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Hao Mei, Lianna Li, Michael Griswold, Thomas Mosley
Seven gene sets were significantly enriched for SNP associations with diabetes, and considered as potential diabetes pathways in a previous meta-analysis of diabetes GWAS. This study aims to examine if these gene sets also have expression associations with diabetes. The analysis was conducted using pooled data from 23 diabetes gene expression studies. Gene associations were examined using linear modeling with an empirical Bayes approach, and pathway associations were investigated by testing enrichment for significant genes...
2018: Frontiers in Genetics
Yubin Shin, Do Yeon Kim, Je Yeong Ko, Yu Mi Woo, Jong Hoon Park
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited disorders. ADPKD is caused by mutations in the gene encoding either polycystic kidney disease 1 ( PKD1) or polycystic kidney disease 2 ( PKD2). Patients with ADPKD show progressive growth of cystic fluid-filled renal cysts. Here, we used Pkd2f/f control mice and Pkd2f/f :HoxB7-Cre experimental mice, which are bred to have a conditional deletion of Pkd2 in the collecting ducts, and analyzed the expression pattern of microRNAs (miRNAs) of kidney tissues from Pkd2f/f and Pkd2f/f :HoxB7-Cre mice...
February 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Nele Cosemans, Laura Vandenhove, Jarymke Maljaars, Hilde Van Esch, Koenraad Devriendt, Amanda Baldwin, Jean-Pierre Fryns, Ilse Noens, Hilde Peeters
We describe a patient with a de novo balanced translocation 46,XY,t(9; 13)(q31.2; q22.1) and autism spectrum disorder, intellectual disability, a metopic craniosynostosis, a corpus callosum dysgenesis and dysmorphic facial features, most notably ptosis. Breakpoint mapping was performed by means of targeted locus amplification (TLA) and sequencing, because conventional breakpoint mapping by means of fluorescent in situ hybridization and long-range PCR was hampered by a complex submicroscopic rearrangement. The translocation breakpoints directly affected the genes KLF12 (chromosome 13) and ZNF462 (chromosome 9)...
February 7, 2018: European Journal of Medical Genetics
Chenyang Huang, Yue Jiang, Jianjun Zhou, Qiang Yan, Ruiwei Jiang, Xi Cheng, Jun Xing, Lijun Ding, Jianxin Sun, Guijun Yan, Haixiang Sun
BACKGROUND: Decidualization is a prerequisite for successful implantation and the establishment of pregnancy. A critical role of impaired decidualization in subfertility has been established. In human endometrial stromal cells (hESCs), Krüppel-like factor 12 (KLF12) and Nur77 are novel regulators of decidualization. We investigated whether KLF12 impaired the decidualization of hESCs in recurrent implantation failure (RIF) patients. METHODS: Endometrial tissues and hESCs were collected from RIF patients (n = 34) and fertile controls (n = 30) for in vitro analysis...
March 31, 2017: Reproductive Biology and Endocrinology: RB&E
Kai-Yu Sun, Tao Peng, Zhe Chen, Peng Song, Xu-Hong Zhou
Emerging studies have shown that long noncoding RNAs (lncRNAs) play critical roles in carcinogenesis and progression, including human nasopharyngeal carcinoma (NPC). The correlation between lncRNAs expression and NPC development has not been well identified in the recent literature. Recently, high-through put analysis reveals that LOC100129148 is highly expressed in NPC. However, whether the aberrant expression of LOC100129148 in NPC is corrected with tumorigenesis or prognosis has not been investigated. Herein, we identified that LOC100129148 was up-regulated in NPC tissues and cell lines, and higher expression of LOC100129148 resulted in a markedly poorer survival time...
