LIVIVO - Search results -

Search results

Result 1 - 10 of total 67

Article ; Online: NF-

Jiang, Yijing / Zhang, Jie / Shi, Conglin / Li, Xingjuan / Jiang, Yongying / Mao, Renfang

Expert reviews in molecular medicine

2023 Volume 25, Page(s) e25

Abstract: The nuclear factor of κ-light chain of enhancer-activated B cells (NF-κB) signaling pathway, which is conserved in invertebrates, plays a significant role in human diseases such as inflammation-related diseases and carcinogenesis. Angiogenesis refers to ... ...

Abstract	The nuclear factor of κ-light chain of enhancer-activated B cells (NF-κB) signaling pathway, which is conserved in invertebrates, plays a significant role in human diseases such as inflammation-related diseases and carcinogenesis. Angiogenesis refers to the growth of new capillary vessels derived from already existing capillaries and postcapillary venules. Maintaining normal angiogenesis and effective vascular function is a prerequisite for the stability of organ tissue function, and abnormal angiogenesis often leads to a variety of diseases. It has been suggested that NK-
MeSH term(s)	Humans ; NF-kappa B/genetics ; NF-kappa B/metabolism ; Signal Transduction ; I-kappa B Proteins/metabolism ; Neoplasms/drug therapy ; Neoplasms/etiology ; Neovascularization, Pathologic/metabolism ; Apoptosis
Chemical Substances	NF-kappa B ; I-kappa B Proteins
Language	English
Publishing date	2023-07-28
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ISSN	1462-3994
ISSN (online)	1462-3994
DOI	10.1017/erm.2023.20
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Cytoplasmic Accumulation of Histones Induced by BET Inhibition Protects Cells from C9orf72 Poly(PR)-Induced Cell Death.

Chen, Miaomiao / Guo, Xiaohong / Guo, Jinjing / Shi, Conglin / Wu, Yuanyuan / Chen, Liuting / Mao, Renfang / Fan, Yihui

Advanced biology

2024 Volume 8, Issue 3, Page(s) e2300334

Abstract: Repeat dipeptides such as poly(proline-arginine) (polyPR) are generated from the hexanucleotide GGGGCC repeat expansions in the C9orf72 gene. These dipeptides are often considered as the genetic cause of familial amyotrophic lateral sclerosis (ALS) and ... ...

Abstract	Repeat dipeptides such as poly(proline-arginine) (polyPR) are generated from the hexanucleotide GGGGCC repeat expansions in the C9orf72 gene. These dipeptides are often considered as the genetic cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In the study, fluorescein isothiocyanate (FITC) labeled PR20 is used to investigate PR20-induced cell death. The findings reveal that the cell death induced by PR20 is dependent on its nuclear distribution and can be blocked by a nuclear import inhibitor called importazole. Further investigation reveals that BRD4 inhibitors, such as JQ-1 and I-BET762, restrict cytoplasmic localization of PR20, thereby reducing its cytotoxic effect. Mechanistically, the inhibition of BRD4 leads to an increase in the expression of numerous histones, resulting in the accumulation of histones in the cytoplasm. These cytoplasmic histones associate with PR20 and limit its distribution within the nucleus. Notably, the ectopic expression of histones alone is enough to confer protection to cells treated with PR20. In addition, phenylephrine (PE) induces cellular hypertrophy and cytoplasmic distribution of histone, which also helps protect cells from PR20-induced cell death. The research suggests that temporarily inducing the presence of cytoplasmic histones may alleviate the neurotoxic effects of dipeptide repeat proteins.
MeSH term(s)	Histones/genetics ; Histones/metabolism ; Histones/pharmacology ; C9orf72 Protein/genetics ; C9orf72 Protein/metabolism ; C9orf72 Protein/pharmacology ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Nuclear Proteins/pharmacology ; DNA Repeat Expansion ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcription Factors/pharmacology ; Dipeptides/genetics ; Dipeptides/metabolism ; Dipeptides/pharmacology ; Cell Death/genetics
Chemical Substances	Histones ; C9orf72 Protein ; Nuclear Proteins ; Transcription Factors ; Dipeptides
Language	English
Publishing date	2024-01-11
Publishing country	Germany
Document type	Journal Article
ISSN	2701-0198
ISSN (online)	2701-0198
DOI	10.1002/adbi.202300334
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: BRD4 inhibitors broadly promote erastin-induced ferroptosis in different cell lines by targeting ROS and FSP1.

