191 results match your criteria kdm3a

[Identification of hypoxia-specific therapeutic targets in multiple myeloma].

Sho Ikeda

Rinsho Ketsueki 2021 ;62(4):305-313

Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine.

The bone marrow microenvironment is low in oxygen, promoting a hypoxic response which causes myeloma cells to acquire stem cell properties and enhanced therapy resistance. We performed comprehensive gene and microRNA expression analyses of samples from myeloma patients and cell lines cultured under hypoxia. Through this, we identified the histone demethylase KDM3A, the glycolytic enzyme HK2, and microRNA-210 as factors playing important roles in the behavior of cells under hypoxic conditions. Read More

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Downregulation of miR-335 exhibited an oncogenic effect via promoting KDM3A/YAP1 networks in clear cell renal cell carcinoma.

Cancer Gene Ther 2021 Apr 23. Epub 2021 Apr 23.

Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer affecting many people worldwide. Although the 5-year survival rate is 65% in localized disease, after metastasis, the survival rate is <10%. Emerging evidence has shown that microRNAs (miRNAs) play a crucial regulatory role in the progression of ccRCC. Read More

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The long non-coding RNA SNHG4/microRNA-let-7e/KDM3A/p21 pathway is involved in the development of non-small cell lung cancer.

Mol Ther Oncolytics 2021 Mar 25;20:634-645. Epub 2020 Dec 25.

Department of Respiratory Medicine, Linyi People's Hospital, Linyi 276000, Shandong Province, P.R. China.

Non-small cell lung cancer (NSCLC) is a foremost cause of malignancy-associated mortality globally. Recent studies have emphasized long non-coding RNAs (lncRNAs) as important biomarkers with diagnostic and therapeutic potential in regard to NSCLC. This study aimed to elucidate the functional role of lncRNA small nucleolar RNA host gene 4 (SNHG4) in NSCLC. Read More

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Myocardin-related transcription factor A (MRTF-A) regulates integrin beta 2 transcription to promote macrophage infiltration and cardiac hypertrophy in mice.

Cardiovasc Res 2021 Mar 22. Epub 2021 Mar 22.

Key Laboratory of Targeted Intervention of Cardiovascular Disease and Collaborative Innovation Center for Cardiovascular Translational Medicine, Department of Pathophysiology, Nanjing Medical University, Nanjing, China.

Aims: Macrophage-mediated inflammatory response represents a key pathophysiological process in a host of cardiovascular diseases including heart failure. Regardless of etiology, heart failure is invariably preceded by cardiac hypertrophy. In the present study we investigated the effect of macrophage-specific deletion of myocardin-related transcription factor A (MRTF-A) on cardiac hypertrophy and the underlying mechanism. Read More

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NG2/CSPG4, CD146/MCAM and VAP1/AOC3 are regulated by myocardin-related transcription factors in smooth muscle cells.

Sci Rep 2021 Mar 16;11(1):5955. Epub 2021 Mar 16.

Department of Experimental Medical Science, BMC D12, Lund University, 22184, Lund, Sweden.

The present work addressed the hypothesis that NG2/CSPG4, CD146/MCAM, and VAP1/AOC3 are target genes of myocardin-related transcription factors (MRTFs: myocardin/MYOCD, MRTF-A/MKL1, MRTF-B/MKL2) and serum response factor (SRF). Using a bioinformatics approach, we found that CSPG4, MCAM, and AOC3 correlate with MYOCD, MRTF-A/MKL1, and SRF across human tissues. No other transcription factor correlated as strongly with these transcripts as SRF. Read More

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MicroRNA-194 acts as a suppressor during abdominal aortic aneurysm via inhibition of KDM3A-mediated BNIP3.

Life Sci 2021 Mar 1;277:119309. Epub 2021 Mar 1.

Department of Vascular Surgery, The First Hospital of Jilin University, Changchun 130021, PR China. Electronic address:

Aims: Abdominal aortic aneurysm (AAA) is a serious disorder with a high disability rates and mortality rates. Accumulating evidence has identified the vital functions of microRNAs (miRNAs) in the treatment of AAA. Hence, this study is aimed at exploring the modulatory role of miR-194 in the development of AAA. Read More

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Tumor-Suppressive Role of microRNA-202-3p in Hepatocellular Carcinoma Through the KDM3A/HOXA1/MEIS3 Pathway.

