• Title/Summary/Keyword: SF3B4

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SF3B4 Depletion Retards the Growth of A549 Non-Small Cell Lung Cancer Cells via UBE4B-Mediated Regulation of p53/p21 and p27 Expression

  • Kim, Hyungmin;Lee, Jeehan;Jung, Soon-Young;Yun, Hye Hyeon;Ko, Jeong-Heon;Lee, Jeong-Hwa
    • Molecules and Cells
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    • v.45 no.10
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    • pp.718-728
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    • 2022
  • Splicing factor B subunit 4 (SF3B4), a component of the U2-pre-mRNA spliceosomal complex, contributes to tumorigenesis in several types of tumors. However, the oncogenic potential of SF3B4 in lung cancer has not yet been determined. The in vivo expression profiles of SF3B4 in non-small cell lung cancer (NSCLC) from publicly available data revealed a significant increase in SF3B4 expression in tumor tissues compared to that in normal tissues. The impact of SF3B4 deletion on the growth of NSCLC cells was determined using a siRNA strategy in A549 lung adenocarcinoma cells. SF3B4 silencing resulted in marked retardation of the A549 cell proliferation, accompanied by the accumulation of cells at the G0/G1 phase and increased expression of p27, p21, and p53. Double knockdown of SF3B4 and p53 resulted in the restoration of p21 expression and partial recovery of cell proliferation, indicating that the p53/p21 axis is involved, at least in part, in the SF3B4-mediated regulation of A549 cell proliferation. We also provided ubiquitination factor E4B (UBE4B) is essential for p53 accumulation after SF3B4 depletion based on followings. First, co-immunoprecipitation showed that SF3B4 interacts with UBE4B. Furthermore, UBE4B levels were decreased by SF3B4 depletion. UBE4B depletion, in turn, reproduced the outcome of SF3B4 depletion, including reduction of polyubiquitinated p53 levels, subsequent induction of p53/p21 and p27, and proliferation retardation. Collectively, our findings indicate the important role of SF3B4 in the regulation of A549 cell proliferation through the UBE4B/p53/p21 axis and p27, implicating the therapeutic strategies for NSCLC targeting SF3B4 and UBE4B.

SF3B4 as an early-stage diagnostic marker and driver of hepatocellular carcinoma

  • Shen, Qingyu;Nam, Suk Woo
    • BMB Reports
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    • v.51 no.2
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    • pp.57-58
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    • 2018
  • An accurate diagnostic marker for detecting early-stage hepatocellular carcinoma (eHCC) is clinically important, since early detection of HCC remarkably improves patient survival. From the integrative analysis of the transcriptome and clinicopathologic data of human multi-stage HCC tissues, we were able to identify barrier-to-autointegration factor 1 (BANF1), procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3) and splicing factor 3b subunit 4 (SF3B4) as early HCC biomarkers which could be detected in precancerous lesions of HCC, with superior capabilities to diagnose eHCC compared to the currently popular HCC diagnostic biomarkers: GPC3, GS, and HSP70. We then showed that SF3B4 knockdown caused G1/S cell cycle arrest by recovering $p27^{kip1}$ and simultaneously suppressing cyclins, and CDKs in liver cancer cells. Notably, we demonstrated that aberrant SF3B4 overexpression altered the progress of splicing progress of the tumor suppressor gene, kruppel like factor 4 (KLF4), and resulted in non-functional skipped exon transcripts. This contributes to liver tumorigenesis via transcriptional inactivation of $p27^{kip1}$ and simultaneous activation of Slug genes. Our results suggest that SF3B4 indicates early-stage HCC in precancerous lesions, and also functions as an early-stage driver in the development of liver cancer.

