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Experimental & Molecular Medicine

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https://www.readbyqxmd.com/read/29350680/effects-of-microrna-135a-on-the-epithelial-mesenchymal-transition-migration-and-invasion-of-bladder-cancer-cells-by-targeting-gsk3%C3%AE-through-the-wnt-%C3%AE-catenin-signaling-pathway
#1
Xia-Wa Mao, Jia-Quan Xiao, Zhong-Yi Li, Yi-Chun Zheng, Nan Zhang
This study investigated the effects of microRNA-135a (miR-135a) targeting of glycogen synthase kinase 3β (GSK3β) on the epithelial-mesenchymal transition (EMT), migration and invasion of bladder cancer (BC) cells by mediating the Wnt/β-catenin signaling pathway. BC and adjacent normal tissues were collected from 165 BC patients. Western blotting and quantitative real-time PCR were used to detect the expression of GSK3β, β-catenin, cyclinD1, E-cadherin, vimentin and miR-135a in BC tissues and cells. Cells were assigned to blank, negative control (NC), miR-135a mimics, miR-135a inhibitors, small interfering RNA (siRNA)-GSK3β or miR-135a inhibitors+siRNA-GSK3β groups...
January 19, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29350679/proangiogenic-functions-of-an-rgd-slay-containing-osteopontin-icosamer-peptide-in-huvecs-and-in-the-postischemic-brain
#2
Hahnbie Lee, Yin-Chuan Jin, Seung-Woo Kim, Il-Doo Kim, Hye-Kyung Lee, Ja-Kyeong Lee
Osteopontin (OPN) is a phosphorylated glycoprotein secreted into body fluids by various cell types. OPN contains arginine-glycine-aspartate (RGD) and serine-leucine-alanine-tyrosine (SLAY) motifs that bind to several integrins and mediate a wide range of cellular processes. In the present study, the proangiogenic effects of a 20-amino-acid OPN peptide (OPNpt20) containing RGD and SLAY motifs were examined in human umbilical vein endothelial cells (HUVECs) and in a rat focal cerebral ischemia model. OPNpt20 exerted robust proangiogenic effects in HUVECs by promoting proliferation, migration and tube formation...
January 19, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29350678/pik3r3-regulates-ppar%C3%AE-expression-to-stimulate-fatty-acid-%C3%AE-oxidation-and-decrease-hepatosteatosis
#3
Xi Yang, Yinjia Fu, Fuqing Hu, Xuelai Luo, Junbo Hu, Guihua Wang
Phosphatidylinositol 3-kinase (PI3K) signaling plays an important role in the regulation of cellular lipid metabolism and non-alcoholic fatty liver disease (NAFLD). However, little is known about the role of the regulatory subunits of PI3K in lipid metabolism and NAFLD. In this study, we characterized the functional role of PIK3R3 in fasting-induced hepatic lipid metabolism. In this study, we showed that the overexpression of PIK3R3 promoted hepatic fatty acid oxidation via PIK3R3-induced expression of PPARα, thus improving the fatty liver phenotype in high-fat diet (HFD)-induced mice...
January 19, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29350677/critical-effects-of-long-non-coding-rna-on-fibrosis-diseases
#4
REVIEW
Yue Zhang, Gang Luo, Yi Zhang, Mengjie Zhang, Jian Zhou, Weiwu Gao, Xiuyun Xuan, Xia Yang, Di Yang, Zhiqiang Tian, Bing Ni, Jun Tang
The expression or dysfunction of long non-coding RNAs (lncRNAs) is closely related to various hereditary diseases, autoimmune diseases, metabolic diseases and tumors. LncRNAs were also recently recognized as functional regulators of fibrosis, which is a secondary process in many of these diseases and a primary pathology in fibrosis diseases. We review the latest findings on lncRNAs in fibrosis diseases of the liver, myocardium, kidney, lung and peritoneum. We also discuss the potential of disease-related lncRNAs as therapeutic targets for the clinical treatment of human fibrosis diseases...