Fan, Chenyang / Guo, Xiaohong / Zhang, Jie / Zheng, Wen / Shi, Chonglin / Qin, Yongwei / Shen, Haoliang / Lu, Yang / Fan, Yihui / Li, Yanli / Chen, Liuting / Mao, Renfang

Discover. Oncology

2024 Volume 15, Issue 1, Page(s) 98

Abstract: Ferroptosis, an iron-dependent form of programmed cell death, is a promising strategy for cancer treatment. Bromodomain-containing protein 4 (BRD4) is an epigenetic reader and a promising target for cancer therapeutics. However, the role of BRD4 in ... ...

Abstract	Ferroptosis, an iron-dependent form of programmed cell death, is a promising strategy for cancer treatment. Bromodomain-containing protein 4 (BRD4) is an epigenetic reader and a promising target for cancer therapeutics. However, the role of BRD4 in ferroptosis is controversial and the value of the interaction between BRD4 inhibitors and ferroptosis inducers remains to be explored. Here, we found that BRD4 inhibition greatly enhanced erastin-induced ferroptosis in different types of cells, including HEK293T, HeLa, HepG2, RKO, and PC3 cell lines. Knocking down BRD4 in HEK293T and HeLa cells also promoted erastin-induced cell death. BRD4 inhibition by JQ-1 and I-BET-762 or BRD4 knockdown resulted in substantial accumulation of reactive oxygen species (ROS) in both HEK293T and HeLa cells. The effect of BRD4 inhibition on ferroptosis-associated genes varied in different cells. After using BRD4 inhibitors, the expression of FTH1, Nrf2, and GPX4 increased in HEK293T cells, while the levels of VDAC2, VDAC3, and FSP1 decreased. In HeLa cells, the expression of FTH1, VDAC2, VDAC3, Nrf2, GPX4, and FSP1 was reduced upon treatment with JQ-1 and I-BET-762. Consistently, the level of FSP1 was greatly reduced in HEK293T and HeLa cells with stable BRD4 knockdown compared to control cells. Furthermore, ChIP-sequencing data showed that BRD4 bound to the promoter of FSP1, but the BRD4 binding was greatly reduced upon JQ-1 treatment. Our results suggest that ROS accumulation and FSP1 downregulation are common mechanisms underlying increased ferroptosis with BRD4 inhibitors. Thus, BRD4 inhibitors might be more effective in combination with ferroptosis inducers, especially in FSP1-dependent cancer cells.
Language	English
Publishing date	2024-04-03
Publishing country	United States
Document type	Journal Article
ISSN	2730-6011
ISSN (online)	2730-6011
DOI	10.1007/s12672-024-00928-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: BRD4L cooperates with MYC to block local tumor invasion via suppression of S100A10.

Ma, Yongyi / Liu, Nan / Shi, Yu / Ma, Shuyan / Wang, Yingjun / Zheng, Wen / Sun, Rong / Song, Yihua / Chen, Miaomiao / Qu, Lishuai / Mao, Renfang / Fan, Yihui

Cellular signalling

2024 Volume 119, Page(s) 111173

Abstract: Targeted therapy based on BRD4 and MYC shows promise due to their well-researched oncogenic functions in cancer, but their tumor-suppressive roles are less understood. In this study, we employ a systematic approach to delete exons that encode the low- ... ...

