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A K Schneider, Giuseppe Cama, Mandeep Ghuman, Francis J Hughes, Borzo Gharibi
Sprouty 2 (Spry2), an inhibitor of MAP kinase signalling was previously shown by our group to be induced during mechanical loading of mesenchymal stem cells (MSCs). Here we studied the implication of Spry2 activation during mechanical loading and chemically induced MSC differentiation. Spry 2 expression showed an immediate early response during mechanical loading and chemical induction of osteogenic differentiation and followed the same pattern as osteogenic associated gene FosB and was necessary for the induction of FosB, as Spry 2 knockdown also abrogated the upregulation of FosB expression...
April 7, 2017: Journal of Cellular Biochemistry
Patricia G Tremblay, Marc-André Sirard
The developmental competence of an oocyte is its capacity to resume maturation, undergo successful fertilization and reach the blastocyst stage. This competence is acquired through interaction with somatic cells of the follicle. Cumulus and granulosa cells support oocyte development while the oocyte influences follicular cell growth and differentiation. Studies suggest that follicle-stimulating hormone and luteinizing hormone play an essential role in oocyte competence acquisition through signalling initiated by protein kinases A and C (PKA and PKC) in granulosa cells...
April 5, 2017: Biology of Reproduction
Zachary Pappalardo, Deeksha G Chopra, Thomas G Hennings, Hunter Richards, Justin Choe, Katherine Yang, Luc Baeyens, Kenny Ang, Steven Chen, Michelle Arkin, Michael S German, Michael T McManus, Gregory M Ku
Insulin production by the pancreatic beta cell is required for normal glucose homeostasis. While key transcription factors that bind to the insulin promoter are known, relatively little is known about the upstream regulators of insulin transcription. Using a whole genome RNA interference screen, we uncovered 26 novel regulators of insulin transcription that regulate diverse processes including oxidative phosphorylation, vesicle traffic, and the unfolded protein response(UPR). We focused on Spry2 -- a gene implicated in human type 2 diabetes by genome wide association studies but without a clear connection to glucose homeostasis...
February 28, 2017: Diabetes
Xianlong Gao, Kristin C Hicks, Paul Neumann, Tarun B Patel
Receptor Tyrosine Kinase (RTK) signaling plays a major role in tumorigenesis and normal development. Sprouty2 (Spry2) attenuates RTK signaling and inhibits processes such as angiogenesis, cell proliferation, migration and survival, which are all upregulated in tumors. Indeed in cancers of the liver, lung, prostate and breast, Spry2 protein levels are markedly decreased correlating with poor patient prognosis and shorter survival. Thus, it is important to understand how expression of Spry2 is regulated. While prior studies have focused on the post-translation regulation of Spry2, very few studies have focused on the transcriptional regulation of SPRY2 gene...
2017: PloS One
Wenying Huo, Guannan Zhao, Jinggang Yin, Xuan Ouyang, Yinan Wang, Chuanhe Yang, Baojing Wang, Peixin Dong, Zhixiang Wang, Hidemichi Watari, Edward Chaum, Lawrence M Pfeffer, Junming Yue
CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats) mediated genome editing is a powerful approach for loss of function studies. Here we report that lentiviral CRISPR/Cas9 vectors are highly efficient in introducing mutations in the precursor miRNA sequence, thus leading to the loss of miRNA expression and function. We constructed four different lentiviral CRISPR/Cas9 vectors that target different regions of the precursor miR-21 sequence and found that these lentiviral CRISPR/Cas9 miR-21 gRNA vectors induced mutations in the precursor sequences as shown by DNA surveyor mutation assay and Sanger sequencing...