January 19, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29328072/immunomodulatory-effect-of-cd200-positive-human-placenta-derived-stem-cells-in-the-early-phase-of-stroke
#5
TaeHo Kong, Ji-Min Park, Ji Hyon Jang, C-Yoon Kim, Sang-Hun Bae, Yuri Choi, Yun-Hwa Jeong, Chul Kim, Sung Woon Chang, Joopyung Kim, Jisook Moon
Human placenta amniotic membrane-derived mesenchymal stem cells (AMSCs) regulate immune responses, and this property can be exploited to treat stroke patients via cell therapy. We investigated the expression profile of AMSCs cultured under hypoxic conditions and observed interesting expression changes in various genes involved in immune regulation. CD200, an anti-inflammatory factor and positive regulator of TGF-β, was more highly expressed under hypoxic conditions than normoxic conditions. Furthermore, AMSCs exhibited inhibition of pro-inflammatory cytokine expression in co-cultures with LPS-primed BV2 microglia, and this effect was decreased in CD200-silenced AMSCs...
January 12, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29328071/sumoylation-of-histone-deacetylase-1-regulates-myod-signaling-during-myogenesis
#6
Hosouk Joung, Sehee Kwon, Kyoung-Hoon Kim, Yun-Gyeong Lee, Sera Shin, Duk-Hwa Kwon, Yeong-Un Lee, Taewon Kook, Nakwon Choe, Jeong Chul Kim, Young-Kook Kim, Gwang Hyeon Eom, Hyun Kook
Sumoylation, the conjugation of a small ubiquitin-like modifier (SUMO) protein to a target, has diverse cellular effects. However, the functional roles of the SUMO modification during myogenesis have not been fully elucidated. Here, we report that basal sumoylation of histone deacetylase 1 (HDAC1) enhances the deacetylation of MyoD in undifferentiated myoblasts, whereas further sumoylation of HDAC1 contributes to switching its binding partners from MyoD to Rb to induce myocyte differentiation. Differentiation in C2C12 skeletal myoblasts induced new immunoblot bands above HDAC1 that were gradually enhanced during differentiation...
January 12, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29328070/nerve-growth-factor-upregulates-sirtuin-1-expression-in-cholestasis-a-potential-therapeutic-target
#7
Ming-Shian Tsai, Po-Huang Lee, Cheuk-Kwan Sun, Ting-Chia Chiu, Yu-Chun Lin, I-Wei Chang, Po-Han Chen, Ying-Hsien Kao
This study investigated the regulatory role of nerve growth factor (NGF) in sirtuin 1 (SIRT1) expression in cholestatic livers. We evaluated the expression of NGF and its cognate receptors in human livers with hepatolithiasis and the effects of NGF therapy on liver injury and hepatic SIRT1 expression in a bile duct ligation (BDL) mouse model. Histopathological and molecular analyses showed that the hepatocytes of human diseased livers expressed NGF, proNGF (a precursor of NGF), TrkA and p75NTR, whereas only p75NTR was upregulated in hepatolithiasis, compared with non-hepatolithiasis livers...
January 12, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29328069/inhibition-of-muc1-biosynthesis-via-threonyl-trna-synthetase-suppresses-pancreatic-cancer-cell-migration
#8
Seung Jae Jeong, Jong Hyun Kim, Beom Jin Lim, Ina Yoon, Ji-Ae Song, Hee-Sun Moon, Doyeun Kim, Dong Ki Lee, Sunghoon Kim
Mucin1 (MUC1), a heterodimeric oncoprotein, containing tandem repeat structures with a high proportion of threonine, is aberrantly overexpressed in many human cancers including pancreatic cancer. Since the overall survival rate of pancreatic cancer patients has remained low for several decades, novel therapeutic approaches are highly needed. Intestinal mucin has been known to be affected by dietary threonine supply since de novo synthesis of mucin proteins is sensitive to luminal threonine concentration. However, it is unknown whether biosynthesis of MUC1 is regulated by threonine in human cancers...
January 12, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29303514/depletion-of-s100a4-stromal-cells-does-not-prevent-hcc-development-but-reduces-the-stem-cell-like-phenotype-of-the-tumors
#9
Jingjing Jiao, Álvaro González, Heather L Stevenson, Mihai Gagea, Hikaru Sugimoto, Raghu Kalluri, Laura Beretta
There is a pressing need for the development of novel approaches to treat and prevent hepatocellular carcinoma (HCC). The S100 calcium-binding protein S100A4 is associated with poor prognosis and metastasis in several human cancers. In addition, a role for S100A4 in modulating cancer-initiating cells stemness properties was recently proposed in head and neck and gastric cancers. Whether S100A4+ stromal cells contribute to tumor onset remains, however, an unanswered question. To address that question, we generated a new mouse model allowing for the depletion of S100A4+ cells in a mouse model of HCC with stemness properties, by crossing mice with hepatic deletion of phosphatase and tensin homolog (PTEN) with mice expressing viral thymidine kinase under the control of S100A4 promoter...
