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Jianjun Sha, Qing Han, Chenfei Chi, Yinjie Zhu, Jiahua Pan, Baijun Dong, Yiran Huang, Weiliang Xia, Wei Xue
Castration-resistant prostate cancers (CRPC) that occur after the failure of androgen-blocking therapies cause most of the deaths in prostate cancer (PCa) patients. In a previous study we identified that PRKAR2B expression is upregulated in CRPC and possesses potentials to develop CRPC. Here we further investigated the underlying mechanism of PRKAR2B in regulating prostate cancer metastasis. We established an androgen-independent LNCaPcell line (LNCaP-AI), and investigated the function of PRKAR2B on regulating cell invasion in vitro and in vivo...
May 15, 2018: Journal of Cellular Biochemistry
J Miao, X Wang, J Bao, S Jin, T Chang, J Xia, L Yang, B Zhu, L Xu, L Zhang, X Gao, Y Chen, J Li, H Gao
Bone weight, defined as the total weight of the bones in all the forequarter and hindquarter joints, can reflect somebody conformation traits and skeletal diseases. To gain a better understanding of the genetic determinants of bone weight, we used a composite strategy including multimarker and rare-marker association to perform genomewide association studies (GWAS) for that character in Simmental cattle. Our strategy consisted of three models: (i) A traditional linear mixed model (LMM) was applied (Q+K-LMM); (ii) single nucleotide polymorphisms (SNPs) with p-values less than ...
April 26, 2018: Journal of Animal Breeding and Genetics, Zeitschrift Für Tierzüchtung und Züchtungsbiologie
Hyemin Yoon, Hoon Jang, Eun-Young Kim, Sohyeon Moon, Sangho Lee, Minha Cho, Hye Jung Cho, Jung Jae Ko, Eun Mi Chang, Kyung-Ah Lee, Youngsok Choi
BACKGROUND/AIMS: Cyclic adenosine monophosphate (cAMP)-dependent type 2 regulatory subunit beta (Prkar2b) is a regulatory isoform of cAMP-dependent protein kinase (PKA), which is the primary target for cAMP actions. In oocytes, PKA and the pentose phosphate pathway (PPP) have important roles during the germinal vesicle (GV) stage arrest of development. Although the roles of the PKA signal pathway have been studied in the development of oocyte, there has been no report on the function of PRKAR2B, a key regulator of PKA...
2018: Cellular Physiology and Biochemistry
Hong-Qiang Chen, Ji Zhao, Yan Li, Li-Xiong He, Yu-Jing Huang, Wei-Qun Shu, Jia Cao, Wen-Bin Liu, Jin-Yi Liu
Microcystin (MC) is a cyclic heptapeptide compound which could lead to the development of hepatocellular carcinoma. However, the underlying epigenetic regulation mechanism is largely unknown. In this study, microcystin-LR (L: lysine, R: arginine, MC-LR) was used to induce the malignant transformation of human hepatocyte L02 cell line. The profile of gene expression, microRNA (miRNA) and DNA methylation were detected through high-throughput sequencing. Compared with control group, the expression of 826 genes and 187 miRNAs changed significantly in MC-LR treated group...
June 1, 2018: Toxicology Letters
Marie-Charlotte Meinsohn, Fanny Morin, Kalyne Bertolin, Raj Duggavathi, Kristina Schoonjans, Bruce D Murphy
In mouse ovaries, liver receptor homolog-1 [nuclear receptor subfamily 5, group A, member 2 (Nr5a2)] expression is restricted to granulosa cells. Mice with Nr5a2 depletion in this cell population fail to ovulate. To determine whether Nr5a2 is essential for granulosa cell proliferation during follicular maturation, we generated granulosa-specific conditional knockout mice (genotype Nr5a2 floxed Cre-recombinase driven by the anti-Müllerian type II receptor, hereafter cKO) with Nr5a2 depletion from primary follicles forward...
January 1, 2018: Journal of the Endocrine Society
Enhao Fang, Xiuqing Zhang, Qi Wang, Daoming Wang
BACKGROUND: Prostate cancer (PCa) is the most common and the second leading cause of cancer-related death among men in America. As the molecular mechanism of PCa has not yet been completely discovered, identification of hub genes and potential drug of this disease is an important area of research that could provide new insights into exploring the mechanisms underlying PCa. OBJECTIVE: The aim of this study was to identify potential biomarkers and novel drug for prostate cancer treatment...
July 30, 2017: Cancer Biomarkers: Section A of Disease Markers
Jianjun Sha, Wei Xue, Baijun Dong, Jiahua Pan, Xiaorong Wu, Dong Li, Dongming Liu, Yiran Huang
Castration-resistant prostate cancer (CRPC) is an advanced form of prostate cancer. Despite some progresses have been made, the mechanism of CRPC development is still largely unknown, including the genes involved in its development have not been well defined. Here, we identifiedPRKAR2B to be a gene over-expressingin castration-resistant prostate cancer by analyzing the different online databases. Followed functional validation experiments showed that PRKAR2B promoted CRPC cell proliferation and invasion, and inhibited CRPC cell apoptosis...
