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https://www.readbyqxmd.com/read/29297493/the-genomics-of-prostate-cancer-emerging-understanding-with-technologic-advances
#1
Mark A Rubin, Francesca Demichelis
With the advent of next-generation sequencing technologies and large whole-exome and genome studies in prostate and other cancers, our understanding of the landscape of genomic alterations has dramatically been refined. In additional to well-known alterations in genomic regions involving 8p, 8q, 10q23, common ETS translocations and androgen receptor amplifications, newer technology have uncovered recurrent mutations in SPOP, FOXA1, MED12, IDH and complex large scale genomic alterations (eg, chromoplexy). This review surveys the enhanced landscape of genomic alterations in clinically localized and advanced prostate cancer...
January 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29297384/upregulation-of-neto2-gene-in-colorectal-cancer
#2
Maria S Fedorova, Anastasiya V Snezhkina, Elena A Pudova, Ivan S Abramov, Anastasiya V Lipatova, Sergey L Kharitonov, Asiya F Sadritdinova, Kirill M Nyushko, Kseniya M Klimina, Mikhail M Belyakov, Elena N Slavnova, Nataliya V Melnikova, Maria A Chernichenko, Dmitry V Sidorov, Marina V Kiseleva, Andrey D Kaprin, Boris Y Alekseev, Alexey A Dmitriev, Anna V Kudryavtseva
BACKGROUND: Neuropilin and tolloid-like 2 (NETO2) is a single-pass transmembrane protein that has been shown primarily implicated in neuron-specific processes. Upregulation of NETO2 gene was also detected in several cancer types. In colorectal cancer (CRC), it was associated with tumor progression, invasion, and metastasis, and seems to be involved in epithelial-mesenchymal transition (EMT). However, the mechanism of NETO2 action is still poorly understood. RESULTS: We have revealed significant increase in the expression of NETO2 gene and deregulation of eight EMT-related genes in CRC...
December 28, 2017: BMC Genetics
https://www.readbyqxmd.com/read/29272997/genome-variation-and-conserved-regulation-identify-genomic-regions-responsible-for-strain-specific-phenotypes-in-rat
#3
David Martín-Gálvez, Denis Dunoyer de Segonzac, Man Chun John Ma, Anne E Kwitek, David Thybert, Paul Flicek
BACKGROUND: The genomes of laboratory rat strains are characterised by a mosaic haplotype structure caused by their unique breeding history. These mosaic haplotypes have been recently mapped by extensive sequencing of key strains. Comparison of genomic variation between two closely related rat strains with different phenotypes has been proposed as an effective strategy for the discovery of candidate strain-specific regions involved in phenotypic differences. We developed a method to prioritise strain-specific haplotypes by integrating genomic variation and genomic regulatory data predicted to be involved in specific phenotypes...
December 22, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29260398/integrated-bioinformatics-analysis-of-potential-biomarkers-for-prostate-cancer
#4
Jiufeng Tan, Xuefei Jin, Kaichen Wang
The aim was to expound the pathogenesis of prostate cancer and to identify the potentially biomarkers for prostate cancer (PC). DNA methylation microarray data GSE38240 containing 8 prostate cancer metastases and 4 normal prostate samples as well as gene expression profile data GSE26910 containing 6 prostate primary tumors and 6 normal samples were used. Differentially expressed genes (DEGs) and differently methylated sites of PC were screened and the regulatory network was constructed with DEGs-related transcription factors (TFs)...
December 19, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29208003/foxa1-inhibits-hepatocellular-carcinoma%C3%A2-progression-by-suppressing-pik3r1-expression-in-male-patients
#5
Shujiao He, Junyi Zhang, Wan Zhang, Fengsheng Chen, Rongcheng Luo
BACKGROUND: Forkhead box A1 (FOXA1) expression is associated with various types of tumors; however, the function and underlying mechanism of FOXA1 in the development of hepatocellular carcinoma (HCC) remains obscure. METHODS: Here, we investigated the role of FOXA1 in the development of HCC by applying gene function gain and loss analysis to HepG2 and Hep3B cell lines, and comparing outcomes with those of clinical HCC samples. RESULTS: Phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), which encodes protein PI3Kp85 (p85), was identified as a FOXA1 target gene...