Abstract	Targeted therapy based on BRD4 and MYC shows promise due to their well-researched oncogenic functions in cancer, but their tumor-suppressive roles are less understood. In this study, we employ a systematic approach to delete exons that encode the low-complexity domain (LCD) of BRD4L in cells by using CRISPR-Cas9. In particular, the deletion of exon 14 (BRD4-E14) results in cellular morphological changes towards spindle-shaped and loosely packed. BRD4-E14 deficient cells show increased cell migration and reduced cell adhesion. The expression of S100A10 was significantly increased in cells lacking E14. BRD4L binds with MYC via the E14-encoded region of the LCD to inhibit the expression of S100A10. In cancer tissues, there is a positive correlation between BRD4 and MYC, while both of these proteins are negatively associated with S100A10 expression. Finally, knocking out the BRD4-E14 region or MYC promotes tumor growth in vivo. Together, these data support a tumor-suppressive role of BRD4L and MYC in some contexts. This discovery emphasizes the significance of a discreetly design and precise patient recruitment in clinical trials that testing cancer therapy based BRD4 and MYC.
Language	English
Publishing date	2024-04-09
Publishing country	England
Document type	Journal Article
ZDB-ID	1002702-6
ISSN	1873-3913 ; 0898-6568
ISSN (online)	1873-3913
ISSN	0898-6568
DOI	10.1016/j.cellsig.2024.111173
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2579: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Apolipoprotein A-I Binding Protein Inhibits the Formation of Infantile Hemangioma through Cholesterol-Regulated Hypoxia-Inducible Factor 1α Activation.

Jiang, Yongying / Li, Xingjuan / Liu, Qin / Lei, Gongyun / Wu, Changyue / Chen, Long / Zhao, Yinshuang / Hu, Yae / Xian, Hua / Mao, Renfang

The Journal of investigative dermatology

2023 Volume 144, Issue 3, Page(s) 645–658.e7

Abstract: Infantile hemangioma (IH) is the most frequent vascular tumor of infancy with unclear pathogenesis; disordered angiogenesis is considered to be involved in its formation. Apolipoprotein A-I binding protein (AIBP)-also known as NAXE (NAD [P]HX epimerase)- ... ...

Abstract	Infantile hemangioma (IH) is the most frequent vascular tumor of infancy with unclear pathogenesis; disordered angiogenesis is considered to be involved in its formation. Apolipoprotein A-I binding protein (AIBP)-also known as NAXE (NAD [P]HX epimerase)-a regulator of cholesterol metabolism, plays a critical role in the pathological angiogenesis of mammals. In this study, we found that AIBP had much lower expression levels in both tissues from patients with IH and hemangioma endothelial cells (HemECs) than in adjacent normal tissues and human dermal vascular endothelial cells, respectively. Knockout of NAXE by CRISPR-Cas9 in HemECs enhanced tube formation and migration, and NAXE overexpression impaired tube formation and migration of HemECs. Interestingly, AIBP suppressed the proliferation of HemECs in hypoxia. We then found that reduced expression of AIBP correlated with increased hypoxia-inducible factor 1α levels in tissues from patients with IH and HemECs. Further mechanistic investigation demonstrated that AIBP disrupted hypoxia-inducible factor 1α signaling through cholesterol metabolism under hypoxia. Notably, AIBP significantly inhibited the development of IH in immunodeficient mice. Furthermore, using the validated mouse endothelial cell (ie, EOMA cells) and Naxe
MeSH term(s)	Humans ; Animals ; Mice ; Endothelial Cells/metabolism ; Apolipoprotein A-I/metabolism ; Mice, Knockout ; Hemangioma/genetics ; Cholesterol/metabolism ; Racemases and Epimerases/metabolism ; Hypoxia/metabolism ; Mammals ; Tumor Microenvironment
Chemical Substances	Apolipoprotein A-I ; Cholesterol (97C5T2UQ7J) ; Racemases and Epimerases (EC 5.1.-)
Language	English
Publishing date	2023-10-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2023.07.030
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ui VI Zs.124: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: 1,6-Hexanediol regulates angiogenesis via suppression of cyclin A1-mediated endothelial function

Yongying Jiang / Gongyun Lei / Ting Lin / Nan Zhou / Jintao Wu / Zhou Wang / Yihui Fan / Hongzhuan Sheng / Renfang Mao

BMC Biology, Vol 21, Iss 1, Pp 1-

2023 Volume 17

Abstract: Abstract Background Angiogenesis plays important roles in physiological and pathologic conditions, but the mechanisms underlying this complex process often remain to be elucidated. In recent years, liquid–liquid phase separation (LLPS) has emerged as a ... ...

