High EGFR_1 Inside-Out Activated Inflammation-Induced Motility through SLC2A1-CCNB2-HMMR-KIF11-NUSAP1-PRC1-UBE2C

Zhou, Huilei; Wang, Lin; Huang, Jianing; Jiang, Minghu; Zhang, Xiaoyu; Zhang, Liyuan; Wang, Yangming; Jiang, Ziyi; Zhang, Zhongjie

doi:10.7150/jca.11404

Cited by 12 publications

(6 citation statements)

References 47 publications

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“…Interestingly, the expression of MELK highly correlates with cell cycle genes AURKB , CCNB2 , TOP2A , and UBE2C , which are upregulated in high-grade PC ( Kuner et al , 2013 ) and appear to form a transcriptional network whose expression requires ING3 ( Figure 3A ), suggesting that ING3 regulates this pathway. Similarly, the expression of several genes from the EGFR inside-out pathway ( CCNB2 - HMMR - KIF11 - NUSAP1 - PRC1 - SLC2A1 - UBE2C ) ( Zhou et al , 2015 ) require the expression of ING3 ( Figure 3A ). The requirement of ING3 for the expression of these genes was validated by real-time qPCR ( Figures 3D–J ).…”

Section: Resultsmentioning

confidence: 99%

Human ex vivo prostate tissue model system identifies ING3 as an oncoprotein

et al. 2018

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Background:Although the founding members of the INhibitor of Growth (ING) family of histone mark readers, ING1 and ING2, were defined as tumour suppressors in animal models, the role of other ING proteins in cellular proliferation and cancer progression is unclear.Methods:We transduced ex vivo benign prostate hyperplasia tissues with inducible lentiviral particles to express ING proteins. Proliferation was assessed by H3S10phos immunohistochemistry (IHC). The expression of ING3 was assessed by IHC on a human prostate cancer tissue microarray (TMA). Gene expression was measured by DNA microarray and validated by real-time qPCR.Results:We found that ING3 stimulates cellular proliferation in ex vivo tissues, suggesting that ING3 could be oncogenic. Indeed, ING3 overexpression transformed normal human dermal fibroblasts. We observed elevated levels of ING3 in prostate cancer samples, which correlated with poorer patient survival. Consistent with an oncogenic role, gene-silencing experiments revealed that ING3 is required for the proliferation of breast, ovarian, and prostate cancer cells. Finally, ING3 controls the expression of an intricate network of cell cycle genes by associating with chromatin modifiers and the H3K4me3 mark at transcriptional start sites.Conclusions:Our investigations create a shift in the prevailing view that ING proteins are tumour suppressors and redefine ING3 as an oncoprotein.

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Section: Resultsmentioning

confidence: 99%

Human ex vivo prostate tissue model system identifies ING3 as an oncoprotein

et al. 2018

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“…1 c) included the phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PIK3CB) [ 41 ] and several members of the ubiquitin-proteasome pathway involved in development of inflammatory and autoimmune diseases [ 42 ]. For example, the ubiquitin conjugating enzyme E2-C (UBE2C), which activates several other genes (SLC2A1-CCNB2-HMMR-KIF11-NUSAP1-PRC1-UBE2C), triggering inflammation [ 43 ], and the UCHL5 (or ubiquitin C-terminal hydrolase UCH37), which plays an important role in inflammation and host defense [ 44 ]. Lastly, mRNAs enriched in MetS-EVs encode proteins involved in FGF signaling, a family of proteins which can contribute to pathological conditions by modulating expression of inflammatory cytokines [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

The metabolic syndrome modifies the mRNA expression profile of extracellular vesicles derived from porcine mesenchymal stem cells