March 21, 2017: Aging
Amy E Adkins, Laura M Hack, Tim B Bigdeli, Vernell S Williamson, G Omari McMichael, Mohammed Mamdani, Alexis C Edwards, Fazil Aliev, Robin F Chan, Poonam Bhandari, Richard C Raabe, Joseph T Alaimo, GinaMari G Blackwell, Arden Moscati, Ryan S Poland, Benjamin Rood, Diana G Patterson, Dermot Walsh, John B Whitfield, Gu Zhu, Grant W Montgomery, Anjali K Henders, Nicholas G Martin, Andrew C Heath, Pamela A F Madden, Josef Frank, Monika Ridinger, Norbert Wodarz, Michael Soyka, Peter Zill, Marcus Ising, Markus M Nöthen, Falk Kiefer, Marcella Rietschel, Joel Gelernter, Richard Sherva, Ryan Koesterer, Laura Almasy, Hongyu Zhao, Henry R Kranzler, Lindsay A Farrer, Brion S Maher, Carol A Prescott, Danielle M Dick, Silviu A Bacanu, Laura D Mathies, Andrew G Davies, Vladimir I Vladimirov, Mike Grotewiel, M Scott Bowers, Jill C Bettinger, Bradley T Webb, Michael F Miles, Kenneth S Kendler, Brien P Riley
BACKGROUND: Alcohol dependence (AD) shows evidence for genetic liability, but genes influencing risk remain largely unidentified. METHODS: We conducted a genomewide association study in 706 related AD cases and 1,748 unscreened population controls from Ireland. We sought replication in 15,496 samples of European descent. We used model organisms (MOs) to assess the role of orthologous genes in ethanol (EtOH)-response behaviors. We tested 1 primate-specific gene for expression differences in case/control postmortem brain tissue...
May 2017: Alcoholism, Clinical and Experimental Research
Celia S L Mak, Mingo M H Yung, Lynn M N Hui, Leanne L Leung, Rui Liang, Kangmei Chen, Stephanie S Liu, Yiming Qin, Thomas H Y Leung, Kai-Fai Lee, Karen K L Chan, Hextan Y S Ngan, David W Chan
BACKGROUND: Cancer metastasis is determined by the formation of the metastatic niche and the ability of cancer cells to adapt to microenvironmental stresses. Anoikis resistance is a fundamental feature of metastatic cancer cell survival during metastatic cancer progression. However, the mechanisms underlying anoikis resistance in ovarian cancer are still unclear. METHODS: Expressions of miRNA-141 and its downstream targets were evaluated by qPCR, Western blotting, Immunohistochemical (IHC) and in situ hybridization (ISH) assays...
January 17, 2017: Molecular Cancer
Raja Rajeswary Thanmalagan, Leimarembi Devi Naorem, Amouda Venkatesan
Breast cancer affects every 1 of 3000 pregnant women or in the first post-partum year is referred as Pregnancy Associated Breast Cancer (PABC) in mid 30s. Even-though rare disease, classified under hormone receptor negative status which metastasis quickly to other parts by extra cellular matrix degradation. Hence it is important to find an optimal treatment option for a PABC patient. Also additional care should be taken to choose the drug; in order to avoid fetal malformation and post-partum stage side-effects...
July 2017: Pathology Oncology Research: POR
Jason W Hoskins, Abdisamad Ibrahim, Mickey A Emmanuel, Sarah M Manmiller, Yinglun Wu, Maura O'Neill, Jinping Jia, Irene Collins, Mingfeng Zhang, Janelle V Thomas, Lauren M Rost, Sudipto Das, Hemang Parikh, Jefferson M Haake, Gail L Matters, Robert C Kurtz, William R Bamlet, Alison Klein, Rachael Stolzenberg-Solomon, Brian M Wolpin, Ronit Yarden, Zhaoming Wang, Jill Smith, Sara H Olson, Thorkell Andresson, Gloria M Petersen, Laufey T Amundadottir
Genome-wide association studies (GWAS) have identified multiple common susceptibility loci for pancreatic cancer. Here we report fine-mapping and functional analysis of one such locus residing in a 610 kb gene desert on chr13q22.1 (marked by rs9543325). The closest candidate genes, KLF5, KLF12, PIBF1, DIS3 and BORA, range in distance from 265-586 kb. Sequencing three sub-regions containing the top ranked SNPs by imputation P-value revealed a 30 bp insertion/deletion (indel) variant that was significantly associated with pancreatic cancer risk (rs386772267, P = 2...
