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ANKRD9 is associated with tumor suppression as a substrate receptor subunit of ubiquitin ligase
Lee, Yejin,Lim, Byungho,Lee, Seon Woo,Lee, Woo Rin,Kim, Yong-In,Kim, Minhyeok,Ju, Hyoungseok,Kim, Mi Young,Kang, Suk-Jo,Song, Ji-Joon,Lee, J. Eugene,Kang, Changwon Elsevier 2018 Biochimica et biophysica acta. Molecular basis of Vol.1864 No.10
<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Human <I>ANKRD9</I> (ankyrin repeat domain 9) expression is altered in some cancers.</P> <P><B>Methods</B></P> <P>We tested genetic association of ANKRD9 with gastric cancer susceptibility and examined functional association of ANKRD9 with altered proliferation of MKN45 gastric cancer cells. We then identified ANKRD9-binding partners in HEK 293 embryonic kidney cells using quantitative proteomics, western blotting and complex reconstitution assays. We finally demonstrated ANKRD9's role of recognizing substrates for ubiquitination using in vitro ubiquitylation assay.</P> <P><B>Results</B></P> <P> <I>ANKRD9</I> is associated with cancer susceptibility in a comparison of single-nucleotide polymorphisms between 1092 gastric cancer patients and 1206 healthy controls. ANKRD9 depletion accelerates tumor progression by increasing cellular proliferation, piling up, and anchorage-independent growth of MKN45 cells. We discovered that ANKRD9 is a ubiquitin ligase substrate receptor subunit and has an anti-proliferative activity. ANKRD9 associates with CUL5 (not CUL2), ELOB, ELOC, and presumably RNF7 subunits, which together assemble into a cullin-RING superfamily E3 ligase complex. ANKRD9 belongs to the ASB family of proteins, which are characterized by the presence of ankyrin repeats and a SOCS box. In addition to its interactions with the other E3 ligase subunits, ANKRD9 interacts with two isoforms of inosine monophosphate dehydrogenase (IMPDH). These IMPDH isoforms are cognate substrates of the ANKRD9-containing E3 enzyme, which ubiquitinates them for proteasomal degradation. Their ubiquitination and turnover require the presence of ANKRD9.</P> <P><B>Conclusion</B></P> <P>ANKRD9, a previously unidentified E3 substrate receptor subunit, functions in tumor suppression by recognizing the oncoprotein IMPDH isoforms for E3 ubiquitination and proteasomal degradation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Human <I>ANKRD9</I> is genetically associated with gastric cancer susceptibility. </LI> <LI> ANKRD9 protein activity is functionally associated with tumor suppression. </LI> <LI> ANKRD9 is a substrate receptor subunit of CUL5-based ubiquitin ligase E3 complex. </LI> <LI> E3 with ANKRD9 ubiquitinates substrate proteins for proteasomal degradation. </LI> <LI> Two isoforms of oncoprotein IMP dehydrogenase are cognate substrates of ANKRD9. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Minhyeok Lee,Ji Hye Kim,정인범,Ji Woong Son,Moon Jun Na,권선중 대한중환자의학회 2019 Acute and Critical Care Vol.34 No.1
Background:Use of a high-flow nasal cannula (HFNC) reduced postextubation respiratory failure (PERF) and reintubation rate compared to use of a low-flow oxygen system (LFOS) in low-risk patients. However, no obvious conclusion was reached for high-risk patients. Here, we sought to present the current status of HFNC use as adjunctive oxygen therapy in a clinical setting and to elucidate the nature of the protective effect following extubation. Methods:The medical records of 855 patients who were admitted to the intensive care unit of single university hospital during a period of 5.5 years were analyzed retrospectively, with only 118 patients ultimately included in the present research. The baseline characteristics of these patients and the occurrence of PERF and reintubation along with physiologic changes were analyzed. Results:Eighty-four patients underwent HFNC, and the remaining 34 patients underwent conventional LFOS after extubation. Physicians preferred HFNC to LFOS in the face of highrisk features including old age, neurologic disease, moderate to severe chronic obstructive pulmonary disease, a long duration of mechanical ventilation, low baseline arterial partial pressure of oxygen to fraction of inspired oxygen ratio, and a high baseline alveolar–arterial oxygen difference. The reintubation rate at 72 hours after extubation was not different (9.5% vs. 8.8%; P=1.000). Hypoxic respiratory failure was slightly higher in the nonreintubation group than in the reintubation group (31.9% vs. 6.7%; P=0.058). Regarding physiologic effects, heart rate was only stabilized after 24 hours of extubation in the HFNC group. Conclusions:No difference was found in the occurrence of PERF and reintubation between both groups. It is worth noting that similar PERF and reintubation ratios were shown in the HFNC group in those with certain exacerbating risk factors versus not. Caution is needed regarding delayed reintubation in the HFNC group.