Self-renewal and circulating capacities of metastatic hepatocarcinoma cells required for collaboration between TM4SF5 and CD44

  • Lee, Doohyung;Lee, Jung Weon
    • BMB Reports
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    • v.48 no.3
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    • pp.127-128
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    • 2015
  • Tumor metastasis involves circulating and tumor-initiating capacities of metastatic cancer cells. Hepatic TM4SF5 promotes EMT for malignant growth and migration. Hepatocellular carcinoma (HCC) biomarkers remain unexplored for metastatic potential throughout metastasis. Here, novel TM4SF5/CD44 interaction-mediated self-renewal and circulating tumor cell (CTC) capacities were mechanistically explored. TM4SF5-dependent sphere growth was correlated with $CD133^+$, $CD24^-$, ALDH activity, and a physical association between CD44 and TM4SF5. The TM4SF5/CD44 interaction activated c-Src/STAT3/ Twist1/ B mi1 signaling for spheroid formation, while disturbing the interaction, expression, or activity of any component in this signaling pathway inhibited spheroid formation. In serial xenografts of less than 5,000 cells/injection, TM4SF5-positive tumors exhibited locally-increased CD44 expression, suggesting tumor cell differentiation. TM4SF5-positive cells were identified circulating in blood 4 to 6 weeks after orthotopic liver-injection. Anti-TM4SF reagents blocked their metastasis to distal intestinal organs. Altogether, our results provide evidence that TM4SF5 promotes self-renewal and CTC properties supported by $CD133^+/TM4SF5^+/CD44^+^{(TM4SF5-bound)}/ALDH^+/CD24^-$ markers during HCC metastasis.

A Study on Characteristic of Autogenous Shrinkage of High Strength Concrete (고강도 콘크리트의 자기수축 특성에 관한 연구)

  • Lee, Young-Jae
    • Journal of the Korean Society of Industry Convergence
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    • v.16 no.1
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    • pp.1-8
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    • 2013
  • In case that W/B is 20%, 30%, 40% respectively, the effects of additive and shrinkage reducing agent on the autogenous shrinkage for high strengthen concrete through the substitution of FA and SF analysis were obtained as following conclusions. When the ratio of FA increased, the compressive strength of high strengthen concrete is decreased in the early times. As the ratio of SF increase, the compressive strength also increased. Comparing with PC(Portland Cement) for 7 days curing, the strength is 13.8% of FA10 + SR0.5 and 19.2% of FA15 + SR0.5 decreased when W/B is 20%, and 6.1% of SF7.5 + SR0.5, 4.8% of SF15 + SR0.5, the strength are increased. In case that W/B is 30%, 13.1% of FA10 + SR0.5 19.1% of FA15 + SR0.5 the strength is decreased and 4.1% of SF 7.5 + SR0.5, 7.2% of SF15 + SR0.5 the strength are increased. In case of W/B 40%, 4.3% of FA10 + SR0.5, and 8.7% of FA15 + SR0.5, the strength is decreased and 3.3% of SF7.5 + SR0.5, 6.3% SF15 + SR0.5 the strength is increased. When the ratio of SR is 0.5%, autogenous shrinkage strain of OPC concrete appeared $-417{\times}10-6$ in 56days curing, the shrinkage strain is decreased 23.7%. The reducing effects of autogenous shrinkage when the mineral and shrinkage agent are used are the same as ones when only shrinkage agent used.

Implementation of WLAN Baseband Processor Based on Space-Frequency OFDM Transmit Diversity Scheme (공간-주파수 OFDM 전송 다이버시티 기법 기반 무선 LAN 기저대역 프로세서의 구현)

  • Jung Yunho;Noh Seungpyo;Yoon Hongil;Kim Jaeseok
    • Journal of the Institute of Electronics Engineers of Korea SD
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    • v.42 no.5 s.335
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    • pp.55-62
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    • 2005
  • In this paper, we propose an efficient symbol detection algorithm for space-frequency OFDM (SF-OFDM) transmit diversity scheme and present the implementation results of the SF-OFDM WLAN baseband processor with the proposed algorithm. When the number of sub-carriers in SF-OFDM scheme is small, the interference between adjacent sub-carriers may be generated. The proposed algorithm eliminates this interference in a parallel manner and obtains a considerable performance improvement over the conventional detection algorithm. The bit error rate (BER) performance of the proposed detection algorithm is evaluated by the simulation. In the case of 2 transmit and 2 receive antennas, at $BER=10^{-4}$ the proposed algorithm obtains about 3 dB gain over the conventional detection algorithm. The packet error rate (PER), link throughput, and coverage performance of the SF-OFDM WLAN with the proposed detection algorithm are also estimated. For the target throughput at $80\%$ of the peak data rate, the SF-OFDM WLAN achieves the average SNR gain of about 5.95 dB and the average coverage gain of 3.98 meter. The SF-OFDM WLAN baseband processor with the proposed algorithm was designed in a hardware description language and synthesized to gate-level circuits using 0.18um 1.8V CMOS standard cell library. With the division-free architecture, the total logic gate count for the processor is 945K. The real-time operation is verified and evaluated using a FPGA test system.

