keyword
https://read.qxmd.com/read/37040760/positive-selection-of-somatically-mutated-clones-identifies-adaptive-pathways-in-metabolic-liver-disease
#21
JOURNAL ARTICLE
Zixi Wang, Shijia Zhu, Yuemeng Jia, Yunguan Wang, Naoto Kubota, Naoto Fujiwara, Ruth Gordillo, Cheryl Lewis, Min Zhu, Tripti Sharma, Lin Li, Qiyu Zeng, Yu-Hsuan Lin, Meng-Hsiung Hsieh, Purva Gopal, Tao Wang, Matt Hoare, Peter Campbell, Yujin Hoshida, Hao Zhu
Somatic mutations in nonmalignant tissues accumulate with age and injury, but whether these mutations are adaptive on the cellular or organismal levels is unclear. To interrogate genes in human metabolic disease, we performed lineage tracing in mice harboring somatic mosaicism subjected to nonalcoholic steatohepatitis (NASH). Proof-of-concept studies with mosaic loss of Mboat7, a membrane lipid acyltransferase, showed that increased steatosis accelerated clonal disappearance. Next, we induced pooled mosaicism in 63 known NASH genes, allowing us to trace mutant clones side by side...
April 27, 2023: Cell
https://read.qxmd.com/read/37036190/targeting-smyd2-inhibits-prostate-cancer-cell-growth-by-regulating-c-myc-signaling
#22
JOURNAL ARTICLE
Junhong Li, Fangning Wan, Junyu Zhang, Shengfeng Zheng, Yunjie Yang, Zhe Hong, Bo Dai
SMYD2 is a lysine histone methyl transferase involved in various cancers epigenetically via methylating histone H3K4, and H3K36. c-Myc is one of the major drivers of prostate cancer (PCa) initiation and progression. The roles of SMYD2 in PCa and the regulators of c-Myc activity in PCa are still under-researched. SMYD2 expression and survival outcomes in PCa cohorts were analyzed by bioinformatics analysis. SMYD2 protein levels were detected in PCa tissues by immunohistochemistry. SMYD2 knockdown cells were established to identify the effects of SMYD2 on cell growth in vitro and in vivo...
April 10, 2023: Molecular Carcinogenesis
https://read.qxmd.com/read/37008071/a-computational-approach-to-predict-the-role-of-genetic-alterations-in-methyltransferase-histones-genes-with-implications-in-liver-cancer
#23
JOURNAL ARTICLE
Tania Isabella Aravena, Elizabeth Valdés, Nicolás Ayala, Vívian D'Afonseca
Histone methyltransferases (HMTs) comprise a subclass of epigenetic regulators. Dysregulation of these enzymes results in aberrant epigenetic regulation, commonly observed in various tumor types, including hepatocellular adenocarcinoma (HCC). Probably, these epigenetic changes could lead to tumorigenesis processes. To predict how histone methyltransferase genes and their genetic alterations (somatic mutations, somatic copy number alterations, and gene expression changes) are involved in hepatocellular adenocarcinoma processes, we performed an integrated computational analysis of genetic alterations in 50 HMT genes present in hepatocellular adenocarcinoma...
2023: Cancer Informatics
https://read.qxmd.com/read/36993727/positive-selection-of-somatically-mutated-clones-identifies-adaptive-pathways-in-metabolic-liver-disease
#24
Zixi Wang, Shijia Zhu, Yuemeng Jia, Yunguan Wang, Naoto Kubota, Naoto Fujiwara, Ruth Gordillo, Cheryl Lewis, Min Zhu, Tripti Sharma, Lin Li, Qiyu Zeng, Yu-Hsuan Lin, Meng-Hsiung Hsieh, Purva Gopal, Tao Wang, Matt Hoare, Peter Campbell, Yujin Hoshida, Hao Zhu
UNLABELLED: Somatic mutations in non-malignant tissues accumulate with age and insult, but whether these mutations are adaptive on the cellular or organismal levels is unclear. To interrogate mutations found in human metabolic disease, we performed lineage tracing in mice harboring somatic mosaicism subjected to non-alcoholic steatohepatitis (NASH). Proof-of-concept studies with mosaic loss of Mboat7 , a membrane lipid acyltransferase, showed that increased steatosis accelerated clonal disappearance...