August 30, 2016: Human Molecular Genetics
Shuai-Shuai Zhang, Yan Xu, Shu-Hui Deng, Chang-Hong Li, Wen Zhou, Lu-Gui Qiu
UNLABELLED: Objectiive:To explore the effect of miR137 target gene MITF on the prognosis of multiple myeloma (MM). METHODS: The target genes of miR137 were predicted by software, the GFP analysis was carried out for detecting MITF as the prognosis of multiple myeloma. The cell line overexpressing miR137 in MM cell line was constructed. Real-time qPCR and Western blot were used to detect the expression of MITF in this cell line. RESULTS: The target genes of miR137 were MITF, BUE2H, SH3BP5 and KLF12...
August 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
Yantao Du, Yichen Chen, Furong Wang, Liankun Gu
Aberrant expression of miR-137 has been reported in many kinds of cancers, but its mechanisms seem to be diversely. In the present study, we compared the expression level of miR-137 in 18 paired gastric cancer (GC) samples and surgical margin (SM) samples by RNA extraction and quantitative real-time PCR (QRT-PCR). Then, we investigated the effects of miR-137 on cell proliferation, cell cycle, and cell migration separately by cell growth counting assay, cell cycle analysis, and transwell assay. Candidate targets of miR-137 were selected by biological information analysis from the intersection of miRDB, Pictar, and TarScan...
October 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
B Guan, Q Li, X H Li, X J Zhou
OBJECTIVE: To identify basal-like breast carcinoma (BLBC)-specific microRNA (miRs) and its target gene and to investigate the distinct biological function. METHOD: Krüppel-like factor 12 (KLF12) 3'-UTR was constructed and luciferase reporter assay was performed for target gene. Expression levels of miR including its target genes were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry (IHC). Further functional analyses were conducted which included apoptosis...
July 12, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Sun-Hee Kim, Yun-Yong Park, Sung-Nam Cho, Ofer Margalit, Dingzhi Wang, Raymond N DuBois
Krüppel-like factor 12 (KLF12) is a transcription factor that plays a role in normal kidney development and repression of decidualization. KLF12 is frequently elevated in esophageal adenocarcinoma and has been reported to promote gastric cancer progression. Here, we examined the role of KLF12 in colorectal cancer (CRC). Indeed, KLF12 promotes tumor growth by directly activating early growth response protein 1 (EGR1). The levels of KLF12 and EGR1 correlate synergistically with a poor prognosis. These results indicate that KLF12 likely plays an important role in CRC and could serve as a potential prognostic marker and therapeutic target...
2016: PloS One
H-Q Zhou, Q-C Chen, Z-T Qiu, W-L Tan, C-Q Mo, S-W Gao
OBJECTIVE: Pancreatic neuroendocrine tumors are relatively rare pancreatic neoplasms over the world. Investigations of the molecular biology of PNETs are insufficient for nowadays. We aimed to explore the expression of microRNA and messenger RNA and regulatory processes underlying pancreatic neuroendocrine tumors. MATERIALS AND METHODS: The messenger RNA and microRNA expression profile of GSE43796 were downloaded, including 6 samples with pancreatic neuroendocrine tumors and 5 healthy samples...
July 2016: European Review for Medical and Pharmacological Sciences
Bing Guan, Qing Li, Li Shen, Qiu Rao, Yan Wang, Yun Zhu, Xiao-Jun Zhou, Xiao-Hong Li
We investigated microRNAs (miRs) specific to its target gene and exerting distinct biological functions for basal-like breast carcinoma (BLBC). Total RNA was extracted and subjected to miR microarray and bioinformatics analysis. Based on the comprehensive analysis, expression of miRs including its target was analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blot analysis and immunohistochemistry (IHC). Further functional analyses were conducted including proliferation, invasion and apoptosis...