Domain Expression of ErmSF, MLS (macrolide-lincosamide-streptogramin B) Antibiotic Resistance Factor Protein (MLS (macrolide-lincosamide-streptogramin B) 항생제 내성인자 단백질인 ErmSF의 domain발현)

  • 진형종
    • Korean Journal of Microbiology
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    • v.37 no.4
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    • pp.245-252
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    • 2001
  • Erm proteins, MLS (macrolide-lincosamide-streptogramin B) resistance factor proteins, show high degree of amino acid sequence homology and comprise of a group of structurally homologous N-methyltransferases. On the basis of the recently determined structures of ErmC` and ErmAM, ErmSF was divided into two domains, N-terminal end catalytic domain and C-terminal end substrate binding domain and attempted to overexpress catalytic domain in E. coli using various pET expression systems. Three DNA fragments were used to express the catalytic domain: DNA fragment 1 encoding Met 1 through Glu 186, DNA fragment 2 encoding Arg 60 to Glu 186 and DNA fragment 3 encoding Arg 60 through Arg 240. Among the pET expression vectors used, pET 19b successfully expressed the DNA fragment 3 and pET23b succeeded in expression of DNA fragment 1 and 2. But the overexpressed catalytic domains existed as inclusion body, a insoluble aggregate. To assist the soluble expression of ErmSF catalytic domains, Coexpression of chaperone GroESL or Thioredoxin and lowering the incubation temperature to $22^{\circ}C$ were attempted, as did in the soluble expression of the whole ErmSF protein. Both strategies did not seem to be helpful. Solubilization with guanidine-HCl and renaturation with gradual removal of denaturant and partial digestion of overexpressed whole ErmSF protein (expressed to the level of 126 mg/ι culture as a soluble protein) with proteinase K, nonspecific proteinase are under way.

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Efficient Symbol Detection Algorithm for Space-frequency OFDM Transmit Diversity Scheme (공간-주파수 OFDM 전송 다이버시티 기법을 위한 효율적인 심볼 검출 알고리즘)

  • Jung Yun ho;Kim Jae seok
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.30 no.4C
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    • pp.283-289
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    • 2005
  • In this paper, we propose two efficient symbol detection algorithms for space-frequency OFDM (SF-OFDM) transmit diversity scheme. When the number of sub-carriers in SF-OFBM scheme is small, the interference between adjacent sub-carriers may be generated. The proposed algorithms eliminate this interference in a parallel or sequential manlier and achieve a considerable performance improvement over the conventional detection algorithm. The bit error rate (BER) performance of the proposed detection algorithms is evaluated by the simulation. In the case of 2 transmit and 2 receive antennas, at $BER=10^{-4}$ the proposed algorithms achieve the gain improvement of about 3 dB. The symbol detectors with the proposed algorithms are designed in a hardware description language and synthesized to gate-level circuits with the $0.18{\mu}m$ 1.8V CMOS standard cell library. With the division-free architecture, the proposed SF-OFDM-PIC and SF-OFDM-SIC symbol detectors can be implemented using 140k and 129k logic gates, respectively.