March 21, 2023: bioRxiv
https://read.qxmd.com/read/36912291/smyd2-expression-its-relationship-to-cytogenetic-and-prognosis-in-a-newly-diagnosed-childhood-b-acute-lymphoblastic-leukemia
#25
JOURNAL ARTICLE
Rania M Gawdat, Sahar A Khalil, Naglaa M Hassan, Reem Nabil, Nevin M Alazhary
BACKGROUND: The SMYD2 gene adjusts lysine residues on histones and non-histone proteins such as transcription factors, signaling kinases, and cell cycle regulators affecting the cell fate and other genes' expression. As it acts as an oncogene, SMYD2's expression levels may affect tumor progression. In this prospective study, our main aim was to determine the association of SMYD2 gene expression with the prognostic parameters of childhood B-acute lymphoblastic leukemia (B-ALL) and evaluate its influence on disease prognosis...
March 1, 2023: Clinical Laboratory
https://read.qxmd.com/read/36838987/targeting-epigenetic-changes-mediated-by-members-of-the-smyd-family-of-lysine-methyltransferases
#26
REVIEW
Alyssa Padilla, John F Manganaro, Lydia Huesgen, Deborah A Roess, Mark A Brown, Debbie C Crans
A comprehensive understanding of the mechanisms involved in epigenetic changes in gene expression is essential to the clinical management of diseases linked to the SMYD family of lysine methyltransferases. The five known SMYD enzymes catalyze the transfer of donor methyl groups from S-adenosylmethionine (SAM) to specific lysines on histones and non-histone substrates. SMYDs family members have distinct tissue distributions and tissue-specific functions, including regulation of development, cell differentiation, and embryogenesis...
February 20, 2023: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/36816359/smyd-family-members-serve-as-potential-prognostic-markers-and-correlate-with-immune-infiltrates-in-gastric-cancer
#27
JOURNAL ARTICLE
Donghui Liu, Menglin Liu, Wenxin Wang, Xiaoxue Li, Enhong Shi, Chenyao Zhang, Yinghui Wang, Yan Zhang, Liru Wang, Xuyao Wang
BACKGROUND: The SMYD family comprises a group of genes encoding lysine methyltransferases, which are closely related to tumorigenesis. However, a systematic understanding of their role in gastric cancer (GC) is lacking. METHODS: Using databases and tools such as the Cancer Genome Atlas, Human Protein Atlas, Kaplan-Meier Plotter, Gene Expression Profiling Interactive Analysis, and Metascape, we comprehensively analyzed differences in SMYD expression and its prognostic value as well as the association of SMYDs with immune cell infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI)...
2023: Journal of Oncology
https://read.qxmd.com/read/36611819/smyd2-promotes-hepatocellular-carcinoma-progression-by-reprogramming-glutamine-metabolism-via-c-myc-gls1-axis
#28
JOURNAL ARTICLE
Kangdi Xu, Jun Ding, Lingfeng Zhou, Dazhi Li, Jia Luo, Wenchao Wang, Mingge Shang, Bingyi Lin, Lin Zhou, Shusen Zheng
Metabolic reprogramming, such as alterations in glutamine metabolism or glycolysis, is the hallmark of hepatocellular carcinoma (HCC). However, the underlying mechanisms are still incompletely elucidated. Previous studies have identified that methyltransferase SET and MYND domain-containing protein 2(SMYD2) is responsible for the pathogenesis of numerous types of cancer. Here, we innovatively uncover how SMYD2 regulates glutamine metabolism in HCC cells and promotes HCC progression. We identified that SMYD2 expression is upregulated in HCC tissues, which correlates with unfavorable clinical outcomes...