2017: Journal of Cancer
Yan-Ting Zhao, Yun-Bo Guo, Lei Gu, Xue-Xin Fan, Hua-Qian Yang, Zheng Chen, Peng Zhou, Qi Yuan, Guang-Ju Ji, Shi-Qiang Wang
Aims: The heart contraction is controlled by the Ca2+-induced Ca2+ release (CICR) between L-type Ca2+ channels and ryanodine receptors (RyRs). The FK506-binding protein FKBP12.6 binds to RyR subunits, but its role in stabilizing RyR function has been debated for long. Recent reports of high-resolution RyR structure show that the HD2 domain that binds to the SPRY2 domain of neighbouring subunit in FKBP-bound RyR1 is detached and invisible in FKBP-null RyR2. The present study was to test the consequence of FKBP12...
March 1, 2017: Cardiovascular Research
Yunfei Xu, Xiaoqing Yang, Zhen Li, Shuo Li, Sen Guo, Sayed Ismail, Hongda Liu, Zhihong Huang, Zongli Zhang, Yuxin Chen, Qing Sun
Fibroblast growth factor receptor 2 (FGFR2) has been identified as a predictive biomarker for unfavorable prognosis of gastric adenocarcinoma. As a well-defined antagonist in FGFR2-induced RAS/ERK activation, ectopic expression of sprouty (SPRY) family was reported in several kinds of cancers except gastric cancer. To explore the clinical significance of SPRY family and its correlation with FGFR2, we detected the expression of FGFR2 and SPRY family in 104 cases of gastric adenocarcinoma and subsequently analyzed their correlations with clinicopathological factors and overall survival rates by univariate and multivariate analysis...
January 17, 2017: Oncotarget
Meng Jiang, Weiyuan Ma, Yumei Gao, Kun Jia, Yan Zhang, Haidong Liu, Qing Sun
Psoriasis is a common inflammatory skin disease but the exact pathogenesis is largely unknown. Interleukin-22 (IL-22) has demonstrated its vital role in T cell-mediated immune response by interacting with keratinocytes in the pathogenesis of psoriasis. Here, we showed the differentially expressed miRNAs and their potential targets in HaCaT cells stimulated by IL-22 using miRNA and mRNA microarrays. We revealed a total of 20 significantly changed (more than 2-fold) miRNAs in HaCaT cells and validated the results with quantitative reverse transcriptase PCR (qRT-PCR)...
December 11, 2016: Experimental Dermatology
Jung-Chien Cheng, Hsun-Ming Chang, Siyuan Xiong, Wai-Kin So, Peter C K Leung
Similar to Drosophila Sprouty (SPRY), mammalian SPRY proteins inhibit the receptor tyrosine kinase-mediated activation of cellular signaling pathways. SPRY2 expression levels have been shown to be down-regulated in human ovarian cancer, and patients with low SPRY2 expression have significantly poorer survival than those with high SPRY2 expression. In addition, epidermal growth factor receptor (EGFR) is overexpressed in human ovarian cancer and is associated with more aggressive clinical behavior and a poor prognosis...
December 6, 2016: Oncotarget
M Clarke, G Volpe, L Sheriff, D Walton, C Ward, W Wei, S Dumon, P García, J Frampton
Myeloproliferative neoplasms (MPN), which overproduce blood cells in the bone marrow, have recently been linked with a genetically determined decrease in expression of the MYB transcription factor. Here, we use a mouse MYB knockdown model with an MPN-like phenotype to show how lower levels of MYB lead to stem cell characteristics in myeloid progenitors. The altered progenitor properties feature elevated cytokine responsiveness, especially to interleukin-3, which results from increased receptor expression and increased MAPK activity leading to enhanced phosphorylation of a key regulator of protein synthesis, ribosomal protein S6...