December 6, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29180470/er-alpha-binding-by-transcription-factors-nfib-and-ybx1-enables-fgfr2-signalling-to-modulate-estrogen-responsiveness-in-breast-cancer
#6
Thomas M Campbell, Mauro Aa Castro, Kelin Gonçalves deOliveira, Bruce Aj Ponder, Kerstin B Meyer
Two opposing clusters of transcription factors (TF) have been associated with the differential risks of estrogen receptor positive or negative breast cancers, but the mechanisms underlying the opposing functions of the two clusters are undefined. In this study, we identified NFIB and YBX1 as novel interactors of the estrogen receptor alpha (ESR1). NFIB and YBX1 are both risk TF associated with progression of ESR1-negative disease. Notably, they both interacted with the ESR1-FOXA1 complex and inhibited the transactivational potential of ESR1...
November 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/29155818/snail1-mediated-downregulation-of-foxa-proteins-facilitates-the-inactivation-of-transcriptional-enhancer-elements-at-key-epithelial-genes-in-colorectal-cancer-cells
#7
Sabine Jägle, Hauke Busch, Vivien Freihen, Sven Beyes, Monika Schrempp, Melanie Boerries, Andreas Hecht
Phenotypic conversion of tumor cells through epithelial-mesenchymal transition (EMT) requires massive gene expression changes. How these are brought about is not clear. Here we examined the impact of the EMT master regulator SNAIL1 on the FOXA family of transcription factors which are distinguished by their particular competence to induce chromatin reorganization for the activation of transcriptional enhancer elements. We show that the expression of SNAIL1 and FOXA genes is anticorrelated in transcriptomes of colorectal tumors and cell lines...
November 20, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29137314/lack-of-both-androgen-receptor-and-forkhead-box-a1-foxa1-expression-is-a-poor-prognostic-factor-in-estrogen-receptor-positive-breast-cancers
#8
Seho Park, Eunjin Koh, Ja Seung Koo, Seung Il Kim, Byeong-Woo Park, Kyung-Sup Kim
The present study aimed to examine the associations between androgen receptor (AR) and forkhead box A1 (FOXA1) and to investigate clinicopathological features and survival according to both biomarker status in estrogen receptor (ER)-positive breast cancers using in vitro study, patient cohort data, and the cBioPortal for Cancer Genomics and Kaplan-Meier Plotter websites. Experiments using T47D and ZR75-1 demonstrated AR-overexpressing cell lines decreased in cell proliferation through downregulation of ER, but FOXA1 did not change...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29129808/overexpression-of-foxa1-inhibits-cell-proliferation-and-emt-of-human-gastric-cancer-ags-cells
#9
Mengxin Lin, Jie Pan, Qiang Chen, Zongbin Xu, Xiaoyan Lin, Chunmei Shi
The lack of effective medical treatment for advanced stages of gastric cancer mainly contributes to the high mortality rate. The association of forkhead box protein A1 (FOXA1) with tumor progression has been reported in different human cancers. However, the function of FOXA1 in gastric cancer is largely unknown. In the present study, FOXA1 protein showed a significant reduction in gastric cancer samples comparing with matched control samples. In addition, the higher expression of FOXA1 in transcription level was observed in gastric cancer cell lines as compared with that in normal gastric cell line, while the contrary result was observed in protein level...
November 9, 2017: Gene
https://www.readbyqxmd.com/read/29123100/dna-methylation-at-enhancers-identifies-distinct-breast-cancer-lineages
#10
Thomas Fleischer, Xavier Tekpli, Anthony Mathelier, Shixiong Wang, Daniel Nebdal, Hari P Dhakal, Kristine Kleivi Sahlberg, Ellen Schlichting, Anne-Lise Børresen-Dale, Elin Borgen, Bjørn Naume, Ragnhild Eskeland, Arnoldo Frigessi, Jörg Tost, Antoni Hurtado, Vessela N Kristensen
Breast cancers exhibit genome-wide aberrant DNA methylation patterns. To investigate how these affect the transcriptome and which changes are linked to transformation or progression, we apply genome-wide expression-methylation quantitative trait loci (emQTL) analysis between DNA methylation and gene expression. On a whole genome scale, in cis and in trans, DNA methylation and gene expression have remarkably and reproducibly conserved patterns of association in three breast cancer cohorts (n = 104, n = 253 and n = 277)...