Preparation of Sulfobetaine Chitosan, Silk Blended Films, and Their Properties (설포베타인 키토산의 실크 블렌드 필름의 제조 및 그들의 성질)

  • Koo, Ja-Sung;Cha, Jae-Ryung;Oh, Se-Heang;Gong, Myoung-Seon
    • Polymer(Korea)
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    • v.38 no.1
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    • pp.54-61
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    • 2014
  • Water-soluble sulfobetaine chitosan (SCs) was prepared for a blending film with Bombyx mori silk fibroin (SF) by reacting chitosan with 1,3-propanesultone. A series of SF/SCs blended films were successfully prepared by mixing aqueous solutions of B. mori SF and SCs. The SF/SCs blended films were examined through spectroscopic and thermal analysis to determine the morphological changes of SF in the SCs. The effects of the SF/SCs blend ratios on physical and mechanical properties were investigated to discover the feasibility of using these films as biomedical materials such as artificial skin and wound dressing. X-ray analysis showed good compatibility between the two biopolymers. The in vitro degradation behavior of the SF/SCs blended films was systematically investigated for up to 8 weeks in phosphate buffered saline solution at $37^{\circ}C$ and showed a mass loss of 46.4% after 8 weeks. All films showed no cytotoxicity by MC3T3-E1 assay. After 3 days of culture, the relative cell number on all the SF/SCs films was slightly lower than that of an optimized tissue culture plastic.

A Study on the Dielectric Strength in Section of Winding in SF6 Gas Transformer ($SF_6$ 가스절연변압기에서 권선의 섹션에 대한 절연내력 연구)

  • Heo, U-Haeng;Ha, Yeong-Sik;Hong, Jeong-Pyo;Kim, Gyu-Tak
    • The Transactions of the Korean Institute of Electrical Engineers B
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    • v.49 no.3
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    • pp.152-158
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    • 2000
  • This paper deal with the experimental discussion about the impulse and AC dielectric strength of SF6 gas insulated transformer. Test sample is measured the dielectric breakdown voltage about modeling of the first and second section which is the weakest for surge voltage. The AC breakdown voltage is appeared 1.4 times than impulse breakdown voltage, so we can estimate that the impulse breakdown voltage is severe to AC breakdown voltage, and when the impulse is applied, in case of lmm tapping with Nomex paper, the characteristics of dielectric breakdown voltage is same to that in oil immersed transformer when SF6 gas pressure is 2.2kg/$cm^2$G.

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Characterization and evaluation of liver fibrosis grade in patients with chronic hepatitis B virus infection and normal transaminases

  • Cristina, San Juan Lopez;Marta, Casado Martin;Mercedes, Gonzalez Sanchez;Almudena, Porcel Martin;Alvaro, Hernandez Martinez;Luis, Vega Saenz Jose;Tesifon, Parron Carreno
    • Clinical and Molecular Hepatology
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    • v.24 no.4
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    • pp.384-391
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    • 2018
  • Backgrounds/Aims: The objective of our study was to determine the epidemiological, laboratory, and serological characteristics of patients with chronic hepatitis B virus (HBV) infection and normal transaminases. The study also aimed to evaluate liver damage by measuring the liver fibrosis (LF) grade and to identify possible factors associated with the presence of fibrosis. Methods: A retrospective observational study was conducted in patients with chronic HBV infection and classified as inactive carriers or immune-tolerant. Epidemiological variables of age, sex, immigrant, alcohol consumption, and body mass index (BMI), as well as virological variables (HBV DNA) and transaminase level were collected throughout the follow-up. The LF grade was evaluated by transient elastography. The cutoff value for significant fibrosis (SF) was liver stiffness ${\geq}7.9kPa$. Results: A total of 214 patients were included in the analysis, and 62% of them had a BMI ${\geq}25kg/m^2$. During follow-up, 4% of patients showed transaminase elevation (<1.5 times normal). Most patients had a viral DNA level <2,000 IU/mL (83%). Data on LF were available in 160 patients; of these, 14% had SF, 9% F3, and 6% F4. The variables associated with the presence of SF were transaminase alteration during follow-up, as 23% of patients with SF had elevated transaminases versus 3% of patients without SF (P<0.005), and BMI, as the vast majority of patients with SF (88%) had a BMI ${\geq}25kg/m^2$ versus 56% of patients without SF (P<0.05). Conclusions: In patients with chronic HBV infection and normal transaminases, liver damage does not seem to be related to DNA levels, alcohol consumption, or immigrant status. SF seems to be associated with transaminase alteration during follow-up and elevated BMI. It is therefore recommended to measure LF grade with validated non-invasive methods in such patients.