HELLP syndrome in a pregnant patient with Gitelman syndrome
( Minhyeok Lee ),( Dong-il Kim ),( Kyung-ho Lee ),( Jun-hyun Byun ),( Jiyong Hwang ),( Won-min Hwang ),( Sung-ro Yun ),( Se-hee Yoon ) 대한신장학회 2017 Kidney Research and Clinical Practice Vol.36 No.1
Gitelman syndrome is characterized by hypokalemia, metabolic alkalosis, hypocalciuria, and hypomagnesemia. The clinical course of Gitelman syndrome in pregnant women remains unclear, but it is thought to be benign. We report here the first Korean case of atypical eclampsia in a 31-year-old who was diagnosed with Gitelman syndrome incidentally during an antenatal screening test. The patient did well during pregnancy despite significant hypokalemia. At 33 weeks` gestation, the patient exhibited eclampsia, hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, and renal insufficiency without significant hypertension or proteinuria. We explain this unusual clinical course through a review of the relevant literature.
A Comparison of Two-Stage Approaches Based on Penalized Regression for Estimating Gene Networks
Lee, Minhyeok,Seok, Junhee,Tae, Donghyun,Zhong, Hua,Han, Sung Won Mary Ann Liebert 2017 Journal of computational biology Vol.24 No.7
<P>Graphical models are commonly used for illustrating gene networks. However, estimating directed networks are generally challenging because of the limited sample size compared with the dimensionality of an experiment. Many previous studies have provided insight into the problem, and recently, two-stage approaches have shown significant improvements for estimating directed acyclic graphs. These two-stage approaches find neighborhoods in the first stage and determine the directions of the edges in the second stage. However, although numerous methods to find neighborhoods and determine directions exist, the most appropriate method to use with two-stage approaches has not been evaluated. Therefore, we compared such methods through extensive simulations to select effective methods for the first and second stages. Results show that adaptive lasso is the most effective for both stages in most cases. In addition, we compared methods to handle asymmetric entries to estimate an undirected network. Some previous studies indicate that the method used to handle asymmetric entries does not affect performance significantly; however, we found that the selection of the handling method for such edges is a significant factor for finding neighborhoods when using adaptive lasso.</P>
Enhanced Charge Injection in Pentacene Field‐Effect Transistors with Graphene Electrodes
Lee, Sangchul,Jo, Gunho,Kang, Seok‐,Ju,Wang, Gunuk,Choe, Minhyeok,Park, Woojin,Kim, Dong‐,Yu,Kahng, Yung Ho,Lee, Takhee Wiley - VCH Verlag GmbH & Co. KGaA 2011 Advanced Materials Vol. No.
<P><B>Pentacene organic field‐effect transistors</B> with multilayer graphene electrodes exhibit a lower contact resistance and lower charge‐injection barrier height than those with conventional Au electrodes. This enhancement in performance is related to the favorable dipole layer formation at the graphene/pentacene interface. </P>
( Minhyeok Lee ),( Ji Woong Son ),( Chang Ryul Park ),( Daeun Kang ),( Su Yel Lee ),( Se Jin Park ),( Wan Jin Hwang ),( Gwan Woo Ku ),( Seong Lan Yu ),( In Beom Jeong ),( Sun Jung Kwon ),( Jaeku Kang 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.-
Purpose Cancer stem cells (CSCs) identified in lung cancer exhibit resistance to chemotherapy, radiotherapy, and targeted therapy. Therefore, a technology to control of CSCs is needed to overcome such resistance to cancer therapy. Various evidences about the association between epithelial-mesenchymal transition related transcriptomic alteration and acquisition of CSC phenotype have been proposed recently. In our previous research, down-regulated miR-26a-5p is closely related to mesenchymal-like lung cancer cell lines. These findings suggest that miR-26a-5p might be involved in lung cancer stemness. Methods RNA polymerase III subunit G (POLR3G) was selected as a candidate target of miR-26a-5p related to cancer stemness. its quantitative relationship was investigated by polymerase chain reaction, western blot after transfection of miR-26a-5p. luciferase assay were done for investigating the direct regulation of miR-26a-5p on POLR3G expression. After transfection of miR-26a-5p, colony formation assay and sphere formation assay were performed to evaluate the effect on cancer stemness. By treating cancer cell by miR-26a-5p and paclitaxel, cell viability was checked by 3-(4,5-dimethylthiazol-2-yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and Muse cell analyzer. Expression level of each gene and its impact on survival were revealed by the cancer genome atlas pancancer database. Results miR-26a-5p regulated the expression of POLR3G directly. Overexpression of miR-26a-5p induced down regulation of POLR3G and a marked reduction of colony formation and sphere formation. Co-treatment of miR-26a-5p with paclitaxel decreased cell growth, suggesting that miR-26a-5p might play a role as a chemotherapy sensitizer. In the cancer genome atlas data, downregulated miR-26a-5p and up-regulated POLR3G were shown compared to adjacent normal tissue. High miR-26a-5p and low POLR3G expression were also related to higher survival rate of patients with lung adenocarcinoma. Conclusions Overexpression of miR-26a-5p can suppress lung cancer stemness and make cancer cell become sensitive to chemotherapy. This finding provides a novel insight into a potential lung cancer treatment by regulating stemness.