December 21, 2022: Cells
https://read.qxmd.com/read/36585926/histone-methyltransferase-smyd2-drives-vascular-aging-by-its-enhancer-dependent-activity
#29
JOURNAL ARTICLE
Zhenghua Su, Haibi Su, Jie Xu, Gang Wei, Lefeng Qu, Ting Ni, Di Yang, Yizhun Zhu
BACKGROUND: Vascular aging is one of the important factors contributing to the pathogenesis of cardiovascular diseases. However, the systematic epigenetic regulatory mechanisms during vascular aging are still unclear. Histone methyltransferase SET and MYND domain-containing protein 2 (Smyd2) is associated with multiple diseases including cancer and inflammatory diseases, but whether it is involved in endothelial cell senescence and aging-related cardiovascular diseases has not been directly proved...
December 28, 2022: Aging
https://read.qxmd.com/read/36411681/effect-of-mirna-200b-on-the-proliferation-of-liver-cancer-cells-via-targeting-smyd2-p53-signaling-pathway
#30
JOURNAL ARTICLE
Weijin Fang, Liying Song, Zuojun Li, Peipei Meng, Shanru Zuo, Shikun Liu
OBJECTIVES: Our previous study has verified that high level of SET and MYND domain-containing protein 2 (SMYD2) plays an important role in acquiring aggressive ability for liver cancer cells in hepatocellular carcinoma. MiR-200b as a tumor suppressor gene involves in a variety of cancers. This study aims to investigate the correlation between miR-200b and SMYD2 in hepatocellular carcinoma and the underlying mechanism. METHODS: Firstly, the levels of SMYD2 and miR-200b in hepatocellular carcinoma tissues and matched adjacent non-tumor liver tissues were tested with real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting...
October 28, 2022: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://read.qxmd.com/read/36346387/clinical-prognostic-value-of-the-smyd2-3-as-new-epigenetic-biomarkers-in-solid-cancer-patients-a-systematic-review-and-meta-analysis
#31
JOURNAL ARTICLE
Mahdieh Razmi, Ayna Yazdanpanah, Shahroo Etemad-Moghadam, Mojgan Alaeddini, Sabrina Angelini, Leila Eini
BACKGROUND: Suppressor of variegation, Enhancer of Zeste, Trithorax (SET) and Myeloid-Nervy-DEAF1 (MYND) domain-containing protein (SMYD) family with methyltransferase activity is involved in cancer progression. This novel meta-analysis aimed to evaluate the association of SMYD family with the clinical and survival outcomes in solid cancer patients. METHODS: We systematically searched Embase, PubMed, Scopus and Web of Science to select relevant articles. Hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals were extracted...
November 8, 2022: Expert Review of Molecular Diagnostics
https://read.qxmd.com/read/36280225/transcriptomic-and-proteomic-time-course-analyses-based-on-metascape-reveal-mechanisms-against-muscle-atrophy-in-hibernating-spermophilus-dauricus
#32
JOURNAL ARTICLE
Kai Dang, Hafiz Muhammad Umer Farooq, Jing Dong, Huajian Yang, Yong Kong, Huiping Wang, Shanfeng Jiang, Yuan Gao, Airong Qian
Hibernating Spermophilus dauricus is resistant to muscle atrophy. Comprehensive transcriptome and proteome time-course analyses based on Metascape can further reveal the underlying processes (pre-hibernation stage, PRE; torpor stage, TOR; interbout arousal stage, IBA; and post-hibernation stage, POST). Transcriptome analysis showed that the cellular responses to growth factor stimulus and discrete oxygen levels continuously changed during hibernation. Proteomic analysis showed that neutrophil degranulation, sulfur compound metabolic process, and generation of precursor metabolites and energy continuously changed during hibernation...