April 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Jyotsna Nambiar, Chinchu Bose, Meera Venugopal, Asoke Banerji, Tarun B Patel, Geetha B Kumar, Bipin G Nair
Earlier studies from our laboratory have identified Anacardic acid (AA) as a potent inhibitor of gelatinases (MMP-2 and 9), which are over-expressed in a wide variety of cancers (Omanakuttan et al., 2012). Disruption of the finely tuned matrix metalloproteinase (MMP) activator/inhibitor balance plays a decisive role in determining the fate of the cell. The present study demonstrates for the first time, that in addition to regulating the expression as well as activity of gelatinases, AA also inhibits the expression of its endogenous activators like MMP-14 and Extracellular Matrix MetalloProteinase Inducer (EMMPRIN) and induces the expression of its endogenous inhibitor, REversion-inducing Cysteine-rich protein with Kazal motifs (RECK)...
October 11, 2016: Experimental Cell Research
Luis G Rabaneda, Noelia Geribaldi-Doldán, Maribel Murillo-Carretero, Manuel Carrasco, José M Martínez-Salas, Cristina Verástegui, Carmen Castro
Hyperhomocysteinemia reduces neurogenesis in the adult mouse brain. Homocysteine (Hcy) inhibits postnatal neural progenitor cell (NPC) proliferation by specifically impairing the fibroblast growth factor receptor (FGFR)-Erk1/2-cyclin E signaling pathway. We demonstrate herein that the inhibition of FGFR-dependent NPC proliferation induced by Hcy is mediated by its capacity to alter the cellular methylation potential. Our results show that this alteration modified the expression pattern and activity of Sprouty2 (Spry2), a negative regulator of the above mentioned pathway...
December 2016: Biochimica et Biophysica Acta
Jie Yang, Zegao Zhang, Wen Guo, Yuhua Ma, Raila Muhammed Emin, Karima Abudubari, Glmira Hayrat, Hasiyet Wali, Xiaoli Qi, Chunhua Liu, Miaomiao Ma, Pulat Nurbek
The goal of this study was to explore the correlation between single nucleotide polymorphisms (SNPs) and susceptibility to cervical cancer (CC) in a population from Xinjiang Uygur. Participating were 247 patients with CC and 285 healthy women. Fourteen SNPs in nine miRNA genes were selected. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression analysis. Multivariate logistic regression analysis was used to assess the correlation of SNPs with CC. The minor allele "C" of rs300574 in SPRY1 was associated with an increased risk of CC based on analysis of the allele, codominant, recessive and log-additive models, but an opposite result was found with the over-dominant model...
November 1, 2016: Oncotarget
Jung-Chien Cheng, Lanlan Fang, Hsun-Ming Chang, Ying-Pu Sun, Peter C K Leung
Sprouty2 (SPRY2) is an important intracellular regulator for epidermal growth factor receptor (EGFR)-mediated ERK1/2 signaling. In human granulosa cells, although SPRY2 is expressed, its regulation and function remains complete unknown and must be defined. Our previous study has shown that human chorionic gonadotropin (hCG)/luteinizing hormone (LH) up-regulates the expression levels of EGF-like growth factor, amphiregulin (AREG), which subsequently contributes to the hCG/LH-induced COX-2 expression and PGE2 production...
2016: Scientific Reports
Yonis Soubere Mahamoud, Meziane Aite, Catherine Martin, Maxim Zhadobov, Ronan Sauleau, Yves Le Dréan, Denis Habauzit
Millimeter Waves (MMW) will be used in the next-generation of high-speed wireless technologies, especially in future Ultra-Broadband small cells in 5G cellular networks. Therefore, their biocompatibilities must be evaluated prior to their massive deployment. Using a microarray-based approach, we analyzed modifications to the whole genome of a human keratinocyte model that was exposed at 60.4 GHz-MMW at an incident power density (IPD) of 20 mW/cm2 for 3 hours in athermic conditions. No keratinocyte transcriptome modifications were observed...
