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Ras protein

Hisateru Komatsu, Tomohiro Iguchi, Takaaki Masuda, Hidenari Hirata, Masami Ueda, Shinya Kidogami, Yushi Ogawa, Kuniaki Sato, Qingjiang Hu, Sho Nambara, Tomoko Saito, Shotaro Sakimura, Ryutaro Uchi, Shuhei Ito, Hidetoshi Eguchi, Keishi Sugimachi, Hidetoshi Eguchi, Yuichiro Doki, Masaki Mori, Koshi Mimori
BACKGROUND: The RND1 gene encodes a protein that belongs to the Rho GTPase family, which regulates various cellular functions. Depletion of RND1 expression activates the oncogenic Ras signaling pathway. In this study, we aimed to clarify the clinical significance of RND1 expression in predicting prognosis and to investigate its biological role in human hepatocellular carcinoma (HCC). METHODS: The association between RND1 expression and clinical outcomes in patients with HCC was analyzed in three independent cohorts: 120 cases resected in our hospital; 370 cases in The Cancer Genome Atlas (TCGA); and 242 cases in GSE14520...
October 21, 2016: Annals of Surgical Oncology
Wenjin Chen, Shengdong Guo, Shenggang Wang
BACKGROUND The purpose of our study was to determine the functional role of microRNA (miR)-16 in chronic inflammatory pain and to disclose its underlying molecular mechanism. MATERIAL AND METHODS Inflammatory pain was induced by injection of complete Freund's adjuvant (CFA) to Wistar rats. The pWPXL-miR-16, PcDNA3.1- Ras-related protein (RAB23), and/or SB203580 were delivered intrathecally to the rats. Behavioral tests were detected at 0 h, 4 h, 1 d, 4 d, 7 d, and 14 d after CFA injection. After behavioral tests, L4-L6 dorsal spinal cord were obtained and the levels of miR-16, RAB23, and phosphorylation of p38 (p-p38) were evaluated by quantitative real-time PCR (qRT-PCR)...
October 22, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Yuanyuan Ji, Zhidong Wang, Zongfang Li, Na Huang, Haiyan Chen, Baohua Li, Bo Hui
Emerging evidence confirms that insulin-like growth factor -II (IGF-II), oncogenes C-myc and N-ras are an essential regulator for development and growth in hepatocellular carcinoma (HCC). Although our previous study also indicated that IGF-II might upregulate levels of oncogenes C-myc and N-ras in hepatoma carcinoma cells, the molecular mechanism had not been fully elucidated. Herein, we successfully silenced IGF-II expression in SMCC-7721 cells by small RNA interference. Functional analysis showed that knockdown of IGF-II significantly suppressed growth and proliferation of SMMC-7721 cells and decreased C-myc and N-ras mRNA and protein levels...
October 18, 2016: Cytokine
Rui-Li Zhang, Jun-Ping Yang, Li-Xia Peng, Li-Sheng Zheng, Ping Xie, Meng-Yao Wang, Yun Cao, Zhi-Ling Zhang, Fang-Jian Zhou, Chao-Nan Qian, Yong-Xing Bao
Clear cell renal cell carcinoma (ccRCC) is a common pathological subtype of renal cancer. Although the recent application of molecular-targeted agents has modestly improved the prognosis of ccRCC patients, their outcome is still poor. It is therefore important to characterize the molecular and biological mechanisms responsible for the development of ccRCC. Approximately 25% ccRCC patients involves the loss of RNA-binding protein QKI at 6q26, but the role of QKI in ccRCC is unknown. Here, we found that QKI-5 was frequently downregulated in ccRCC patients and its down-regulation was significantly associated with clinical features including T status, M status, and differentiation grade, and poorer patient prognosis...
