognostic Biomarker for Breast Cancer

Qiao

Pang³

et al. 2021

Preprint

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“…In addition, the family of collagen prolyl 4-hydroxylases (P4HAs) has been found to be overexpressed in multiple cancers, promoting cancer progression and is associated with poor clinical outcomes 57,58 . The inhibition of collagen prolyl 4-hydroxylases has been suggested as a strategy to reduce invasiveness of breast cancer 57 and B-cell lymphoma 59 however it remains an unexplored strategy in OS. The primary function of LOX is catalyzing crosslinking of collagens in the extracellular matrix.…”

Section: Discussionmentioning

confidence: 99%

Delineation of hypoxia-induced proteome shifts in osteosarcoma cells with different metastatic propensities

Song

Pearce

Jiang

et al. 2020

Sci Rep

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osteosarcoma (oS) is the most common bone cancer in children and young adults. Solid tumors are characterized by intratumoral hypoxia, and hypoxic cells are associated with the transformation to aggressive phenotype and metastasis. the proteome needed to support an aggressive osteosarcoma cell phenotype remains largely undefined. To link metastatic propensity to a hypoxia-induced proteotype, we compared the protein profiles of two isogenic canine OS cell lines, POS (low metastatic) and HMpoS (highly metastatic), under normoxia and hypoxia. Label-free shotgun proteomics was applied to comprehensively characterize the hypoxia-responsive proteome profiles in the OS cell phenotypes. Hypothesis-driven parallel reaction monitoring was used to validate the differential proteins observed in the shotgun data and to monitor proteins of which we expected to exhibit hypoxia responsiveness, but which were absent in the label-free shotgun data. We established a "distance" score (|z HMPOS − z POS |), and "sensitivity" score (|z Hypoxia − z Normoxia ) to quantitatively evaluate the proteome shifts exhibited by oS cells in response to hypoxia. evaluation of the sensitivity scores for the proteome shifts observed and principal component analysis of the hypoxia-responsive proteins indicated that both cell types acquire a proteome that supports a Warburg phenotype with enhanced cell migration and proliferation characteristics. Cell migration and glucose uptake assays combined with protein function inhibitor studies provided further support that hypoxia-driven adaption of pathways associated with glycolytic metabolism, collagen biosynthesis and remodeling, redox regulation and immunomodulatory proteins typify a proteotype associated with an aggressive cancer cell phenotype. Our findings further suggest that proteins involved in collagen remodeling and immune editing may warrant further evaluation as potential targets for anti-metastatic treatment strategies in osteosarcoma.

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“…There is more evidence shown that PHD2 silencing in cancer cells can exert both pro-and antitumoral effects, depending on the cellular context. On the one hand, PHD2 promotes metastasis through activation of CAFs and inactive PHD2 inhibits proliferation and growth in breast cancer [82], stroma and bone marrow-derived cells [83], lung carcinoma [84], B-cell lymphomas [85], hepatocellular carcinoma [86], and head and neck squamous cell carcinoma [87]. On the other hand, there is some evidence for the antitumoral effect of PHD2 in gastric adenocarcinoma [87], non-small-cell lung cancer [87], and prostate cancer [88].…”

Section: Physical and Chemical Characteristics Of Tmementioning

confidence: 99%

Cellular and Extracellular Components in Tumor Microenvironment and Their Application in Early Diagnosis of Cancers

Wei

Liu

Zhang

et al. 2020

Analytical Cellular Pathology

108

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Tumors are surrounded by complex environmental components, including blood and lymph vessels, fibroblasts, endothelial cells, immune cells, cytokines, extracellular vesicles, and extracellular matrix. All the stromal components together with the tumor cells form the tumor microenvironment (TME). In addition, extracellular physical and chemical factors, including extracellular pH, hypoxia, elevated interstitial fluid pressure, and fibrosis, are closely associated with tumor progression, metastasis, immunosuppression, and drug resistance. Cellular and extracellular components in TME contribute to nearly all procedures of carcinogenesis. By summarizing the recent work in this field, we make a comprehensive review on the role of cellular and extracellular components in the process of carcinogenesis and their potential application in early diagnosis of cancer. We hope that a systematic review of the diverse aspects of TME will help both research scientists and clinicians in this field.

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Prolyl 4-hydroxylase 2 promotes B-cell lymphoma progression via hydroxylation of Carabin

Cited by 30 publications

References 41 publications

Weighted Gene Co-expression Network Analysis Identifies TBC1D10C as A New Prognostic Biomarker for Breast Cancer

Weighted Gene Co-expression Network Analysis Identifies TBC1D10C as A New Prognostic Biomarker for Breast Cancer

Delineation of hypoxia-induced proteome shifts in osteosarcoma cells with different metastatic propensities

Cellular and Extracellular Components in Tumor Microenvironment and Their Application in Early Diagnosis of Cancers

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