October 21, 2022: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://read.qxmd.com/read/36270984/histone-methyltransferase-smyd2-drives-adipogenesis-via-regulating-stat3-phosphorylation
#33
JOURNAL ARTICLE
Haibi Su, Chen Meng, Jie Xu, Zhenghua Su, Chenxi Xiao, Di Yang
Adipogenesis is a complex cascade involved with the preadipocytes differentiation towards mature adipocytes, accelerating the onset of obesity. Histone methyltransferase SET and MYND domain-containing protein 2 (Smyd2), is involved in a variety of cellular biological functions but the epigenetic regulation of Smyd2 in adipogenesis and adipocyte differentiation remains unclear. Both Smyd2 siRNA and LLY-507, an inhibitor of Smyd2, were used to examine the effect of Smyd2 on adipogenesis and adipocyte differentiation in vitro...
October 21, 2022: Cell Death & Disease
https://read.qxmd.com/read/36191822/the-lysine-methyltransferases-set-and-mynd-domain-containing-2-smyd2-and-enhancer-of-zeste-2-ezh2-co-regulate-osteoblast-proliferation-and-mineralization
#34
JOURNAL ARTICLE
Parisa Dashti, Jeroen van de Peppel, Roman Thaler, Christopher R Paradise, Gary S Stein, Martin A Montecino, Johannes P T M van Leeuwen, Bram J van der Eerden, Amel Dudakovic, Andre J van Wijnen
Bone formation is controlled by histone modifying enzymes that regulate post-translational modifications on nucleosomal histone proteins and control accessibility of transcription factors to gene promoters required for osteogenesis. Enhancer of Zeste homolog 2 (EZH2/Ezh2), a histone H3 lysine 27 (H3K27) methyl transferase, is a suppressor of osteoblast differentiation. Ezh2 is regulated by SET and MYND domain-containing protein 2 (SMYD2/Smyd2), a lysine methyltransferase that modifies both histone and non-histone proteins...
September 30, 2022: Gene
https://read.qxmd.com/read/36157542/mechanistic-and-functional-extrapolation-of-set-and-mynd-domain-containing-protein-2-to-pancreatic-cancer
#35
REVIEW
Eid Alshammari, Ying-Xue Zhang, Zhe Yang
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal neoplasms worldwide and represents the vast majority of pancreatic cancer cases. Understanding the molecular pathogenesis and the underlying mechanisms involved in the initiation, maintenance, and progression of PDAC is an urgent need, which may lead to the development of novel therapeutic strategies against this deadly cancer. Here, we review the role of SET and MYND domain-containing protein 2 (SMYD2) in initiating and maintaining PDAC development through methylating multiple tumor suppressors and oncogenic proteins...
August 7, 2022: World Journal of Gastroenterology: WJG
https://read.qxmd.com/read/36046818/pharmacological-inhibition-of-smyd2-protects-against-cisplatin-induced-acute-kidney-injury-in-mice
#36
JOURNAL ARTICLE
Binbin Cui, Xiying Hou, Mengjun Liu, Qing Li, Chao Yu, Shenglei Zhang, Yi Wang, Jun Wang, Shougang Zhuang, Feng Liu
The histone methyltransferase SET and MYND domain protein 2 (SMYD2) has been implicated in tumorigenesis through methylating histone H3 at lysine36 (H3K36) and some non-histone substrates. Currently, the role of SMYD2 in acute kidney injury (AKI) remains unknown. Here, we investigated the effects of AZ505, a highly selective inhibitor of SMYD2, on the development of AKI and the mechanisms involved in a murine model of cisplatin-induced AKI. SMYD2 and trimethylated histone H3K36 (H3K36Me3) were highly expressed in the kidney following cisplatin treatment; administration of AZ505 remarkedly inhibited their expression, along with improving kidney function and ameliorating kidney damage...
2022: Frontiers in Pharmacology
https://read.qxmd.com/read/35939202/stub1-smyd2-axis-regulates-drug-resistance-in-glioma-cells
#37
JOURNAL ARTICLE
Kailing Pan, Bin Hu, Lude Wang, Jianlie Yuan, Wenxia Xu
SET and MYND domain-containing protein 2 (SMYD2) is an important epigenetic regulator that methylates histone and non-histone proteins. The study aimed to investigate the oncogenic role of SMYD2 in gliomas and explore its degradation mechanism induced by cisplatin. Tumor tissue microarray of 441 patients with glioma was collected for SMYD2 immunohistochemical staining. Kaplan-Meier survival curves were constructed using the overall survival values. mRNA-sequencing analysis was performed for understanding the downstream mechanisms mediated by SMYD2...