October 21, 2016: Cell Cycle
Bing-Sheng Sun, Yi-Qun Yao, Bao-Xiang Pei, Zhen-Fa Zhang, Chang-Li Wang
BACKGROUND: This study was conducted to investigate the clinical significance of claudin-1 (CLDN1) expression in patients with lung adenocarcinoma. METHODS: We examined CLDN1 protein expression by immunohistochemistry in a tissue microarray from 258 patients with lung adenocarcinoma. We investigated messenger ribonucleic acid (mRNA) expression in H358 (formerly bronchioloalveolar carcinoma) and lung adenocarcinoma cell lines (A549) by real-time reverse transcriptase-polymerase chain reaction...
September 2016: Thoracic Cancer
Laura Schirosi, Annalisa Mazzotta, Giuseppina Opinto, Rosamaria Pinto, Giusi Graziano, Stefania Tommasi, Livia Fucci, Giovanni Simone, Anita Mangia
There is an increasing need to identify new biomarkers in colorectal cancer (CRC) to further characterize this malignancy. β-catenin plays a central role in the Wnt signaling pathway. It also binds Na+/H+ exchanger regulating factor 1 (NHERF1) and interacts with the RAS-association domain family 1, isoform A (RASSF1A), but the mechanisms of this possible crosstalk are still not fully understood. In this study, we analyzed for the first time the different subcellular expression of β-catenin, NHERF1, and RASSF1A and their relationships with RASSF1A methylation in the progression of CRC...
September 27, 2016: Oncotarget
Rita Valenzuela, Maria A Costa-Besada, Javier Iglesias-Gonzalez, Emma Perez-Costas, Begoña Villar-Cheda, Pablo Garrido-Gil, Miguel Melendez-Ferro, Ramon Soto-Otero, Jose L Lanciego, Daniel Henrion, Rafael Franco, Jose L Labandeira-Garcia
The renin-angiotensin system (RAS) was initially considered as a circulating humoral system controlling blood pressure, being kidney the key control organ. In addition to the 'classical' humoral RAS, a second level in RAS, local or tissular RAS, has been identified in a variety of tissues, in which local RAS play a key role in degenerative and aging-related diseases. The local brain RAS plays a major role in brain function and neurodegeneration. It is normally assumed that the effects are mediated by the cell-surface-specific G-protein-coupled angiotensin type 1 and 2 receptors (AT1 and AT2)...
October 20, 2016: Cell Death & Disease
Min Wu, Jinyan Huang, Jianming Zhang, Cyril Benes, Bo Jiao, Ruibao Ren
RAS oncogenic mutations are common in human cancers, but RAS proteins have been difficult to target. We sought to identify pharmacological agents to block the RAS oncogenic signaling by a distinct mechanism. Since the biological activity of RAS proteins rely upon lipid modifications and RAS regulates lipid metabolisms in cancer cells, we screened a bioactive lipid library using a RAS specific cell viability assay. We report the discovery of a new class of inhibitors for RAS transformation. Compounds in the class represented by endocannabinoid N-arachidonoyl dopamine (NADA) can induce cell oncosis, independent of its ability to engage cannabinoid receptors...
October 19, 2016: Molecular Cancer Therapeutics
Yan Wang, Jung-Mao Hsu, Ya'an Kang, Yongkun Wei, Pei-Chih Lee, Shing-Jyh Chang, Yi-Hsin Hsu, Jennifer L Hsu, Hung-Ling Wang, Wei-Chao Chang, Chia-Wei Li, Hsin-Wei Liao, Shih-Shin Chang, Weiya Xia, How-Wen Ko, Chao-Kai Chou, Jason B Fleming, Huamin Wang, Rosa F Hwang, Yue Chen, Jun Qin, Mien-Chie Hung
The oncogenic transcription factor Gli1 is a critical effector in the Hedgehog (Hh) pathway which is necessary for the development and progression of pancreatic ductal adenocarcinoma (PDAC). While TGF-β and K-Ras are known regulators of Gli1 gene transcription in this setting, it is not understood how Gli1 functional activity is regulated. Here we report the identification of Gli1 as a substrate for the protein arginine N-methyltransferase PRMT1 in PDAC. We found that PRMT1 methylates Gli1 at R597, promoting its transcriptional activity by enhancing the binding of Gli1 to its target gene promoters...
