KyoungHyun Kim, PhD
University of Arkansas for Medical Sciences
College of Medicine
Phamacology & Toxicology
Cancer Research Interest
- Disease Site Focus: GI, Breast
- Research Focus Area: Carcinogenesis, Prevention, Treatment, Informatics
- Type of Research: Basic, Translational
- Research Keywords: Nuclear receptor, noncoding RNA, epigenetics, epitranscriptomic, liver, Pancreas
- Research Interest Statement: Our lab has focused on the role of nuclear receptor NR2E3 as a key epigenetic regulator that prevents chronic liver injury and cancer development. Approximately 14% of all U.S. FDA-approved small-molecule drug targets are nuclear receptors. Nuclear receptor subfamily 2 group E member 3 (NR2E3) plays a crucial role in retinal development. Out previous reports for the first time showed that NR2E3 is essential for maintaining the basal expression of estrogen receptor α (ER) and is a significantly good prognostic marker for relapse-free survival in patients with breast cancer. NR2E3 formed an active transcriptional complex with specificity protein 1 (Sp1) transcription factor and maintained the basal expression of aryl hydrocarbon receptor (AHR) by preventing histone demethylase LSD1-mediated epigenetic reprogramming. We further elucidated the novel molecular link between the NR2E3 and tumor suppressive p53 signaling pathways. NR2E3 ablation in both in vivo and in vitro induces epigenetic repression of DINO, a long noncoding RNA essential for p53 activation. This disruption of the NR2E3-DINO–p53 signaling axis leads to more severe liver injuries. Our long-term goal is to provide scientific knowledge to help develop NR2E3 as a molecular target in liver injury and cancer development. Long noncoding (lnc) RNAs are transcripts more than 200 base-pair in length which is not translated into proteins. LncRNAs regulate gene expression at transcriptional, RNA processing, translational, and post‐translational levels through interaction with nucleic acids and proteins, controlling cell proliferation, differentiation, apoptosis, and senescence. We previously reported that environmental toxicant-activated AHR increased the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in pancreatic cancer cells and pancreatic tissues. The Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is activated by various environmental toxicants, phytochemicals, and microbiome metabolites. The MALAT1 is a long noncoding (lnc) RNA which interacts with Enhancer of Zeste 2 (EZH2), a histone methyltransferase and this MALAT1-EZH2 interaction increased its epigenetic silencing activity that regulates pancreatic injury and carcinogenesis. We currently focused on elucidating epigenetic roles of AHR-regulated lncRNAs in the environmental toxicant-induced pancreatic injury and pancreatic cancer development.
- Email Address: KKIM@UAMS.EDU
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- McDermott A, Kim K, Kasper S, [et al.]. The androgen receptor inhibits transcription of GPER1 by preventing Sp1 and Sp3 from binding to the promoters in prostate cancer cells. Oncotarget. 2022 13:46-60. PMID: 35018219. PMCID: PMC8741193.
- Christov PP, Richie-Jannetta R, Kingsley PJ, [et al., including Kim K]. Site-Specific Synthesis of Oligonucleotides Containing 6-Oxo-M1dG, the Genomic Metabolite of M1dG, and Liquid Chromatography-Tandem Mass Spectrometry Analysis of Its In Vitro Bypass by Human Polymerase ?. Chemical research in toxicology. 2021. PMID: 34860508.
- Cho SG, Ko SG, Ahrmad SA, [et al., including Kim K]. Regulation of a long noncoding RNA MALAT1 by aryl hydrocarbon receptor in pancreatic cancer cells and tissues. Biochemical and biophysical research communications. 2020 532(4):563-569. PMID: 32900487. PMCID: PMC7572814.
- Khanal T, Leung YK, Jiang W, [et al., including Kim K]. NR2E3 is a key component in p53 activation by regulating a long noncoding RNA DINO in acute liver injuries. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2019 33(7):8335-8348. PMID: 30991008. PMCID: PMC6593879.
- Lee T, Christov PP, Shaw S, [et al., including Kim K]. Discovery of Potent Myeloid Cell Leukemia-1 (Mcl-1) Inhibitors That Demonstrate in Vivo Activity in Mouse Xenograft Models of Human Cancer. Journal of medicinal chemistry. 2019 62(8):3971-3988. PMID: 30929420.
- Pitch MA, Kim KH, Manning T, [et al.]. A diagnostically challenging case of CD8+ primary cutaneous gamma/delta T-cell lymphoma. Dermatology online journal. 2017 23(11). PMID: 29447636.
- St Louis AM, Kim K, Browne ML, [et al.]. Prevalence trends of selected major birth defects: A multi-state population-based retrospective study, United States, 1999 to 2007. Birth defects research. 2017 109(18):1442-1450. PMID: 28905502.
- Khanal T, Choi K, Leung YK, [et al., including Kim K]. Loss of NR2E3 represses AHR by LSD1 reprogramming, is associated with poor prognosis in liver cancer. Scientific reports. 2017 7(1):10662. PMID: 28878246. PMCID: PMC5587550.
- Kern M, Kim KH, Johnson G, [et al.]. Dermatitis herpetiformis presenting as pseudovasculitis. JAAD case reports. 2017 3(5):444-447. PMID: 28971130. PMCID: PMC5602830.
- Wang X, Maruvada R, Morris AJ, [et al., including Kim KS]. Sphingosine 1-Phosphate Activation of EGFR As a Novel Target for Meningitic Escherichia coli Penetration of the Blood-Brain Barrier. PLoS pathogens. 2016 12(10):e1005926. PMID: 27711202. PMCID: PMC5053521.