November 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/29115609/microrna%C3%A2-212-inhibits-the-proliferation-and-invasion-of-human-renal-cell-carcinoma-by-targeting-foxa1
#11
Zhigang Tong, Xianfeng Meng, Jinsong Wang, Lixin Wang
MicroRNA‑212 (miR‑212) has been observed to be significantly deregulated in various types of human cancer. However, the clinical significance of miR‑212 and the associated molecular signaling pathways involved in the progression of renal cell carcinoma (RCC) remain unclear. In the present study, miR‑212 expression was significantly downregulated in RCC tissues compared with adjacent non‑tumor tissues. Clinical association analysis indicated that low expression of miR‑212 was prominently associated with large tumor size, advanced tumor, nodes, metastasis stage and lymph node metastasis...
January 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115441/role-of-transcription-factor-foxa1-in-non%C3%A2-small-cell-lung-cancer
#12
Jia Li, Shirong Zhang, Lucheng Zhu, Shenglin Ma
In our previous study, stable subpopulations of the A549 lung cancer cell line with high/low invasive potential (H/L‑INV) were obtained. In the present study, microarray analysis of the H/L‑INV A549 subpopulations was performed to evaluate genes associated with high invasiveness. Forkhead box protein A1 (FOXA1) was selected for further investigation. The expression levels of FOXA1 in the primary lesion and metastatic lymph nodes were assessed using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29108194/-microrna-30a-inhibits-proliferation-of-hepatocellular-carcinoma-cells-via-targeted-regulation-of-forkhead-box-protein-a1
#13
Y Li, L Fu, X Y Fu, R H Li, S F Peng
Objective: To investigate the expression of microRNA-30a (miR-30a) in hepatocellular carcinoma (HCC) and related molecular mechanisms in regulating HCC cell proliferation. Methods: A total of 30 pairs of HCC and adjacent tissue samples were collected, and quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression of forkhead-box protein A1 (FOXA1). Methyl thiazolyl tetrazolium (MTT) assay was used to evaluate the proliferation of HCC cells, luciferase reporter gene assay was performed to verify the target relationship between miR-30a and FOXA1, and MTT assay and Western blot were used to measure the proliferation of HepG2 cells and the protein expression of FOXA1 after miR-30a transfection...
September 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29093522/genome-wide-discovery-of-long-intergenic-noncoding-rnas-and-their-epigenetic-signatures-in-the-rat
#14
Aimin Li, Zhong-Yin Zhou, Xinhong Hei, Newton O Otecko, Junying Zhang, Yajun Liu, Hongfang Zhou, Zhiqiang Zhao, Lei Wang
Long intergenic noncoding RNAs (lincRNAs) play a crucial role in many biological processes. The rat is an important model organism in biomedical research. Recent studies have detected rat lincRNA genes from several samples. However, identification of rat lincRNAs using large-scale RNA-seq datasets remains unreported. Herein, using more than 100 billion RNA-seq reads from 59 publications together with RefSeq and UniGene annotated RNAs, we report 39,154 lincRNA transcripts encoded by 19,162 lincRNA genes in the rat...
November 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29072684/plod2-regulated-by-transcription-factor-foxa1-promotes-metastasis-in-nsclc
#15
Hongzhi Du, Yulong Chen, Xiaoying Hou, Yue Huang, Xiaohui Wei, Xiaowen Yu, Shuyun Feng, Yao Wu, Meixiao Zhan, Xin Shi, Sensen Lin, Ligong Lu, Shengtao Yuan, Li Sun
In multiple types of tumors, fibrotic collagen is regarded as the 'highway' for cancer cell migration, which is mainly modified by lysyl hydroxylase 2 (PLOD2). The previous findings have demonstrated that the expression of PLOD2 was regulated by multiple factors, including HIF-1α, TGF-β and microRNA-26a/b. Although PLOD2 was confirmed to be related to poor prognosis in lung adenocarcinoma, the regulatory mechanism and function of PLOD2 in human lung adenocarcinoma is poorly understood. On the other hand, upregulation or hyperactivation of epidermal growth factor receptor is considered as a prognostic marker in many cancers, especially in non-small-cell lung cancer (NSCLC)...