August 2016: International Journal of Oncology
Yong-Biao Zhang, Jintian Hu, Jiao Zhang, Xu Zhou, Xin Li, Chaohao Gu, Tun Liu, Yangchun Xie, Jiqiang Liu, Mingliang Gu, Panpan Wang, Tingting Wu, Jin Qian, Yue Wang, Xiaoqun Dong, Jun Yu, Qingguo Zhang
Craniofacial microsomia (CFM) is a rare congenital anomaly that involves immature derivatives from the first and second pharyngeal arches. The genetic pathogenesis of CFM is still unclear. Here we interrogate 0.9 million genetic variants in 939 CFM cases and 2,012 controls from China. After genotyping of an additional 443 cases and 1,669 controls, we identify 8 significantly associated loci with the most significant SNP rs13089920 (logistic regression P=2.15 × 10(-120)) and 5 suggestive loci. The above 13 associated loci, harboured by candidates of ROBO1, GATA3, GBX2, FGF3, NRP2, EDNRB, SHROOM3, SEMA7A, PLCD3, KLF12 and EPAS1, are found to be enriched for genes involved in neural crest cell (NCC) development and vasculogenesis...
February 8, 2016: Nature Communications
N Godin-Heymann, S Brabetz, M M Murillo, M Saponaro, C R Santos, A Lobley, P East, P Chakravarty, N Matthews, G Kelly, S Jordan, E Castellano, J Downward
Suppression of detachment-induced cell death, known as anoikis, is an essential step for cancer metastasis to occur. We report here that expression of KLF12, a member of the Kruppel-like family of transcription factors, is downregulated in lung cancer cell lines that have been selected to grow in the absence of cell adhesion. Knockdown of KLF12 in parental cells results in decreased apoptosis following cell detachment from matrix. KLF12 regulates anoikis by promoting the cell cycle transition through S phase and therefore cell proliferation...
June 23, 2016: Oncogene
Hui Zhang, Xudong Zhu, Jing Chen, Yue Jiang, Qun Zhang, Chengcai Kong, Jun Xing, Lijun Ding, Zhenyu Diao, Xin Zhen, Haixiang Sun, Guijun Yan
BACKGROUND: Decidualization is a prerequisite for successful implantation and the establishment of pregnancy. Krüppel-like factor 12 (KLF12) is a negative regulator of endometrial decidualization in vitro. We investigated whether KLF12 was associated with impaired decidualization under conditions of repeated implantation failure (RIF). METHODS: Uterine tissues were collected from a mouse model of early pregnancy and artificial decidualization for immunohistochemistry, Western blot and real-time PCR analysis...
July 30, 2015: Reproductive Biology and Endocrinology: RB&E
Sabine Hünten, Markus Kaller, Friedel Drepper, Silke Oeljeklaus, Thomas Bonfert, Florian Erhard, Anne Dueck, Norbert Eichner, Caroline C Friedel, Gunter Meister, Ralf Zimmer, Bettina Warscheid, Heiko Hermeking
We determined the effect of p53 activation on de novo protein synthesis using quantitative proteomics (pulsed stable isotope labeling with amino acids in cell culture/pSILAC) in the colorectal cancer cell line SW480. This was combined with mRNA and noncoding RNA expression analyses by next generation sequencing (RNA-, miR-Seq). Furthermore, genome-wide DNA binding of p53 was analyzed by chromatin-immunoprecipitation (ChIP-Seq). Thereby, we identified differentially regulated proteins (542 up, 569 down), mRNAs (1258 up, 415 down), miRNAs (111 up, 95 down) and lncRNAs (270 up, 123 down)...
October 2015: Molecular & Cellular Proteomics: MCP
Qun Zhang, Hui Zhang, Yue Jiang, Bai Xue, Zhenyu Diao, Lijun Ding, Xin Zhen, Haixiang Sun, Guijun Yan, Yali Hu
BACKGROUND: The transformation of endometrium into decidua is essential for normal implantation of the blastocyst. However, the post-transcriptional regulation and the miRNAs involved in decidualization remain poorly understood. Here, we examined microRNA-181a (miR-181a) expression in decidualized human endometrial stromal cell (hESC). In addition, we investigated the functional effect of miR-181a on hESC decidualization in vitro. METHODS: Quantitative real-time PCR (qRT-PCR) was used to detect the profile of miR-181a in decidualized hESC...
March 26, 2015: Reproductive Biology and Endocrinology: RB&E
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