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( Ok-seon Kwon ),( Soo-jung Kwon ),( Jin Sang Kim ),( Gunbong Lee ),( Han-joo Maeng ),( Jeongmi Lee ),( Gwi Seo Hwang ),( Hyuk-jin Cha ),( Kwang-hoon Chun ) 한국응용약물학회 2018 Biomolecules & Therapeutics(구 응용약물학회지) Vol.26 No.3
Melanin is a pigment produced from tyrosine in melanocytes. Although melanin has a protective role against UVB radiationinduced damage, it is also associated with the development of melanoma and darker skin tone. Tyrosinase is a key enzyme in melanin synthesis, which regulates the rate-limiting step during conversion of tyrosine into DOPA and dopaquinone. To develop effective RNA interference therapeutics, we designed a melanin siRNA pool by applying multiple prediction programs to reduce human tyrosinase levels. First, 272 siRNAs passed the target accessibility evaluation using the RNAxs program. Then we selected 34 siRNA sequences with ΔG ≥-34.6 kcal/mol, i-Score value ≥65, and siRNA scales score ≤30. siRNAs were designed as 19-bp RNA duplexes with an asymmetric 3’ overhang at the 3’ end of the antisense strand. We tested if these siRNAs effectively reduced tyrosinase gene expression using qRT-PCR and found that 17 siRNA sequences were more effective than commercially available siRNA. Three siRNAs further tested showed an effective visual color change in MNT-1 human cells without cytotoxic effects, indicating these sequences are anti-melanogenic. Our study revealed that human tyrosinase siRNAs could be efficiently designed using multiple prediction algorithms.
GalNAc-T14promotes metastasis through Wnt dependent HOXB9 expression in lung adenocarcinoma
Ok-Seon Kwon,Jhingook Kim,Hyuk-Jin Cha 한국당과학회 2016 한국당과학회 학술대회 Vol.2016 No.01
While metastasis, the main cause of lung cancer-related death, has been extensively studied, the underlying molecular mechanism remains unclear. A previous clinicogenomic study revealed that expression of N-acetylgalactosaminyltransferase (GalNAc-T14), is highly correlated with recurrence-free survival in those with non-small cell lung cancer (NSCLC). However, the underlying molecular mechanism(s) has not been determined. Here we showed that GalNAc-T14 expression was closely associated with the invasive phenotype. Microarray and biochemical analyses revealed that HOXB9 , the expression of which was regulated in a GalNAc-T14-dependent manner, played an important role in metastasis. GalNAc-T14 increased the sensitivity of the WNT response and increased the stability of the b-catenin protein, leading to induced expression of HOXB9 and acquisition of an invasive phenotype. Pharmacological inhibition of b-catenin in GalNAc-T14-expressing cancer cells suppressed HOXB9 expression and suppressed invasion. A meta-analysis of clinical genomics data revealed that expression of GalNAc-T14 or HOXB9 was strongly correlated with recurrence-free survival and hazard risk, suggesting that targeting b-catenin within the GalNAc-T14/WNT/HOXB9 axis may be a novel therapeutic approach to inhibit metastasis in NSCLC.
( Ok-seon Kwon ),( Min-joon Han ),( Hyuk-jin Cha ) 생화학분자생물학회(구 한국생화학분자생물학회) 2017 BMB Reports Vol.50 No.9
Primed human pluripotent stem cells (hPSCs) are highly dependent on glycolysis rather than oxidative phosphorylation, which is similar to the metabolic switch that occurs in cancer cells. However, the molecular mechanisms that underlie this metabolic reprogramming in hPSCs and its relevance to pluripotency remain unclear. Cha et al. (2017) recently revealed that downregulation of SIRT2 by miR-200c enhances acetylation of glycolytic enzymes and glycolysis, which in turn facilitates cellular reprogramming, suggesting that SIRT2 is a key enzyme linking the metabolic switch and pluripotency in hPSCs. [BMB Reports: Perspective 2017; 50(9): 435-436]
Ok, Seon-Yeong,Cho, Kwon-Koo,Kim, Ki-Won,Ryu, Kwang-Sun Royal Swedish Academy of Sciences 2010 Physica scripta Vol.2010 No.t139
<P>Well-ordered TiO<SUB>2</SUB> nanotube arrays were fabricated by the potentiostatic anodic oxidation method using pure Ti foil as a working electrode and ethylene glycol solution as an electrolyte with the small addition of NH<SUB>4</SUB>F and H<SUB>2</SUB>O. The influence of anodization temperature and time on the morphology and formation of TiO<SUB>2</SUB> nanotube arrays was examined. The TiO<SUB>2</SUB> nanotube arrays were applied as a photoelectrode to dye-sensitized solar cells. Regardless of anodizing temperature and time, the average diameter and wall thickness of TiO<SUB>2</SUB> nanotube arrays show a similar value, whereas the length increases with decreasing reaction temperature. The conversion efficiency is very low, which is due to a morphology breaking of the TiO<SUB>2</SUB> nanotube arrays in the manufacturing process of a photoelectrode.</P>
Kwon, Ok-Seon,Kwon, Soo-Jung,Kim, Jin Sang,Lee, Gunbong,Maeng, Han-Joo,Lee, Jeongmi,Hwang, Gwi Seo,Cha, Hyuk-Jin,Chun, Kwang-Hoon The Korean Society of Applied Pharmacology 2018 Biomolecules & Therapeutics(구 응용약물학회지) Vol.26 No.3
Melanin is a pigment produced from tyrosine in melanocytes. Although melanin has a protective role against UVB radiation-induced damage, it is also associated with the development of melanoma and darker skin tone. Tyrosinase is a key enzyme in melanin synthesis, which regulates the rate-limiting step during conversion of tyrosine into DOPA and dopaquinone. To develop effective RNA interference therapeutics, we designed a melanin siRNA pool by applying multiple prediction programs to reduce human tyrosinase levels. First, 272 siRNAs passed the target accessibility evaluation using the RNAxs program. Then we selected 34 siRNA sequences with ${\Delta}G{\geq}-34.6kcal/mol$, i-Score value ${\geq}65$, and siRNA scales score ${\leq}30$. siRNAs were designed as 19-bp RNA duplexes with an asymmetric 3' overhang at the 3' end of the antisense strand. We tested if these siRNAs effectively reduced tyrosinase gene expression using qRT-PCR and found that 17 siRNA sequences were more effective than commercially available siRNA. Three siRNAs further tested showed an effective visual color change in MNT-1 human cells without cytotoxic effects, indicating these sequences are anti-melanogenic. Our study revealed that human tyrosinase siRNAs could be efficiently designed using multiple prediction algorithms.