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López-Cánovas Juan L.,Hermán-Sánchez Natalia,del Rio-Moreno Mercedes,Fuentes-Fayos Antonio C.,Lara-López Araceli,Sánchez-Frias Marina E.,Amado Víctor,Ciria Rubén,Briceño Javier,de la Mata Manuel,Casta 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Hepatocellular carcinoma (HCC) pathogenesis is associated with alterations in splicing machinery components (spliceosome and splicing factors) and aberrant expression of oncogenic splice variants. We aimed to analyze the expression and potential role of the spliceosome component PRPF8 (pre-mRNA processing factor 8) in HCC. PRPF8 expression (mRNA/protein) was analyzed in a retrospective cohort of HCC patients (n = 172 HCC and nontumor tissues) and validated in two in silico cohorts (TCGA and CPTAC). PRPF8 expression was silenced in liver cancer cell lines and in xenograft tumors to understand the functional and mechanistic consequences. In silico RNAseq and CLIPseq data were also analyzed. Our results indicate that PRPF8 is overexpressed in HCC and associated with increased tumor aggressiveness (patient survival, etc.), expression of HCC-related splice variants, and modulation of critical genes implicated in cancer-related pathways. PRPF8 silencing ameliorated aggressiveness in vitro and decreased tumor growth in vivo. Analysis of in silico CLIPseq data in HepG2 cells demonstrated that PRPF8 binds preferentially to exons of protein-coding genes, and RNAseq analysis showed that PRPF8 silencing alters splicing events in multiple genes. Integrated and in vitro analyses revealed that PRPF8 silencing modulates fibronectin (FN1) splicing, promoting the exclusion of exon 40.2, which is paramount for binding to integrins. Consistent with this finding, PRPF8 silencing reduced FAK/AKT phosphorylation and blunted stress fiber formation. Indeed, HepG2 and Hep3B cells exhibited a lower invasive capacity in membranes treated with conditioned medium from PRPF8-silenced cells compared to medium from scramble-treated cells. This study demonstrates that PRPF8 is overexpressed and associated with aggressiveness in HCC and plays important roles in hepatocarcinogenesis by altering FN1 splicing, FAK/AKT activation and stress fiber formation.
Serum Sclerostin in Hepatitis C Virus Infected Patients
E. González-Reimers,Javier López-Prieto,Ricardo Pelazas-González,M.Remedios Alemán-Valls,María José de la Vega-Prieto,Carlos Jorge-Ripper,M. Carmen Durán-Castellón,F Santolaria-Fernández 대한골대사학회 2014 대한골대사학회지 Vol.21 No.1
Background: Sclerostin inhibits osteoblast functions, differentiations, and survival rates. As an endogenous inhibitor of the Wnt/β-catenin pathway, the sclerostin should be re-lated to decreased bone masses, although several studies indicate opposite results. Inaddition, it may be related to insulin resistances and carbohydrate metabolisms, a rela-tion shared with other markers of bone metabolisms, such as osteocalcin. Hepatitis C vi-rus (HCV) infected patients may present osteoporosis, and frequently show liver steato-sis, which is a consequence of insulin resistance. The behaviour of sclerostin in these pa-tients is yet unknown. The aim of this work is to analyse the relationships between se-rum sclerostin and osteocalcin levels and bone mineral density (BMD), liver functions,the intensity of liver steatosis and biochemical markers of bone homeostasis and insulinresistance in HCV-infected patients. Methods: Forty HCV patients with 20 years of ageand gender-matching controls were included in this study and underwent bone densi-tometry. Serum sclerostin, osteocalcin, collagen telopeptide, adiponectin, leptin, insulin,resistin, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were determined. Liver fatwas histomorphometrically assessed. Results: Sclerostin levels were slightly higher inpatients than in controls, and were directly related to BMD at different parts of the skele-ton, also to the serum telopeptide, and to the liver steatosis and TNF-α. On the contrary,osteocalcin showed a significant direct relationship with serum adiponectin, and an in-verse one with IL-6. Conclusions: Serum sclerostin levels were within the normal rangein HCV patients, and correlated directly with BMD and serum telopeptide. In addition,the relationships of sclerostin and osteocalcin with variables associated with insulin re-sistance suggested the role of bones for intermediary metabolisms.
Chang Ihn Yang,E. L. Javier,Young Chan Cho,Kyu Seong Lee,Hong Yeol Kim,K. K. Jena,Young Tae Lee 한국육종학회 2007 한국육종학회지 Vol.39 No.2
This study was done to understand the G x E interaction of rice blast reaction for Japonica high quality rice varieties and to observe blast pattern for high quality varieties. Twenty one percent of the total sum of squares (SST) in blast reaction data of high quality Japonica varieties is attributed to genotype (G) by environment (E) interaction variation. This portion of blast response is higher than 8~12% of G x E effect in blast severity data obtained from various ecotypes of rice varieties. Blast response scores obtained from high quality Japonica varieties group were more severely affected by environment condition than mixed groups with Japonica and Indica varieties. Interaction Principal Component Analysis (IPCA) scores obtained from AMMI analysis for the leaf blast response implied variation of G x E interaction. Correlation analysis suggested that IPCA1 was associated with latitude, maximum mean temperature, precipitation and mean cloud amount. IPCA2 was associated with mean relative humidity, and IPCA3 was associated with precipitation and minimum relative humidity. Pattern analysis generated nine genotype clusters according to blast reaction over 11 regions. Collectively, the A, B, C, and D groups were susceptible to rice blast, where as the E, F, G, H, and I groups were relatively resistant to rice blast through multi-location blast nursery test. Relationship between the identified genes of high quality varieties and blast scores at each test site in the level of group could be analyzed based on the results from G x E Interaction analysis.
Chang Ihn Yang,E.L. Javier,Yong Jae Won,Sae Jun Yang,Hae Chune Choi,Young Boum Shin 韓國作物學會 2000 Korean journal of crop science Vol.45 No.5
Blast severity data of 39 rice varieties at 11 sites in Korea from 1997 to 1999 were analyzed using AMMI model and pattern analysis. Genotype x Environment (G~times E) interaction sum of squares (SS) accounted for 12 % of the total SS. Eight genotype groups and seven location groups were identified based on blast reaction pattern. The data obtained from over 21 sites with 44 test varieties from 1981 to 1996 were also considered. These were compared with the 1997-1999 data using the G~times E analysis results. Majority of the variability in the Korean Rice Blast Nursery (KRBN) were attributable to variations due to genotypes. Variations of G~times E interaction were maintained though test sites were reduced from 21 to 11 sites. Broadly compatible biological discriminative varieties identified were Nagdongbyeo and Akibare while broadly incompatible biological discriminative varieties identified were Hangangchalbyeo and Seogwangbyeo. Key sites for future evaluation work could be selected from location groups. Each location group should be represented by the site with the strongest interaction pattern. Blast responses in Cheolwon, Gyehwa, Suwon, Iksan, and Icheon showed different patterns from other locations.