Abstract	Abstract Background Angiogenesis plays important roles in physiological and pathologic conditions, but the mechanisms underlying this complex process often remain to be elucidated. In recent years, liquid–liquid phase separation (LLPS) has emerged as a new concept to explain many cellular functions and diseases. However, whether LLPS is involved in angiogenesis has not been studied until now. Here, we investigated the potential role of LLPS in angiogenesis and endothelial function. Results We found 1,6-hexanediol (1,6-HD), an inhibitor of LLPS, but not 2,5-hexanediol (2,5-HD) dramatically decreases neovascularization of Matrigel plug and angiogenesis response of murine corneal in vivo. Moreover, 1,6-HD but not 2,5-HD inhibits microvessel outgrowth of aortic ring and endothelial network formation. The endothelial function of migration, proliferation, and cell growth is suppressed by 1,6-HD. Global transcriptional analysis by RNA-sequencing reveals that 1,6-HD specifically blocks cell cycle and downregulates cell cycle-related genes including cyclin A1. Further experimental data show that 1,6-HD treatment greatly reduces the expression of cyclin A1 but with minimal effect on cyclin D1, cyclin E1, CDK2, and CDK4. The inhibitory effect of 1,6-HD on cyclin A1 is mainly through transcriptional regulation because proteasome inhibitors fail to rescue its expression. Furthermore, overexpression of cyclin A1 in HUVECs largely rescues the dysregulated tube formation upon 1,6-HD treatment. Conclusions Our data reveal a critical role of LLPS inhibitor 1,6-HD in angiogenesis and endothelial function, which specifically affects endothelial G1/S transition through transcriptional suppression of CCNA1, implying LLPS as a possible novel player to modulate angiogenesis, and thus, it might represent an interesting therapeutic target to be investigated in clinic angiogenesis-related diseases in future.
Keywords	Angiogenesis ; Endothelial cells ; LLPS ; 1,6-HD ; Cyclin A1 ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: 1,6-Hexanediol regulates angiogenesis via suppression of cyclin A1-mediated endothelial function.

Jiang, Yongying / Lei, Gongyun / Lin, Ting / Zhou, Nan / Wu, Jintao / Wang, Zhou / Fan, Yihui / Sheng, Hongzhuan / Mao, Renfang

BMC biology

2023 Volume 21, Issue 1, Page(s) 75

Abstract: Background: Angiogenesis plays important roles in physiological and pathologic conditions, but the mechanisms underlying this complex process often remain to be elucidated. In recent years, liquid-liquid phase separation (LLPS) has emerged as a new ... ...

Abstract	Background: Angiogenesis plays important roles in physiological and pathologic conditions, but the mechanisms underlying this complex process often remain to be elucidated. In recent years, liquid-liquid phase separation (LLPS) has emerged as a new concept to explain many cellular functions and diseases. However, whether LLPS is involved in angiogenesis has not been studied until now. Here, we investigated the potential role of LLPS in angiogenesis and endothelial function. Results: We found 1,6-hexanediol (1,6-HD), an inhibitor of LLPS, but not 2,5-hexanediol (2,5-HD) dramatically decreases neovascularization of Matrigel plug and angiogenesis response of murine corneal in vivo. Moreover, 1,6-HD but not 2,5-HD inhibits microvessel outgrowth of aortic ring and endothelial network formation. The endothelial function of migration, proliferation, and cell growth is suppressed by 1,6-HD. Global transcriptional analysis by RNA-sequencing reveals that 1,6-HD specifically blocks cell cycle and downregulates cell cycle-related genes including cyclin A1. Further experimental data show that 1,6-HD treatment greatly reduces the expression of cyclin A1 but with minimal effect on cyclin D1, cyclin E1, CDK2, and CDK4. The inhibitory effect of 1,6-HD on cyclin A1 is mainly through transcriptional regulation because proteasome inhibitors fail to rescue its expression. Furthermore, overexpression of cyclin A1 in HUVECs largely rescues the dysregulated tube formation upon 1,6-HD treatment. Conclusions: Our data reveal a critical role of LLPS inhibitor 1,6-HD in angiogenesis and endothelial function, which specifically affects endothelial G1/S transition through transcriptional suppression of CCNA1, implying LLPS as a possible novel player to modulate angiogenesis, and thus, it might represent an interesting therapeutic target to be investigated in clinic angiogenesis-related diseases in future.
MeSH term(s)	Humans ; Mice ; Animals ; Cyclin A1/metabolism ; Human Umbilical Vein Endothelial Cells/metabolism ; Cell Movement ; Neovascularization, Pathologic/genetics ; Neovascularization, Pathologic/metabolism ; Cell Proliferation
Chemical Substances	Cyclin A1 ; hexamethylene glycol (ZIA319275I)
Language	English
Publishing date	2023-04-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2133020-7
ISSN	1741-7007 ; 1741-7007
ISSN (online)	1741-7007
ISSN	1741-7007
DOI	10.1186/s12915-023-01580-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: The generation of PD-L1 and PD-L2 in cancer cells: From nuclear chromatin reorganization to extracellular presentation.