Front Cell Dev Biol 2020 15;8:556004. Epub 2021 Jan 15.

Department of Organ Transplantation and Hepatobiliary, Key Laboratory of Organ Transplantation of Liaoning Province, The First Affiliated Hospital, China Medical University, Shenyang, China.

Hepatocellular carcinoma (HCC) represents a malignant tumor predominantly arising in the setting of cirrhosis and is the third most common cause of cancer-associated death on a global scale. The heterogeneous nature of HCC and limited well-recognized biomarkers may contribute to poor patient prognosis and treatment failure. In this study, we identified expression pattern of microRNA-202-3p (miR-202-3p) in HCC and characterized its functional role as well as related mechanisms. Read More

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January 2021

microRNA-155-3p attenuates intervertebral disc degeneration via inhibition of KDM3A and HIF1α.

Inflamm Res 2021 Mar 23;70(3):297-308. Epub 2021 Jan 23.

Spine Surgery, Luoyang Orthopedic Hospital of Henan Province, No. 100 Yongping Road, Henan, 450000, Zhengzhou, China.

Objective: Intervertebral disc degeneration (IDD) is a key element resulting in low back pain, but the mechanisms underlying IDD remain largely unknown. The purpose of the study was to investigate the influence of microRNA-155-3p (miR-155-3p) on proliferation and autophagy of nucleus pulposus (NP) cells in IDD with the involvement of hypoxia-inducible factor 1 α (HIF1α)/histone lysine demethylase 3A (KDM3A) axis.

Methods: IDD NP tissues of patients with lumbar disc herniation and traumatic intervertebral disc NP tissues from patients with traumatic lumbar fracture were collected. Read More

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Effect of Hypoxia on Proliferation and the Expression of the Genes HIF-1α and JMJD1A in Head and Neck Squamous Cell Carcinoma Cell Lines.

Anticancer Res 2021 Jan;41(1):113-122

Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, Julius Maximilian University of Wuerzburg, Wuerzburg, Germany.

Background/aim: The aim of the study was to investigate the effects of hypoxia on proliferation and the expression of HIF-1α (hypoxia-inducible factor 1 alpha) and JMJD1A (jumonji domain 1A) in head and neck squamous cell carcinoma (HNSCC).

Materials And Methods: FaDu and HLaC78 cells were incubated for 1-24 h in hypoxia and normoxia. Cell proliferation, mRNA and protein levels of HIF-1α and JMJD1A were quantified by counting, PCR and western blot. Read More

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January 2021

Magnoflorine Ameliorates Inflammation and Fibrosis in Rats With Diabetic Nephropathy by Mediating the Stability of Lysine-Specific Demethylase 3A.

Front Physiol 2020 22;11:580406. Epub 2020 Dec 22.

Department of Nephrology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Diabetic nephropathy (DN) represents one of the most devastating complications for patients with diabetes. The anti-diabetic activities of Magnoflorine (MF) were reported, with underlying mechanism unknown. Lysine-specific demethylase 3A (KDM3A) was identified in the renal injuries. Read More

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December 2020

Down-regulated microRNA-199a-3p enhances osteogenic differentiation of bone marrow mesenchymal stem cells by targeting Kdm3a in ovariectomized rats.

Biochem J 2021 Feb;478(4):721-734

Department of Orthopaedics, The Affiliated Hospital of Nantong University, Nantong 226001, P.R. China.

Osteoporosis is a prevalent systemic skeletal disorder entailing bone fragility and increased fracture risk, often emerging in post-menopausal life. Emerging evidence implicates the dysregulation of microRNAs (miRNAs or miRs) in the progression of osteoporosis. This study investigated the effect of miR-199a-3p on osteoporosis and its underlying mechanism. Read More

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February 2021

Extracellular vesicles-encapsulated let-7i shed from bone mesenchymal stem cells suppress lung cancer via KDM3A/DCLK1/FXYD3 axis.

J Cell Mol Med 2021 Feb 22;25(4):1911-1926. Epub 2020 Dec 22.

Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.

Accumulating evidence has suggested that extracellular vesicles (EVs) play a crucial role in lung cancer treatment. Thus, we aimed to investigate the modulatory role of bone marrow mesenchymal stem cell (BMSC)-EV-derived let-7i and their molecular mechanism in lung cancer progression. Microarray-based analysis was applied to predict lung cancer-related miRNAs and their downstream genes. Read More

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February 2021

overexpression in men with nonobstructive azoospermia: A case-control study.