January 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29303513/in-vitro-modeling-of-hepatocellular-carcinoma-molecular-subtypes-for-anti-cancer-drug-assessment
#10
Hadassa Hirschfield, C Billie Bian, Takaaki Higashi, Shigeki Nakagawa, Tizita Z Zeleke, Venugopalan D Nair, Bryan C Fuchs, Yujin Hoshida
Tractable experimental model that accounts for inter-tumor molecular heterogeneity is a key element of anti-cancer drug development. Hepatocellular carcinoma is known to exhibit highly heterogeneous molecular aberrations across the tumors, including somatic genetic and epigenetic alterations. Previous studies showed that molecular tumor subtypes determined by transcriptome, as a comprehensive functional readout, are reproducibly observed across global patient populations irrespective of geographic and etiological variations...
January 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29303512/the-significance-of-intertumor-and-intratumor-heterogeneity-in-liver-cancer
#11
REVIEW
Jinping Liu, Hien Dang, Xin Wei Wang
Genomic analyses of primary liver cancer samples reveal a complex mutational landscape with vast intertumor and intratumor heterogeneity. Different primary liver tumors and subclones within each tumor display striking molecular and biological variations. Consequently, tumor molecular heterogeneity contributes to drug resistance and tumor relapse following therapy, which poses a substantial obstruction to improving outcomes of patients with liver cancer. There is an urgent need to the compositional and functional understanding of tumor heterogeneity...
January 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29303511/a-gene-expression-signature-of-foxm1-predicts-the-prognosis-of-hepatocellular-carcinoma
#12
Bic-Na Song, In-Sun Chu
FOXM1 (Forkhead box M1) is a key regulator of tumorigenesis. Previous studies demonstrated that FOXM1 overexpression was strongly correlated with poor prognosis in various cancers, including hepatocellular carcinoma (HCC). In this study, we examined an association between the gene expression signature of FOXM1 and HCC patient outcome. The co-expressed gene set of FOXM1, which is significantly associated with the prognosis of HCC patients, was identified by analyzing the gene expression profiles of 100 patients with HCC, and this gene set was validated in two independent HCC patient cohorts (n=573)...
January 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29303510/loss-of-pten-synergizes-with-c-met-to-promote-hepatocellular-carcinoma-development-via-mtorc2-pathway
#13
Zhong Xu, Junjie Hu, Hui Cao, Maria G Pilo, Antonio Cigliano, Zixuan Shao, Meng Xu, Silvia Ribback, Frank Dombrowski, Diego F Calvisi, Xin Chen
Hepatocellular carcinoma (HCC) is a deadly malignancy with limited treatment options. Activation of the AKT/mTOR cascade is one of the most frequent events along hepatocarcinogenesis. mTOR is a serine/threonine kinase and presents in two distinct complexes: mTORC1 and mTORC2. While mTORC1 has been extensively studied in HCC, the functional contribution of mTORC2 during hepatocarcinogenesis has not been well characterized, especially in vivo. Pten expression is one of the major mechanisms leading to the aberrant activation of the AKT/mTOR signaling...
January 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29303509/hippo-pathway-coactivators-yap-and-taz-are-required-to-coordinate-mammalian-liver-regeneration
#14
Li Lu, Milton J Finegold, Randy L Johnson
The mammalian liver has a remarkable capacity for repair following injury. Removal of up to two-third of liver mass results in a series of events that include extracellular matrix remodeling, coordinated hepatic cell cycle re-entry, restoration of liver mass and tissue remodeling to return the damaged liver to its normal state. Although there has been considerable advancement of our knowledge concerning the regenerative capacity of the mammalian liver, many outstanding questions remaining, such as: how does the regenerating liver stop proliferating when appropriate mass is restored and how do these mechanisms relate to normal regulation of organ size during development? Hippo pathway has been proposed to be central in mediating both events: organ size control during development and following regeneration...