August 8, 2022: Journal of Molecular Neuroscience: MN
https://read.qxmd.com/read/35914250/protein-lysine-methyltransferase-smyd2-a-promising-small-molecule-target-for-cancer-therapy
#38
REVIEW
Quan Zheng, Wen Zhang, Guo-Wu Rao
In epigenetic research, the abnormality of protein methylation modification is closely related to the occurrence and development of tumors, which stimulates the interest of researchers in protein methyltransferase research and the efforts to develop corresponding specific small molecule inhibitors. Currently, the protein lysine methyltransferase SMYD2 has been identified as a promising new small molecule target for cancer therapy. But its biological functions have not been fully studied and relatively few inhibitors have been reported, thus this field needs to be further explored...
August 11, 2022: Journal of Medicinal Chemistry
https://read.qxmd.com/read/35884603/oleocanthal-attenuates-metastatic-castration-resistant-prostate-cancer-progression-and-recurrence-by-targeting-smyd2
#39
JOURNAL ARTICLE
Abu Bakar Siddique, Hassan Y Ebrahim, Afsana Tajmim, Judy Ann King, Khaldoun S Abdelwahed, Zakaria Y Abd Elmageed, Khalid A El Sayed
Metastatic castration-resistant prostate cancer (mCRPC) is the most aggressive prostate cancer (PC) phenotype. Cellular lysine methylation is driven by protein lysine methyltransferases (PKMTs), such as those in the SET- and MYND-containing protein (SMYD) family, including SMYD2 methylate, and several histone and non-histone proteins. SMYD2 is dysregulated in metastatic PC patients with high Gleason score and shorter survival. The Mediterranean, extra-virgin-olive-oil-rich diet ingredient S -(-)-oleocanthal (OC) inhibited SMYD2 in biochemical assays and suppressed viability, migration, invasion, and colony formation of PC-3, CWR-R1ca, PC-3M, and DU-145 PC cell lines with IC50 range from high nM to low µM...
July 21, 2022: Cancers
https://read.qxmd.com/read/35759739/crosstalk-between-lysine-methyltransferase-smyd2-and-tgf-%C3%AE-smad3-signaling-promotes-renal-fibrosis-in-autosomal-dominant-polycystic-kidney-disease
#40
JOURNAL ARTICLE
Linda Xiaoyan Li, Ewud Agborbesong, Lu Zhang, Xiaoqin Zhang, Julie Xia Zhou, Xiaogang Li
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited genetic disorder, which is caused by mutations of PKD1 or PKD2 gene and is characterized by renal fluid-filled cyst formation and interstitial fibrosis. PKD1 gene mutation results in the upregulation of SET and MYND domain-containing lysine methyltransferase 2 (SMYD2) in Pkd1 mutant mouse and ADPKD patient kidneys. However, the role and mechanism of Smyd2 in the regulation of renal fibrosis in ADPKD remains elusive. In this study, we show that: 1) the expression of Smyd2 can be regulated by TGF-β-Smad3 in normal rat kidney 49F (NRK-49F) cells and mouse fibroblast NIH3T3 cells; 2) knockdown of Smyd2 and inhibition of Smyd2 with its specific inhibitor, AZ505, decreases TGF-β-induced expression of α-smooth muscle actin (α-SMA), fibronectin, collagens 1 and 3 and plasminogen activator inhibitor-1( PAI1) in NRK-49F cells; 3) Smyd2 regulates the transcription of fibrotic marker genes through binding on the promoters of those genes or through methylating histone H3 to indirectly regulate the expression of those genes; and 4) knockout and inhibition of Smyd2 significantly decreases renal fibrosis in Pkd1 knockout mice, supporting that targeting Smyd2 can not only delay cyst growth but also attenuate renal fibrosis in ADPKD...
June 27, 2022: American Journal of Physiology. Renal Physiology
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