Fan, Zhiwei / Wu, Changyue / Chen, Miaomiao / Jiang, Yongying / Wu, Yuanyuan / Mao, Renfang / Fan, Yihui

Acta pharmaceutica Sinica. B

2021 Volume 12, Issue 3, Page(s) 1041–1053

Abstract: The immune checkpoint blockade (ICB) targeting on PD-1/PD-L1 has shown remarkable promise in treating cancers. However, the low response rate and frequently observed severe side effects limit its broad benefits. It is partially due to less understanding ... ...

Abstract	The immune checkpoint blockade (ICB) targeting on PD-1/PD-L1 has shown remarkable promise in treating cancers. However, the low response rate and frequently observed severe side effects limit its broad benefits. It is partially due to less understanding of the biological regulation of PD-L1. Here, we systematically and comprehensively summarized the regulation of PD-L1 from nuclear chromatin reorganization to extracellular presentation. In PD-L1 and PD-L2 highly expressed cancer cells, a new TAD (topologically associating domain) (chr9: 5,400,000-5,600,000) around
Language	English
Publishing date	2021-09-16
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	2211-3835
ISSN	2211-3835
DOI	10.1016/j.apsb.2021.09.010
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Inhibition of BETs prevents heat shock-induced cell death via upregulating HSPs in SV40 large T antigen transfected cells.

Zhou, Nan / Zhang, Ye / Lei, Gongyun / Chen, Yifan / Lin, Ting / Liu, Qin / Zhao, Yinshuang / Mao, Jiahui / Jiang, Yongying / Mao, Renfang

Genes & genomics

2022 Volume 44, Issue 10, Page(s) 1259–1269

Abstract: Background: Heat shock response is a protected mechanism against environmental changes for the organism, which must be tightly regulated. Bromodomain and extra terminal-containing protein family (BETs) regulate numerous gene expression in many ... ...

