scholarly journals ABHD5 inhibits YAP-induced c-Met overexpression and colon cancer cell stemness via suppressing YAP methylation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yan Gu ◽  
Yanrong Chen ◽  
Lai Wei ◽  
Shuang Wu ◽  
Kaicheng Shen ◽  
...  
Keyword(s):  
Histone Methylation ◽  
Nuclear Translocation ◽  
Histone H3 ◽  
Suppressor Gene ◽  
Chromatin Accessibility ◽  
Tumour Suppressor Gene ◽  
Colon Cancer Cell ◽  
Cancer Stemness ◽  
The Core

AbstractCancer stemness represents a major source of development and progression of colorectal cancer (CRC). c-Met critically contributes to CRC stemness, but how c-Met is activated in CRC remains elusive. We previously identified the lipolytic factor ABHD5 as an important tumour suppressor gene in CRC. Here, we show that loss of ABHD5 promotes c-Met activation to sustain CRC stemness in a non-canonical manner. Mechanistically, we demonstrate that ABHD5 interacts in the cytoplasm with the core subunit of the SET1A methyltransferase complex, DPY30, thereby inhibiting the nuclear translocation of DPY30 and activity of SET1A. In the absence of ABHD5, DPY30 translocates to the nucleus and supports SET1A-mediated methylation of YAP and histone H3, which sequesters YAP in the nucleus and increases chromatin accessibility to synergistically promote YAP-induced transcription of c-Met, thus promoting the stemness of CRC cells. This study reveals a novel role of ABHD5 in regulating histone/non-histone methylation and CRC stemness.

scholarly journals ROLE OF TUMOUR SUPPRESSOR GENE P53 IN TRIPLE NEGATIVE BREAST CANCER

2017 ◽  
Vol 5 (4.2) ◽  
pp. 4585-4589
Author(s):  
Priya S Patil ◽  
◽  
Jaydeep N Pol ◽  
Ashalata D Patil ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor

scholarly journals The Role of the Prader-Willi Syndrome Critical Interval for Epigenetic Regulation, Transcription and Phenotype

Epigenomes ◽  
2018 ◽  
Vol 2 (4) ◽  
pp. 18
Author(s):  
Simona Zahova ◽  
Anthony Isles
Keyword(s):  
Histone Methylation ◽  
Neurodevelopmental Disorder ◽  
Molecular Targets ◽  
Prader Willi Syndrome ◽  
Critical Interval ◽  
The Core ◽  
Non Coding Rna ◽  
Nucleolar Rna ◽  
Core Features

Prader-Willi Syndrome (PWS) is a neurodevelopmental disorder caused by loss of expression of the paternally inherited genes on chromosome 15q11.2-q13. However, the core features of PWS have been attributed to a critical interval (PWS-cr) within the 15q11.2-q13 imprinted gene cluster, containing the small nucleolar RNA (snoRNA) SNORD116 and non-coding RNA IPW (Imprinted in Prader-Willi) exons. SNORD116 affects the transcription profile of hundreds of genes, possibly via DNA methylation or post-transcriptional modification, although the exact mechanism is not completely clear. IPW on the other hand has been shown to specifically modulate histone methylation of a separate imprinted locus, the DLK1-DIO3 cluster, which itself is associated with several neurodevelopmental disorders with similarities to PWS. Here we review what is currently known of the molecular targets of SNORD116 and IPW and begin to disentangle their roles in contributing to the Prader-Willi Syndrome phenotype.

Inhibin/activin and ovarian cancer.

2004 ◽  
Vol 11 (1) ◽  
pp. 35-49 ◽  
Author(s):  
D M Robertson ◽  
H G Burger ◽  
P J Fuller
Keyword(s):  
Ovarian Cancer ◽  
Granulosa Cell ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Alpha Subunit ◽  
Beta Subunits ◽  
Granulosa Cell Tumours

Inhibin and activin are members of the transforming growth factor beta (TGFbeta) family of cytokines produced by the gonads, with a recognised role in regulating pituitary FSH secretion. Inhibin consists of two homologous subunits, alpha and either betaA or betaB (inhibin A and B). Activins are hetero- or homodimers of the beta-subunits. Inhibin and free alpha subunit are known products of two ovarian tumours (granulosa cell tumours and mucinous carcinomas). This observation has provided the basis for the development of a serum diagnostic test to monitor the occurrence and treatment of these cancers. Transgenic mice with an inhibin alpha subunit gene deletion develop stromal/granulosa cell tumours suggesting that the alpha subunit is a tumour suppressor gene. The role of inhibin and activin is reviewed in ovarian cancer both as a measure of proven clinical utility in diagnosis and management and also as a factor in the pathogenesis of these tumours. In order to place these findings into perspective the biology of inhibin/activin and of other members of the TGFbeta superfamily is also discussed.