October 6, 2016: Cancer Research
Janghyun Yoo, Tae-Sun Lee, Byungsan Choi, Min Ju Shon, Tae-Young Yoon
Extremely weak protein-protein interactions (PPIs), signified by micromolar or even millimolar dissociation constants, are one of the keys to understanding the rapid responses of cellular systems. Although single-molecule methods are particularly useful in determining kinetics of biological processes, their application is largely limited to rather strong interactions because of the diffraction-limited observation volume. In this study, we report a single-molecule method that allows the characterization of PPIs using a prey concentration four orders of magnitude lower than the dissociation constant...
October 19, 2016: Journal of the American Chemical Society
Xiang-Jun Tang, Kuan-Ming Huang, Hui Gui, Jun-Jie Wang, Jun-Ti Lu, Long-Jun Dai, Li Zhang, Gang Wang
As one of the natural herbal flavonoids, myricetin has attracted much research interest, mainly owing to its remarkable anticancer properties and negligible side effects. It holds great potential to be developed as an ideal anticancer drug through improving its bioavailability. This study was performed to investigate the effects of Pluronic-based micelle encapsulation on myricetin-induced cytotoxicity and the mechanisms underlying its anticancer properties in human glioblastoma cells. Cell viability was assessed using a methylthiazol tetrazolium assay and a real-time cell analyzer...
2016: International Journal of Nanomedicine
Masaki Sunagawa, Shinji Mii, Atsushi Enomoto, Takuya Kato, Yoshiki Murakumo, Yukihiro Shiraki, Naoya Asai, Masato Asai, Masato Nagino, Masahide Takahashi
CD109 is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed in several types of human cancers, particularly squamous cell carcinomas. We previously reported that CD109-deficient mice exhibit epidermal hyperplasia and chronic skin inflammation. Although we found that CD109 regulates differentiation of keratinocytes in vivo, the function of CD109 in tumorigenesis remains unknown. In this study, we investigated the role of CD109 in skin tumorigenesis using a two-stage carcinogenesis model in CD109-deficient mice with chronic skin inflammation...
October 14, 2016: Oncotarget
James Scholey
The classical view of the RAS is a linear signaling pathway beginning with the conversion of angiotensinogen to ANG I by renin, an enzyme secreted by the kidney. ANG I is converted to ANG II by angiotensin converting enzyme (ACE) ANG II binds to the G-protein coupled angiotensin II receptor type 1. The RAS is a circulating system but we now know that the RAS is also locally expressed in a number of tissues, including the kidneys and the heart. ANG II exerts adverse hemodynamic and non-hemodynamic effects on renal cells...
September 2016: Journal of Hypertension
Louise Burrell
The renin-angiotensin system (RAS) plays a major role in the pathogenesis of hypertension, a major risk factor for stroke, coronary events, heart failure and kidney disease. Within the RAS, angiotensin converting enzyme (ACE) converts angiotensin (Ang) I into the vasoconstrictor Ang II, which mediates its effects via the angiotensin type 1 receptor (AT1R). An "alternate" arm of the RAS is now known to exist in which the monocarboxypeptidase ACE2 counterbalances the effects of the classic RAS through degradation of the vasoconstrictor peptide, Ang II, and generation of the vasodilatory peptide, Ang 1-7...
September 2016: Journal of Hypertension
Koki Takane, Yu Hasegawa, Lin Bowen, Takashi Yokoo, Shokei Kim-Mitsuyama
OBJECTIVE: Increasing evidences suggest that patients with Alzheimer's disease (AD) show not only cognitive impairment but also physical disorder including cardiac dysfunction and sarcopenia. In this study, we investigated whether central angiotensin II, inducer of oxidative stress, led to the organ dysfunction in a mouse model of AD. DESIGN AND METHOD: 5XFAD which is an animal model of AD and C57BL/6 (WT) were each assigned to 1) normal saline and 2) angiotensin II (20 mg/kg/h) groups...