Meng

Eirin

Zhu

et al. 2018

Diabetol Metab Syndr

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BackgroundMesenchymal stem cells (MSCs) perform paracrine functions by releasing extracellular vesicles (EVs) containing microRNA, mRNA, and proteins. We investigated the mRNA content of EVs in metabolic syndrome (MetS) and tested hypothesis that comorbidities interfere with the paracrine functionality of MSCs.MethodsMesenchymal stem cells were collected from swine abdominal adipose tissue after 16 weeks of a low- (Lean) or high-calorie (MetS) diet (n = 5 each). We used next-generation mRNAs sequencing to identify mRNAs enriched and depleted in Lean- or MetS-EVs compared to the parent MSCs.ResultsWe found 88 and 130 mRNAs enriched in Lean-EVs and MetS-EVs, respectively, of which only eight were common genes encoding proteins related to the nucleus, endoplasmic reticulum, and membrane fraction. Lean-EVs were enriched with mRNAs primarily involved in transcription regulation and the transforming growth factor (TGF)-β signaling pathway, but devoid of genes related to regulation of inflammation. In contrast, MetS-EVs contained mRNAs involved in translational regulation and modulation of inflammation mediated by chemokines and cytokines, but lacked mRNAs related to TGF-β signaling. mRNAs enriched in EVs have the potential to target a significant proportion of genes enriched in EVs, but only 4% microRNA target genes overlap between Lean- and MetS-EVs. Co-culture with MetS-EVs also increased renal tubular cell inflammation in-vitro.ConclusionsMetabolic syndrome may affect immunomodulatory function of porcine MSCs by modifying mRNA profiles of the EVs that they produce and post-transcriptional regulation. These observations may have important implications for cell-based therapy, and support development of strategies to improve the efficacy of MSCs and their EVs.Electronic supplementary materialThe online version of this article (10.1186/s13098-018-0359-9) contains supplementary material, which is available to authorized users.

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“…Cyclin B2 (CCNB2), which belongs to B-type cyclins, is a cell cycle regulator [ 6 ]. A previous study indicated that CCNB2 was synthesized at G1 phase and quickly downregulated at anaphase [ 7 ]. During cell cycle, the defects of CCNB2 led to the failure of G2/M checkpoint and stimulated gene mutations and tumorigenesis [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Cyclin B2 (CCNB2) Stimulates the Proliferation of Triple-Negative Breast Cancer (TNBC) Cells In Vitro and In Vivo

Jia

2021

Disease Markers

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Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Currently, targeting therapy makes great advances for the treatment of TNBC, whereas more effective therapeutic targets are urgently needed. Cyclin B2 (CCNB2), which belongs to B-type cyclins, is known as a cell cycle regulator. CCNB2 is synthesized at G1 phase in cancer cells and downregulated at anaphase. The defects of CCNB2 led to the abnormal cell cycle and tumorigenesis. Though there are wide effects of CCNB2 on multiple types of tumors, the potential role of CCNB2 in TNBC progression is still unclear. Herein, we found that CCNB2 was highly expressed in human TNBC tissues and correlated with the prognosis and clinical pathological features including tumor size ( p = 0.022 ∗ ) and pTNM stage ( p = 0.021 ∗ ) of patients with TNBC. CCNB2 could promote the proliferation of TNBC cells in vitro and in mice. Our findings therefore confirmed the involvement of CCNB2 in TNBC progression and provided the evidence that CCNB2 could serve as a promising molecular target of TNBC.

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High EGFR_1 Inside-Out Activated Inflammation-Induced Motility through SLC2A1-CCNB2-HMMR-KIF11-NUSAP1-PRC1-UBE2C

Cited by 12 publications

References 47 publications

Human ex vivo prostate tissue model system identifies ING3 as an oncoprotein

Human ex vivo prostate tissue model system identifies ING3 as an oncoprotein

The metabolic syndrome modifies the mRNA expression profile of extracellular vesicles derived from porcine mesenchymal stem cells

Cyclin B2 (CCNB2) Stimulates the Proliferation of Triple-Negative Breast Cancer (TNBC) Cells In Vitro and In Vivo

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