January 24, 2017: Oncotarget
Jing Su, Wei Wu, Shan Huang, Ruidan Xue, Yi Wang, Yun Wan, Lv Zhang, Lang Qin, Qiongyue Zhang, Xiaoming Zhu, Zhaoyun Zhang, Hongying Ye, Xiaohui Wu, Yiming Li
Obesity has become the most common metabolic disorder worldwide. Promoting brown adipose tissue (BAT) and beige adipose tissue formation, and therefore, a functional increase in energy expenditure, may counteract obesity. Mice lacking type IIβ regulatory subunit of adenosine 3',5' cyclic monophosphate (cAMP)-dependent protein kinase A (PKA-RIIB) display reduced adiposity and resistance to diet-induced obesity. PKA-RIIB, encoded by the Prkar2b gene, is most abundant in BAT and white adipose tissue (WAT) and in the brain...
March 1, 2017: Endocrinology
Hung-Sheng Shang, Jia-You Liu, Hsu-Feng Lu, Han-Sun Chiang, Chia-Hain Lin, Ann Chen, Yuh-Feng Lin, Jing-Gung Chung
Casticin, a polymethoxyflavone, derived from natural plant Fructus Viticis exhibits biological activities including anti-cancer characteristics. The anti-cancer and alter gene expression of casticin on human colon cancer cells and the underlying mechanisms were investigated. Flow cytometric assay was used to measure viable cell, cell cycle and sub-G1 phase, reactive oxygen species (ROS) and Ca(2+) productions, level of mitochondria membrane potential (ΔΨm ) and caspase activity. Western blotting assay was used to detect expression of protein level associated with cell death...
August 2017: Environmental Toxicology
Kevin J Ashton, Melissa E Reichelt, S Jamal Mustafa, Bunyen Teng, Catherine Ledent, Lea M D Delbridge, Polly A Hofmann, R Ray Morrison, John P Headrick
Influences of adenosine 2A receptor (A2A R) activity on the cardiac transcriptome and genesis of endotoxemic myocarditis are unclear. We applied transcriptomic profiling (39 K Affymetrix arrays) to identify A2A R-sensitive molecules, revealed by receptor knockout (KO), in healthy and endotoxemic hearts. Baseline cardiac function was unaltered and only 37 A2A R-sensitive genes modified by A2A R KO (≥1.2-fold change, <5 % FDR); the five most induced are Mtr, Ppbp, Chac1, Ctsk and Cnpy2 and the five most repressed are Hp, Yipf4, Acta1, Cidec and Map3k2...
March 2017: Purinergic Signalling
Zhiming Li, Zaozao Zheng, Jun Ruan, Zhi Li, Xuan Zhuang, Chi-Meng Tzeng
Our previous research suggested that an integrated analysis of microRNA (miRNA) and messenger RNA (mRNA) expression is helpful to explore miRNA-mRNA interactions and to uncover the molecular mechanisms of male infertility. In this study, microarrays were used to compare the differences in the miRNA and mRNA expression profiles in the testicular tissues of severe oligozoospermia (SO) patients with obstructive azoospermia (OA) controls with normal spermatogenesis. Four miRNAs (miR-1246, miR-375, miR-410, and miR-758) and six mRNAs (SLC1A3, PRKAR2B, HYDIN, WDR65, PRDX1, and ADATMS5) were selected to validate the microarray data using quantitative real-time PCR...
August 16, 2016: Oncotarget
Alessandro Del Gobbo, Erika Peverelli, Donatella Treppiedi, Andrea Lania, Giovanna Mantovani, Stefano Ferrero
In this review, we discuss the molecular mechanisms and prognostic implications of the protein kinase A (PKA) signaling pathway in human tumors, with special emphasis on the malignant thyroid. The PKA signaling pathway is differentially activated by the expression of regulatory subunits 1 (R1) and 2 (R2), whose levels change during development, differentiation, and neoplastic transformation. Following the identification of gene mutations within the PKA regulatory subunit R1A (PRKAR1A) that cause Carney complex-associated neoplasms, several investigators have studied PRKAR1A expression in sporadic thyroid tumors...
August 1, 2016: Experimental Cell Research
Sung Han Kim, Jin-Nyoung Ho, Hyunjin Jin, Sang Chul Lee, Sang Eun Lee, Sung-Kyu Hong, Jeong Woo Lee, Eun-Sik Lee, Seok-Soo Byun
PURPOSE: The mechanism of resistance to cisplatin during treatment of bladder cancer (BC) has been a subject of intense investigation in clinical research. This study aims to identify candidate genes associated with resistance to cisplatin, in order to understand the resistance mechanism of BC cells to the drug, by combining the use of microarray profiling, quantitative reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analyses. MATERIALS AND METHODS: The cisplatin sensitive human BC cell line (T24) and the cisplatin resistant BC cell line, T24R2, were used for microarray analysis to determine the differential expression of genes that are significant in cisplatin resistance...