Int J Reprod Biomed 2020 Nov 22;18(11):961-968. Epub 2020 Nov 22.

Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.

Background: The role of and its downstream genes in male fertility has been approved in animal models. Additionally, the expression shrinkage of is significantly correlated with human azoospermia phenotype. Aberrant expression of micro-RNAs could mislead spermatogenesis and mostly lead to diverse phenotypes of male infertility. Read More

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November 2020

JmjC-KDMs KDM3A and KDM6B modulate radioresistance under hypoxic conditions in esophageal squamous cell carcinoma.

Cell Death Dis 2020 12 14;11(12):1068. Epub 2020 Dec 14.

Cancer Biology & Epigenetics Group - Research Center, Portuguese Oncology Institute of Porto (CI-IPOP), Porto, Portugal.

Esophageal squamous cell carcinoma (ESCC), the most frequent esophageal cancer (EC) subtype, entails dismal prognosis. Hypoxia, a common feature of advanced ESCC, is involved in resistance to radiotherapy (RT). RT response in hypoxia might be modulated through epigenetic mechanisms, constituting novel targets to improve patient outcome. Read More

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December 2020

Epigenetic Regulation of Wnt Signaling by Carboxamide-Substituted Benzhydryl Amines that Function as Histone Demethylase Inhibitors.

iScience 2020 Dec 13;23(12):101795. Epub 2020 Nov 13.

Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY 40536-0509, USA.

Aberrant activation of Wnt signaling triggered by mutations in either () or (β-catenin) is a hallmark of colorectal cancers (CRC). As part of a program to develop epigenetic regulators for cancer therapy, we developed carboxamide-substituted benzhydryl amines (CBAs) bearing either aryl or heteroaryl groups that selectively targeted histone lysine demethylases (KDMs) and functioned as inhibitors of the Wnt pathway. A biotinylated variant of -((5-chloro-8-hydroxyquinolin-7-yl) (4-(diethylamino)phenyl)-methyl)butyramide (CBA-1) identified KDM3A as a binding partner. Read More

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December 2020

Histone Demethylase Promotes Cervical Cancer Malignancy Through the /KIF14/Hedgehog Axis.

Onco Targets Ther 2020 19;13:11957-11973. Epub 2020 Nov 19.

Department of Gynecological Oncology Radiotherapy, Jilin Cancer Hospital, Changchun 130012, Jilin, People's Republic of China.

Background: Lysine demethylase 3A () has been increasingly recognized as an important epigenetic regulator involved in cancer development. This study aims to explore the relevance of to cervical cancer (CC) progression and the molecules involved.

Materials And Methods: Tumor and the adjacent tissues from CC patients were collected. Read More

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November 2020

Epigenetic and Transcriptional Control of the Epidermal Growth Factor Receptor Regulates the Tumor Immune Microenvironment in Pancreatic Cancer.

Cancer Discov 2021 Mar 6;11(3):736-753. Epub 2020 Nov 6.

Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Although immunotherapy has revolutionized cancer care, patients with pancreatic ductal adenocarcinoma (PDA) rarely respond to these treatments, a failure that is attributed to poor infiltration and activation of T cells in the tumor microenvironment (TME). We performed an CRISPR screen and identified lysine demethylase 3A (KDM3A) as a potent epigenetic regulator of immunotherapy response in PDA. Mechanistically, KDM3A acts through Krueppel-like factor 5 (KLF5) and SMAD family member 4 (SMAD4) to regulate the expression of the epidermal growth factor receptor (EGFR). Read More

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KDM3A regulates Slug expression to promote the invasion of MCF7 breast cancer cells in hypoxia.

Oncol Lett 2020 Dec 7;20(6):335. Epub 2020 Oct 7.

Personalized Genomic Medicine Research Centre, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.

Oxygen deprivation (hypoxia), which frequently occurs in the tumour microenvironment, is a strong driver of the phenotypic transition of cancer cells. An increase in metastatic potential such as cell invasion is a well-known phenotypical change induced in hypoxia. The present study demonstrated that lysine demethylase 3A (KDM3A), a Jumonji C domain-containing KDM, is involved in the hypoxia-induced invasion of MCF7 breast cancer cells. Read More

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December 2020

Metabolic and energetic benefits of microRNA-22 inhibition.