September 2016: Journal of Hypertension
Yoshitsugu Iwakura, Ryo Morimoto, Kumi Kikuchi, Yoshikiyo Ono, Yuta Tezuka, Yasuko Tsukada, Masahiro Nezu, Yasuhiro Igarashi, Masataka Kudo, Akira Nishiyama, Sadayoshi Ito, Fumitoshi Satoh
OBJECTIVE: High prevalence of renal damage has been demonstrated in patients with primary aldosteronism (PA). However, the original mechanism and onset still be elucidated. The purpose of this study is to investigate the possible original mechanisms of renal damages in PA. DESIGN AND METHOD: Consecutive 72 patients with aldosterone producing adenoma (APA) and 70 patients with essential hypertension (EH) participated. No patients had renal damages defined as eGFR (based on Cystatin C) < 60 ml/min/1...
September 2016: Journal of Hypertension
Masatsugu Horiuchi
Hypertensive patients have greater chances of such cardiovascular events as stroke, coronary heart disease, heart or renal failure, peripheral artery disease, and dementia. It is also well recognized that diabetes increases the cardiovascular risks in concert with hypertension. Therefore, main goals for an innovation of anti-hypertensive therapy would be to achieve further risk reduction by targeting the functional, metabolic, and structural alterations associated with hypertension. Professors Dzau and Braunwald et al proposed the concept of "the cardiovascular disease continuum" in 1991, and that hypertension may trigger the chain of events, leading to end-stage heart disease; however, this concept was quite new at that time, and there was some discussion whether "the cardiovascular disease continuum" is true or not...
September 2016: Journal of Hypertension
Jia-Ying Zhang, Ying Yin, Li Ni, Quan Long, Li You, Qian Zhang, Shan-Yan Lin, Jing Chen
Low-protein diet plus ketoacids (LPD+KA) has been reported to decrease proteinuria in patients with chronic kidney diseases (CKD). However, the mechanisms have not been clarified. As over-activation of intrarenal renin-angiotensin system (RAS) has been shown to play a key role in the progression of CKD, the current study was performed to investigate the direct effects of LPD+KA on intrarenal RAS, independently of renal haemodynamics. In this study, 3/4 subtotal renal ablated rats were fed 18 % normal-protein diet (Nx-NPD), 6 % low-protein diet (Nx-LPD) or 5 % low-protein diet plus 1 % ketoacids (Nx-LPD+KA) for 12 weeks...
October 18, 2016: British Journal of Nutrition
Keiko Shimojima, Yumiko Ondo, Mayumi Matsufuji, Nozomi Sano, Hisashi Tsuru, Tatsuki Oyoshi, Nayuta Higa, Hiroshi Tokimura, Kazunori Arita, Toshiyuki Yamamoto
A female patient presented with developmental delay, distinctive facial features, and congenital anomalies, including a heart defect and premature lambdoid synostosis. The patient showed a paternally inherited 16p13.11 microduplication and a de novo 19p13.3 microdeletion involving the mitogen-activated protein kinase kinase 2 gene (MAP2K2), in which mutations cause the cardio-facio-cutaneous (CFC) syndrome. Reports of patients with overlapping 19p13.3 microdeletions of this region describe similar clinical manifestations including distinctive facial features: prominent forehead, horizontal/down-slanting palpebral fissures, long midface, pointed chin/angular jaw, sparse eyebrows, and underdeveloped cheekbones...
October 14, 2016: European Journal of Medical Genetics
Rane A Harrison, Jia Lu, Martin Carrasco, John Hunter, Anuj Manandhar, Sudershan Gondi, Kenneth D Westover, John R Engen
Structural dynamics of Ras proteins contribute to their activity in signal transduction cascades. Directly targeting Ras proteins with small molecules may rely on movement of a conserved structural motif, switch II. To understand Ras signaling and advance Ras targeting strategies, experimental methods to measure Ras dynamics are required. Here we demonstrate the utility of hydrogen-deuterium exchange mass spectrometry to measure Ras dynamics by studying representatives from two branches of the Ras superfamily, Ras and Rho...
October 14, 2016: Journal of Molecular Biology
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