January 2016: Investigative and Clinical Urology
Emmanouil Saloustros, Paraskevi Salpea, Chen-Feng Qi, Lina A Gugliotti, Kitman Tsang, Sisi Liu, Matthew F Starost, Herbert C Morse, Constantine A Stratakis
BACKGROUND: Protein kinase A (PKA) is a holoenzyme that consists of a dimer of regulatory subunits and two inactive catalytic subunits that bind to the regulatory subunit dimer. Four regulatory subunits (RIα, RIβ, RIIα, RIIβ) and four catalytic subunits (Cα, Cβ, Cγ, Prkx) have been described in the human and mouse genomes. Previous studies showed that complete inactivation of the Prkar1a subunit (coding for RIα) in the germline leads to embryonic lethality, while Prkar1a-deficient mice are viable and develop schwannomas, thyroid, and bone neoplasms, and rarely lymphomas and sarcomas...
November 25, 2015: Journal of Experimental & Clinical Cancer Research: CR
Junseong Park, Jungsul Lee, Chulhee Choi
In the post-genomic era, many researchers have taken a systematic approach to identifying abnormal genes associated with various diseases. However, the gold standard has not been established, and most of these abnormalities are difficult to be rehabilitated in real clinical settings. In addition to identifying abnormal genes, for a practical purpose, it is necessary to investigate abnormality diversity. In this context, this study is aimed to demonstrate simply restorable genes as useful drug targets. We devised the concept of "drug targetability" to evaluate several different modes of abnormal genes by predicting events after drug treatment...
2015: Scientific Reports
Sisi Liu, Emmanouil Saloustros, Edward L Mertz, Kitman Tsang, Matthew F Starost, Paraskevi Salpea, Fabio R Faucz, Eva Szarek, Maria Nesterova, Sergey Leikin, Constantine A Stratakis
Carney Complex (CNC), a human genetic syndrome predisposing to multiple neoplasias, is associated with bone lesions such as osteochondromyxomas (OMX). The most frequent cause for CNC is PRKAR1A deficiency; PRKAR1A codes for type-I regulatory subunit of protein kinase A (PKA). Prkar1a(+/-) mice developed OMX, fibrous dysplasia-like lesions (FDL) and other tumors. Tumor tissues in these animals had increased PKA activity due to an unregulated PKA catalytic subunit and increased PKA type II (PKA-II) activity mediated by the PRKAR2A and PRKAR2B subunits...
November 1, 2015: Human Molecular Genetics
Florian Christoph Sigloch, Ulrike Christina Burk, Martin Lothar Biniossek, Thomas Brabletz, Oliver Schilling
Expression of miR-200c is a molecular switch to determine cellular fate towards a mesenchymal or epithelial phenotype. miR-200c suppresses the early steps of tumor progression by preventing epithelial-mesenchymal transition (EMT) and intravasation of tumor cells. Unraveling the underlying molecular mechanisms might pinpoint to novel therapeutic options. To better understand these mechanisms it is crucial to identify targets of miR-200c. Here, we employ a combination of quantitative proteomic and bioinformatic strategies to identify novel miR-200c targets...
September 15, 2015: Oncotarget
Roman Saternus, Stefan Pilz, Stefan Gräber, Marcus Kleber, Winfried März, Thomas Vogt, Jörg Reichrath
Vitamin D deficiency is common in the Caucasian population and is associated with increased incidence and unfavorable outcome of many diseases, including various types of cancer, infectious, cardiovascular, and autoimmune diseases. Individual factors that predispose for a person's vitamin D status, such as skin type, have been identified, but limited data exist on genetic determinants of serum 25-hydroxyvitamin D (25[OH]D) concentration. We have tested the hypothesis that variants of genes (single nucleotide polymorphisms [SNPs]) involved in skin pigmentation are predictive of serum 25(OH)D levels...
January 2015: Endocrinology
Stefano Ferrero, Valentina Vaira, Alessandro Del Gobbo, Leonardo Vicentini, Silvano Bosari, Paolo Beck-Peccoz, Giovanna Mantovani, Anna Spada, Andrea G Lania
The four regulatory subunits (R1A, R1B, R2A, R2B) of protein kinase A (PKA) are differentially expressed in several cancer cell lines and exert distinct roles in both cell growth and cell differentiation control. Mutations of the PRKAR1A gene have been found in patients with Carney complex and in a minority of sporadic anaplastic thyroid carcinomas. The aim of the study was to retrospectively evaluate the expression of different PKA regulatory subunits in benign and non benign human thyroid tumours and to correlate their expression with clinical phenotype...
April 2015: Histology and Histopathology
Monique Tomazele Rovani, Bernardo Garziera Gasperin, Gustavo Freitas Ilha, Rogério Ferreira, Rodrigo Camponogara Bohrer, Raj Duggavathi, Vilceu Bordignon, Paulo Bayard Dias Gonçalves
BACKGROUND: Estradiol (E2) receptors mediate E2 effects on cell proliferation and apoptosis under normal and pathological conditions. However, the mechanisms involved in E2 signaling are not completely understood. The objectives in this study were to evaluate the expression of estrogen receptors (ESRs) during follicular selection in cattle, and the effect of intrafollicular injection of fulvestrant (an antagonist of ESRs) on follicular development and transcript abundance in granulosa cells...
2014: Journal of Ovarian Research
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