BMJ Open Diabetes Res Care 2020 10;8(1)

Clore Laboratory, University of Buckingham, Buckingham, UK.

Introduction: We previously demonstrated in primary cultures of human subcutaneous adipocytes and in a mouse model of diet-induced obesity that specific microRNA-22-3p antagomirs produce a significant reduction of fat mass and an improvement of several metabolic parameters. These effects are related to the activation of target genes such as , , , and involved in lipid catabolism, thermogenesis, insulin sensitivity and glucose homeostasis.

Research Design And Methods: We now report a dedicated study exploring over the course of 3 months the metabolic and energetic effects of subcutaneous administration of our first miR-22-3p antagomir drug candidate (APT-110) in adult C57BL/6 male mice. Read More

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October 2020

MiR-216a-5p alleviates chronic constriction injury-induced neuropathic pain in rats by targeting KDM3A and inactivating Wnt/β-catenin signaling pathway.

Neurosci Res 2020 Sep 2. Epub 2020 Sep 2.

Department of Anesthesiology, The Affiliated Huxi Hospital of Jining Medical College, Shanxian Central Hospital, Shanxian 274300, Shandong, China. Electronic address:

Neuropathic pain is a devastating disease and exists tolerance to current available analgesics. MicroRNAs were reported to be involved in the regulation of neuropathic pain, but the biological role of miR-216a-5p in neuropathic pain remains unclear. In this study, we constructed a CCI rat model of neuropathic pain. Read More

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September 2020

Incorporating multiple sets of eQTL weights into gene-by-environment interaction analysis identifies novel susceptibility loci for pancreatic cancer.

Genet Epidemiol 2020 11 10;44(8):880-892. Epub 2020 Aug 10.

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.

It is of great scientific interest to identify interactions between genetic variants and environmental exposures that may modify the risk of complex diseases. However, larger sample sizes are usually required to detect gene-by-environment interaction (G × E) than required to detect genetic main association effects. To boost the statistical power and improve the understanding of the underlying molecular mechanisms, we incorporate functional genomics information, specifically, expression quantitative trait loci (eQTLs), into a data-adaptive G × E test, called aGEw. Read More

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November 2020

Histone demethylase Jumonji domain-containing 1A inhibits proliferation and progression of gastric cancer by upregulating runt-related transcription factor 3.

Cancer Sci 2020 Oct 6;111(10):3679-3692. Epub 2020 Sep 6.

Department of Cell Biology, Key Laboratory of Cell Biology, National Health Commission of the PRC, Shenyang, China.

The histone demethylase Jumonji domain-containing 1A (JMJD1A) is overexpressed in multiple cancers and promotes cancer progression. However, the role and mechanism of JMJD1A in gastric cancer (GC) remains poorly understood. Here, we found that JMJD1A could suppress GC cell proliferation and xenograft tumor growth. Read More

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October 2020

BRG1 Stimulates Endothelial Derived Alarmin MRP8 to Promote Macrophage Infiltration in an Animal Model of Cardiac Hypertrophy.

Front Cell Dev Biol 2020 7;8:569. Epub 2020 Jul 7.

Key Laboratory of Targeted Intervention of Cardiovascular Disease and Collaborative Innovation Center for Cardiovascular Disease, Department of Pathophysiology, Nanjing Medical University, Nanjing, China.

Endothelial cell derived angiocrine factors contribute to the disruption of homeostasis and the pathogenesis of cardiovascular diseases in response to stress stimuli. In the present study we investigated the role of BRG1, a key component of the chromatin remodeling complex, in the regulation of angiocrine signaling. We report that angiotensin II (Ang II) induced pathological cardiac hypertrophy was attenuated in mice with endothelial-specific ablation of BRG1 (ecKO) compared to the control mice (WT). Read More

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KDM3A/Ets1 epigenetic axis contributes to PAX3/FOXO1-driven and independent disease-promoting gene expression in fusion-positive Rhabdomyosarcoma.

Mol Oncol 2020 10 5;14(10):2471-2486. Epub 2020 Aug 5.

Department of Pathology, Anschutz Medical Campus, University of Colorado Denver, Aurora, CO, USA.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and young adults. RMS exists as two major disease subtypes, oncofusion-negative RMS (FN-RMS) and oncofusion-positive RMS (FP-RMS). FP-RMS is characterized by recurrent PAX3/7-FOXO1 driver oncofusions and is a biologically and clinically aggressive disease. Read More

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October 2020

Crucial Functions of the JMJD1/KDM3 Epigenetic Regulators in Cancer.