October 26, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29029032/foxa1-expression-is-a-strong-independent-predictor-of-early-psa-recurrence-in-erg-negative-prostate-cancers-treated-by-radical-prostatectomy
#16
Maria Christina Tsourlakis, Agapi Eleftheriadou, Annegret Stender, Philipp Weigand, Katharina Grupp, Claudia Hube-Magg, Martina Kluth, Cornelia Schroeder, Stefan Steurer, Andrea Hinsch, Andreas Luebke, Alexander Angerer, Corinna Wittmer, Emily Friedrich, Cosima Göbel, Franziska Büscheck, Hans Heinzer, Markus Graefen, Ronald Simon, Guido Sauter, Waldemar Wilczak, Sarah Minner, Thorsten Schlomm, Frank Jacobsen
FOXA1 is a transcription factor involved in androgen signaling with relevance for lineage specific gene expression of the prostate. The expression was analyzed by immunohistochemistry on a tissue microarray containing 11,152 prostate cancer specimens. Results were compared to tumor phenotype, biochemical recurrence, androgen receptor expression, ERG status and other recurrent genomic alterations. FOXA1 expression was detectable in 97.6% of 8,227 interpretable cancers and considered strong in 28.5%, moderate in 46...
September 26, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28943920/clinical-predictors-of-pathological-complete-response-to-neoadjuvant-chemotherapy-in-triple-negative-breast-cancer
#17
Ayako Nakashoji, Akira Matsui, Aiko Nagayama, Yuko Iwata, Manami Sasahara, Yuya Murata
The response of triple-negative breast cancer (TNBC) to chemotherapy is heterogeneous; particular subtype classifications based on mRNA gene expression analysis have been demonstrated to be associated with a pathological complete response (pCR). The aim of the present study was to investigate additional clinical and pathological characteristics associated with pCR status. The pathological and clinical characteristics of 40 TNBC patients who underwent neoadjuvant chemotherapy followed by surgery were retrospectively analyzed by dividing the cases into two groups according to the response to treatment: pCR (n=12) and non-pCR (n=28)...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28938408/pioneer-factors-foxa1-and-foxa2-assist-selective-glucocorticoid-receptor-signaling-in-human-endometrial-cells
#18
Shannon Whirledge, Edwina P Kisanga, Robert N Taylor, John A Cidlowski
Successful pregnancy relies on dynamic control of cell signaling to achieve uterine receptivity and the necessary biological changes required for endometrial decidualization, embryo implantation, and fetal development. Glucocorticoids are master regulators of intracellular signaling and can directly regulate embryo implantation and endometrial remodeling during murine pregnancy. In immortalized human uterine cells, we have shown that glucocorticoids and estradiol (E2) coregulate thousands of genes. Recently, glucocorticoids and E2 were shown to coregulate the expression of Left-right determination factor 1 (LEFTY1), previously implicated in the regulation of decidualization...
November 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938404/the-transcriptome-of-estrogen-independent-mammary-growth-in-female-mice-reveals-that-not-all-mammary-glands-are-created-equally
#19
COMPARATIVE STUDY
Grace E Berryhill, Danielle G Lemay, Josephine F Trott, Lucila Aimo, Adam L Lock, Russell C Hovey
Allometric growth of ducts in the mammary glands (MGs) is widely held to be estrogen dependent. We previously discovered that the dietary fatty acid trans-10, cis-12 conjugated linoleic acid (CLA) stimulates estrogen-independent allometric growth and terminal end bud formation in ovariectomized mice. Given the similar phenotype induced by estrogen and CLA, we investigated the shared and/or divergent mechanisms underlying these changes. We confirmed MG growth induced by CLA is temporally distinct from that elicited by estrogen...
October 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28927002/predicting-variation-of-dna-shape-preferences-in-protein-dna-interaction-in-cancer-cells-with-a-new-biophysical-model
#20
Kirill Batmanov, Junbai Wang
DNA shape readout is an important mechanism of transcription factor target site recognition, in addition to the sequence readout. Several machine learning-based models of transcription factor-DNA interactions, considering DNA shape features, have been developed in recent years. Here, we present a new biophysical model of protein-DNA interactions by integrating the DNA shape properties. It is based on the neighbor dinucleotide dependency model BayesPI2, where new parameters are restricted to a subspace spanned by the dinucleotide form of DNA shape features...
September 18, 2017: Genes
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