scholarly journals Role of Immunohistochemistry Markers (p53 and CEA), in Study of Colorectal Tumours

2021 ◽  
pp. 94-106
Author(s):  
Sapam Chingkhei Lakpa ◽  
R. Vinoth Kumar ◽  
Mary Lilly
Keyword(s):  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
High Rate ◽  
Common Cancer ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
P53 Tumour Suppressor Gene ◽  
Formalin Fixed ◽  
Colorectal Tumours

Colorectal cancer is the third most common cancer in men and the second in women globally. There is a marked variation in the incidence of colorectal carcinoma worldwide, where western countries having high rate compared to others. p53 tumour suppressor gene is one of the most intensively studied tumour markers in the colorectal tumours. Two markers were used, p53 (oncoprotein p53) and CEA (carcinoembryonic antigen) in the study. The 102 cases of paraffin-embedded samples were processed for the immunohistochemistry examination. After the analysis of the selected patients regarding the antibodies distribution, statistical analysis was performed. The current study showed that there was a statistically significant correlation existing between p53 and CEA in each tumour type irrespective of its histological grades. The immunohistochemistry (IHC) was performed on 4-µm thick sections from 10% formalin- fixed paraffin-embedded tissue blocks.

scholarly journals Histone Demethylase KDM7A Contributes to the Development of Hepatic Steatosis by Targeting Diacylglycerol Acyltransferase 2

2021 ◽  
Vol 22 (20) ◽  
pp. 11085
Author(s):  
Ji-Hyun Kim ◽  
Arukumar Nagappan ◽  
Dae Young Jung ◽  
Nanjoo Suh ◽  
Myeong Ho Jung
Keyword(s):  
Liver Disease ◽  
Hepatic Steatosis ◽  
Histone Methylation ◽  
Functional Role ◽  
Histone H3 ◽  
Diacylglycerol Acyltransferase ◽  
Histone Demethylase ◽  
Nonalcoholic Fatty Liver ◽  
Intracellular Triglyceride

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. While the development of NAFLD is correlated with aberrant histone methylation, modifiers of histone methylation involved in this event remain poorly understood. Here, we studied the functional role of the histone demethylase KDM7A in the development of hepatic steatosis. KDM7A overexpression in AML12 cells upregulated diacylglycerol acyltransferase 2 (DGAT2) expression and resulted in increased intracellular triglyceride (TG) accumulation. Conversely, KDM7A knockdown reduced DGAT2 expression and TG accumulation, and significantly reversed free fatty acids-induced TG accumulation. Additionally, adenovirus-mediated overexpression of KDM7A in mice resulted in hepatic steatosis, which was accompanied by increased expression of hepatic DGAT2. Furthermore, KDM7A overexpression decreased the enrichment of di-methylation of histone H3 lysine 9 (H3K9me2) and H3 lysine 27 (H3K27me2) on the promoter of DGAT2. Taken together, these results indicate that KDM7A overexpression induces hepatic steatosis through upregulation of DGAT2 by erasing H3K9me2 and H3K27me2 on the promoter.

scholarly journals The Cross Marks the Spot: The Emerging Role of JmjC Domain-Containing Proteins in Myeloid Malignancies

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1911
Author(s):  
Hans Felix Staehle ◽  
Heike Luise Pahl ◽  
Jonas Samuel Jutzi
Keyword(s):  
Histone Methylation ◽  
Chromatin Accessibility ◽  
Methyl Groups ◽  
Histone Demethylases ◽  
Histone Tails ◽  
Myeloid Malignancies ◽  
Show Evidence ◽  
Jmjc Domain ◽  
Drug Interventions

Histone methylation tightly regulates chromatin accessibility, transcription, proliferation, and cell differentiation, and its perturbation contributes to oncogenic reprogramming of cells. In particular, many myeloid malignancies show evidence of epigenetic dysregulation. Jumonji C (JmjC) domain-containing proteins comprise a large and diverse group of histone demethylases (KDMs), which remove methyl groups from lysines in histone tails and other proteins. Cumulating evidence suggests an emerging role for these demethylases in myeloid malignancies, rendering them attractive targets for drug interventions. In this review, we summarize the known functions of Jumonji C (JmjC) domain-containing proteins in myeloid malignancies. We highlight challenges in understanding the context-dependent mechanisms of these proteins and explore potential future pharmacological targeting.

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