Abstract	Background: Heat shock response is a protected mechanism against environmental changes for the organism, which must be tightly regulated. Bromodomain and extra terminal-containing protein family (BETs) regulate numerous gene expression in many physiological and pathological conditions, including viral infection. SV40 is considered as a highly human disease-associated virus. Objective: We aimed to explore whether BETs play a role in heat shock in SV40 large T antigen transfected cells. Methods: SV40LTA was transfected in HeLa cells using the Lipofectamine 8000. BETs inhibitor JQ1 and I-BET-762 was employed to treat transfected cells and HEK-293 T cells. Heat shock treatment was performed to determine the effect of JQ1 and I-BET-762 on these cells. Western blot and quantitative RT-PCR were carried out to assess the expression of HSP70 and other HSPs. Results: We found that inhibition of BETs by JQ1 and I-BET-762 protects cells from heat shock-induced death in HEK293T cells. Both JQ1 and I-BET-762 induce the expression of HSPs and HSF1 in HEK-293 T cells. However, neither JQ1 nor I-BET-762 fail to induce the expression of HSPs in either HeLa or HBL-1 cells. When SV40 large T antigen was transfected into HeLa cells, the induction of HSP70 expressing and the protection of heat shock-induced cell death are reproduced by JQ1 and IBET treatment in these transfected cells. Conclusions: Inhibition of BETs by JQ1 and I-BET-762 prevents heat shock-induced cell death via upregulating HSPs in SV40 large T antigen transfected cells. Our data indicate a novel function of BETs in SV40 large T antigen transformed cells, affecting HSPs and HSF1 as well as its function on heat shock response.
MeSH term(s)	Antigens, Viral, Tumor ; Cell Death ; DNA-Binding Proteins/genetics ; HEK293 Cells ; HSP70 Heat-Shock Proteins/genetics ; HSP70 Heat-Shock Proteins/metabolism ; HeLa Cells ; Heat Shock Transcription Factors/genetics ; Heat-Shock Response ; Humans
Chemical Substances	Antigens, Viral, Tumor ; DNA-Binding Proteins ; HSP70 Heat-Shock Proteins ; Heat Shock Transcription Factors
Language	English
Publishing date	2022-02-17
Publishing country	Korea (South)
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2504587-8
ISSN	2092-9293 ; 1976-9571
ISSN (online)	2092-9293
ISSN	1976-9571
DOI	10.1007/s13258-022-01228-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Details ▾
- Full text online
- Order with fees

Article ; Online: Targeting liquid-liquid phase separation in pancreatic cancer.

Ming, Yue / Chen, Xia / Xu, Yuanpei / Wu, Yuanyuan / Wang, Chenlu / Zhang, Tingting / Mao, Renfang / Fan, Yihui

Translational cancer research

2022 Volume 8, Issue 1, Page(s) 96–103

Abstract: Background: Accumulated evidence suggests a critical role of protein-mediated liquid-liquid phase separation (LLPS) in many key biological processes through organization of membrane-less compartments. However, the pathological role of protein-mediated ... ...

Abstract	Background: Accumulated evidence suggests a critical role of protein-mediated liquid-liquid phase separation (LLPS) in many key biological processes through organization of membrane-less compartments. However, the pathological role of protein-mediated LLPS remains elusive and it is unknown whether protein-mediated LLPS contributes to carcinogenesis. Methods: HPDE6-C7, BxPC-3, PANC-1, AsPC-1 and CFPAC-1 cells were treated with the LLPS inhibitor, 1,6-hexanediol. Cell proliferation was determined by CCK8 assay. An atopic BxPC-3 xenograft mouse model was established and treated with 1,6-hexanediol. Gene expression profiling was achieved by RNA-sequencing. Results: 1,6-hexanediol significantly inhibited cell proliferation and induced cell death in all tested pancreatic cancer cells (BxPC-3, PANC-1, AsPC-1 and CFPAC-1) but had a minimal effect on control cells (HPDE6-C7) at low doses. In an atopic BxPC-3 xenograft model, 1,6-hexanediol significantly limited pancreatic cancer growth. In whole genomic transcriptional analysis, 1,6-hexanediol significantly downregulated the expression of a set of genes that were enriched in cytokine-cytokine receptor interactions, WNT signaling pathway, ECM-receptor interaction, MAPK signaling pathway and focal adhesion. Furthermore, 1,6-hexanediol treatment specifically reduced the expression of MYC but not IL-6 and KLF5. Conclusions: Together, we provided evidence to demonstrate an important role of protein-mediated LLPS in pancreatic cancer. Cancer cells might be more addictive to LLPS and thus disruption of such a process might be a novel way to treat cancer.
Language	English
Publishing date	2022-01-15
Publishing country	China
Document type	Journal Article
ZDB-ID	2901601-0
ISSN	2219-6803 ; 2218-676X
ISSN (online)	2219-6803
ISSN	2218-676X
DOI	10.21037/tcr.2019.01.06
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Details ▾
- Full text online
- Order with fees

To top

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Order via subito