2016: PloS One
Xuhua Tan, Yi Zhu, Chuan Chen, Xiaoyun Chen, Yingyan Qin, Bo Qu, Lixia Luo, Haotian Lin, Mingxing Wu, Weirong Chen, Yizhi Liu
Transforming growth factor β (TGFβ)-induced epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) plays a key role in the pathogenesis of anterior subcapsular cataract (ASC) and capsule opacification. In mouse lens, Sprouty2 (Spry2) has a negative regulatory role on TGFβ signaling. However, the regulation of Spry2 during ASC development and how Spry2 modulates TGFβ signaling pathway in human LECs have not been characterized. Here, we demonstrate that Spry2 expression level is decreased in anterior capsule LECs of ASC patients...
2016: PloS One
Kristin C Hicks, Tarun B Patel
The α-subunits of hypoxia-inducible factors (HIF1α and HIF2α) promote transcription of genes that regulate glycolysis and cell survival and growth. Sprouty2 (Spry2) is a modulator of receptor tyrosine kinase signaling and inhibits cell proliferation by a number of different mechanisms. Because of the seemingly opposite actions of HIFα subunits and Spry2 on cellular processes, we investigated whether Spry2 regulates the levels of HIF1α and HIF2α proteins. In cell lines from different types of tumors in which the decreased protein levels of Spry2 have been associated with poor prognosis, silencing of Spry2 elevated HIF1α protein levels...
August 5, 2016: Journal of Biological Chemistry
Kaiming Wu, Changhong Ye, Lin Lin, Yimin Chu, Meng Ji, Weiping Dai, Xin Zeng, Yong Lin
MicroRNA-21 (miR-21) has emerged as a critical regulatory molecule and an important serum marker in hepatic fibrogenesis. The aim of the present study was to investigate the role of inhibiting miR-21 on hepatic fibrosis treatment. Serum miR-21 levels in 60 healthy individuals and 180 patients with different stages of liver cirrhosis were examined, miR-21 levels in normal or cirrhotic human liver tissues (n=10 each) were also detected. An adenoviral vector (Ad-TuD-21) carrying the sponging ToughDecoy (TuD)-RNA sequence against miR-21 was constructed to reduce miR-21 expression efficiently in vitro and in vivo Histological and immunohistological examinations were performed to evaluate the inhibitory effects and mechanism of Ad-TuD-21 delivery into carbon tetrachloride (CCl4) induced hepatic fibrosis rats by targeting extracellular signal-regulated kinase 1 (ERK1) signalling in hepatic stellate cells (HSC) and hepatocyte epithelial-mesenchymal transition (EMT)...
August 1, 2016: Clinical Science (1979-)
Adriane Joo, Roger Long, Zhiqiang Cheng, Courtney Alexander, Wenhan Chang, Ophir D Klein
Skeletal development is regulated by the coordinated activity of signaling molecules that are both produced locally by cartilage and bone cells and also circulate systemically. During embryonic development and postnatal bone remodeling, receptor tyrosine kinase (RTK) superfamily members play critical roles in the proliferation, survival, and differentiation of chondrocytes, osteoblasts, osteoclasts, and other bone cells. Recently, several molecules that regulate RTK signaling have been identified, including the four members of the Sprouty (Spry) family (Spry1-4)...
July 2016: Bone
Nadine Norton, Pooja P Advani, Daniel J Serie, Xochiquetzal J Geiger, Brian M Necela, Bianca C Axenfeld, Jennifer M Kachergus, Ryan W Feathers, Jennifer M Carr, Julia E Crook, Alvaro Moreno-Aspitia, Panos Z Anastasiadis, Edith A Perez, E Aubrey Thompson
BACKGROUND: Invasive lobular carcinoma (ILC) comprises approximately ~10-20% of breast cancers. In general, multifocal/multicentric (MF/MC) breast cancer has been associated with an increased rate of regional lymph node metastases. Tumor heterogeneity between foci represents a largely unstudied source of genomic variation in those rare patients with MF/MC ILC. METHODS: We characterized gene expression and copy number in 2 or more foci from 11 patients with MF/MC ILC (all ER+, HER2-) and adjacent normal tissue...
2016: PloS One
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