January 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29303508/glutamine-synthetase-mediates-sorafenib-sensitivity-in-%C3%AE-catenin-active-hepatocellular-carcinoma-cells
#15
Bo Hwa Sohn, In Young Park, Ji-Hyun Shin, Sun Young Yim, Ju-Seog Lee
The gene encoding β-catenin is frequently mutated in hepatocellular carcinoma cells. While the oncogenicity of β-catenin has been extensively studied, β-catenin's role in hepatocellular carcinoma tumor metabolism is currently less well understood. In this study, we found that β-catenin regulates the expression of glutamine synthetase and triggers a series of metabolic changes leading to induction of autophagy in hepatocellular carcinoma cells. β-Catenin-active Hep3B and HepG2 cells exhibited higher basal levels of autophagic activity than did β-catenin wild-type cells...
January 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29303507/t-cell-immune-regulator-1-enhances-metastasis-in-hepatocellular-carcinoma
#16
Hee Doo Yang, Jung Woo Eun, Kyung-Bun Lee, Qingyu Shen, Hyung Seok Kim, Sang Yean Kim, Dong-Wan Seo, Won Sang Park, Jung Young Lee, Suk Woo Nam
Recurrence and metastasis are major challenges in the management of hepatocellular carcinoma (HCC) patients after resection. To identify a metastasis-associated gene signature, we performed comparative gene expression analysis with recurrent HCC tissues from HCC patients who underwent partial or total hepatectomy and from non-metastatic primary HCC tissues. From this, we were able to identify genes associated with HCC recurrence. TCIRG1 (T-Cell Immune Regulator 1) was one of the aberrantly overexpressed genes in patients with recurrent HCC who had undergone total hepatectomy...
January 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29303506/deciphering-cellular-and-molecular-causes-of-the-tumor-functional-heterogeneity-of-liver-cancer
#17
EDITORIAL
Suk Woo Nam
No abstract text is available yet for this article.
January 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29244790/lentivirus-mediated-silencing-of-the-ptc1-and-ptc2-genes-promotes-recovery-from-spinal-cord-injury-by-activating-the-hedgehog-signaling-pathway-in-a-rat-model
#18
Ya-Dong Zhang, Zhong-Sheng Zhu, Dong Zhang, Zhen Zhang, Bin Ma, Shi-Chang Zhao, Feng Xue
This study aimed to investigate the effect of Patched-1 (PTC1) and PTC2 silencing in a rat model, on Hedgehog (Hh) pathway-mediated recovery from spinal cord injury (SCI). An analytical emphasis on the relationship between the sonic hedgehog (Shh) pathway and nerve regeneration was explored. A total of 126 rats were divided into normal, sham, SCI, negative control (NC), PTC1-RNAi, PTC2-RNAi and PTC1/PTC2-RNAi groups. The Basso, Beattie and Bresnahan (BBB) scale was employed to assess hind limb motor function...
December 15, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29244789/pigment-epithelium-derived-factor-from-arpe19-promotes-proliferation-and-inhibits-apoptosis-of-human-umbilical-mesenchymal-stem-cells-in-serum-free-medium
#19
Dah-Ching Ding, Yao-Tseng Wen, Rong-Kung Tsai
Clinical expansion of mesenchymal stem cells (MSCs) is hampered by the lack of knowledge regarding how to prevent MSC apoptosis and promote their proliferation in serum-free medium. Our in vitro studies demonstrated that human umbilical cord MSCs (HUCMSCs) underwent apoptosis in the serum-free medium. When HUCMSCs were co-cultured with retinal pigment epithelial cells (ARPE19), however, HUCMSCs exhibited normal growth and morphology in serum-free medium. Their colony formation was promoted by the conditioned medium (CM) of ARPE19 cells on Matrigel...
December 15, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29244788/dual-modulation-of-human-hepatic-zonation-via-canonical-and-non-canonical-wnt-pathways
#20
Laura McEnerney, Kara Duncan, Bo-Ram Bang, Sandra Elmasry, Meng Li, Toshio Miki, Sadeesh K Ramakrishnan, Yatrik M Shah, Takeshi Saito
The hepatic lobule is divided into three zones along the portal-central vein axis. Hepatocytes within each zone exhibit a distinctive gene expression profile that coordinates their metabolic compartmentalization. The zone-dependent heterogeneity of hepatocytes has been hypothesized to result from the differential degree of exposure to oxygen, nutrition and gut-derived toxins. In addition, the gradient of Wnt signaling that increases towards the central vein seen in rodent models is believed to play a critical role in shaping zonation...
December 15, 2017: Experimental & Molecular Medicine
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