Mol Cancer Res 2021 01 30;19(1):3-13. Epub 2020 Jun 30.

Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.

Epigenetic changes are one underlying cause for cancer development and often due to dysregulation of enzymes modifying DNA or histones. Most Jumonji C domain-containing (JMJD) proteins are histone lysine demethylases (KDM) and therefore epigenetic regulators. One JMJD subfamily consists of JMJD1A/KDM3A, JMJD1B/KDM3B, and JMJD1C/KDM3C that are roughly 50% identical at the amino acid level. Read More

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January 2021

Mapping the Mitochondrial Regulation of Epigenetic Modifications in Association With Carcinogenic and Noncarcinogenic Polycyclic Aromatic Hydrocarbon Exposure.

Int J Toxicol 2020 Sep/Oct;39(5):465-476. Epub 2020 Jun 26.

Department of Molecular Biology, 275313ICMR-National Institute for Research in Environmental Health, Bhopal, India.

Polycyclic aromatic hydrocarbons (PAHs) refer to a ubiquitous group of anthropogenic air pollutants that are generated through incomplete carbon combustion. Although the immunotoxic nature of PAHs has been previously reported, the underlying molecular mechanisms of this effect are not fully understood. In the present study, we investigated the mitochondrial-mediated epigenetic regulation of 2 PAHs, carcinogenic (benzo[a]pyrene; BaP) and noncarcinogenic (anthracene [ANT]), in peripheral lymphocytes. Read More

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KDM3A/Ets1/MCAM axis promotes growth and metastatic properties in Rhabdomyosarcoma.

Genes Cancer 2020 ;11(1-2):53-65

Department of Pathology, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.

Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy of childhood. RMS exists as two major disease subtypes, with oncofusion-positive RMS (FP-RMS) typically carrying a worse prognosis than oncofusion-negative RMS (FN-RMS), in part due to higher propensity for metastasis. Epigenetic mechanisms have recently emerged as critical players in the pathogenesis of pediatric cancers, as well as potential new therapeutic vulnerabilities. Read More

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January 2020

Lysine demethylase KDM3A regulates nanophotonic hyperthermia resistance generated by 2D silicene in breast cancer.

Biomaterials 2020 10 10;255:120181. Epub 2020 Jun 10.

Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. Electronic address:

Breast cancer (BC) is the most common malignant disease affecting women's health worldwide. The benefits from conventional therapeutic modalities are severely limited. An increasing number of promising photothermal materials have been recently developed and introduced into the therapeutic regimens of BC, but the underlying biological mechanism remains unclear. Read More

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October 2020

p300-Mediated Acetylation of Histone Demethylase JMJD1A Prevents Its Degradation by Ubiquitin Ligase STUB1 and Enhances Its Activity in Prostate Cancer.

Cancer Res 2020 08 10;80(15):3074-3087. Epub 2020 Jun 10.

Department of Biochemistry and Molecular Biology, University of Maryland, Baltimore, Maryland.

The androgen receptor (AR) pathway plays a central role in the development of castration-resistant prostate cancer (CRPC). The histone demethylase JMJD1A has been shown to regulate activities of AR and c-Myc transcription factors and promote prostate cancer progression. Here, we report that JMJD1A protein stability is controlled by the ubiquitin ligase STUB1. Read More

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Brahma Related Gene 1 (Brg1) Regulates Cellular Cholesterol Synthesis by Acting as a Co-factor for SREBP2.

Front Cell Dev Biol 2020 15;8:259. Epub 2020 May 15.

Key Laboratory of Targeted Intervention of Cardiovascular Disease and Collaborative Innovation Center for Cardiovascular Translational Medicine, Department of Pathophysiology, Nanjing Medical University, Nanjing, China.

Hepatocyte is a hub for cholesterol metabolism. Augmented synthesis of cholesterol in the liver is associated with hypercholesterolemia and contributes to the pathogenesis of a host of cardiovascular and metabolic diseases. Sterol response element binding protein 2 (SREBP2) regulates hepatic cholesterol metabolism by activating the transcription of rate-limiting enzymes in the cholesterol biosynthesis pathway. Read More

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