bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1941: Plasma levels of miRNA-155 as a powerful diagnostic marker for dedifferentiated liposarcoma
Authors: Boro Aleksandar , Bauer David , Born Walter , Fuchs Bruno 
Published: July 2016

Abstract
PURPOSE: Atypic lipomatous tumors (ALT) and dedifferentiated liposarcomas (DDLS) are closely related liposarcoma subtypes, often difficult to distinguish but they exhibit an entirely different clinical outcome. Recently discovered regulatory functions of miRNAs in liposarcoma progression prompted us to investigate miRNAs as potential diagnostic biomarkers in liposarcoma with a main focus on circulating miRNAs for fast and reliable differential diagnosis.
PATIENTS AND METHODS: Tumor and blood samples of 35 patients with lipomatous lesions collected between June 2011 and September 2014 were analyzed by qRT-PCR. They included 10 lipomas, 7 ALT, 5 DDLS and 13 myxoid liposarcomas (MLS). Ten samples of normal fat tissue and blood from 20 healthy volunteers were used as controls.
RESULTS: A meta-analysis of public data on miRNA expression in liposarcoma revealed 9 miRNAs with potential diagnostic power. Out of these, miRNA-155 was found significantly elevated in the circulation of DDLS patients as compared to the plasma levels detected in all other liposarcoma subtypes and in healthy subjects. miRNA-155 levels in the plasma samples correlated significantly (r = 0.41,p = 0.02) with those in corresponding tumor extracts. This correlation was even more pronounced in an analysis of plasma and tumor extracts of malignant liposarcoma subtypes alone (r = 0.51,p = 0.02). Receiver operating characteristic analysis indicated that plasma miRNA-155 levels have a high diagnostic accuracy for distinguishing DDLS from healthy subjects (AUC = 0.91,p = 0.005) and from lipomas (AUC = 0.86,p = 0.02), MLS (AUC = 0.92,p = 0.006) and most importantly ALT (AUC = 0.91,p = 0.01) patients.
CONCLUSION: In conclusion, this study identified miRNA-155 as a first blood biomarker for the differential diagnosis of DDLS.
Citation Format: Aleksandar Boro, David Bauer, Walter Born, Bruno Fuchs. Plasma levels of miRNA-155 as a powerful diagnostic marker for dedifferentiated liposarcoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1941.
Abstract 1965: CRISPR/cas9, an innovative genomic tool to knock down microRNA
Authors: Chang Hong , Yi Bin , Ma Ruixia , Zhao Hongyou , Xi Yaguang 
Published: July 2016

Abstract
MicroRNAs are a set of small and non-coding RNA molecules showing the “master” role in regulation of coding-gene expression at the post-transcriptional/translational levels. Several methods have been developed for microRNA loss-of-function study, such as antisense inhibitors and sponges; however, their robustness, specificity, and stability cannot be highly satisfied with the increased demand on microRNA functional research. CRISPR/cas9 system is emerging as a novel genome editing tool that has been exclusively studied in coding-genes knockdown, but its indication in microRNA research has not been explored yet. In this project, we clone CRISPR/cas9 constructs with designated single guide RNAs targeting biogenesis processing sites of the selected microRNAs, miR-200b and miR-17. Our results demonstrate that CRISPR/cas9 can robustly reduce the expression of these microRNAs up to 96%. More significantly, our data support high specificity and low off-target effect of CRISPR/cas9 in editing microRNA genes. Given this feature, it possesses an advantage to knockdown microRNAs in same family or with highly conserved sequences superior to antisense inhibitors and sponges. In addition, for the first time, we demonstrate the long term stability of microRNA knockdown phenotype by CRISPR/cas9 in both in vitro and in vivo models. In conclusion, we develop a novel method by adapting CRISPR/cas9 system to downregulate microRNA expression, which shows improved robustness, specificity, and stability than the previously established methodologies.
Citation Format: Hong Chang, Bin Yi, Ruixia Ma, Hongyou Zhao, Yaguang Xi. CRISPR/cas9, an innovative genomic tool to knock down microRNA. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1965.
Abstract 1968: Systematic validation of microRNA based prognostic biomarkers for stage II, III and IV colorectal cancer
Authors: Ma Dongling , Xue Yaqi , Fesler Andrew , Zhai Haiyan , Yang Jie , Ieamniramit Apisri , Li Wenzhe , Ju Jingfang 
Published: July 2016

Abstract
microRNA (miRNA) based biomarkers have great potential due to their critical regulatory functions, superior stability, and relative small number compared to mRNAs. We have previously discovered a number of miRNAs that play key roles in colon cancer stem cell resistance and demonstrated their clinical potential as prognostic biomarkers. In this study, we have validated the prognostic potential of a panel of miRNAs in 204 stage II, III, and IV colorectal cancer specimens by qRT-PCR analysis. Many of the miRNAs have been functionally validated to be important in contributing to chemoresistance to 5-FU based chemotherapy. We also determined that miR-16 is the most consistent miRNA for expression normalization. We have validated several miRNAs that are significantly associated with disease free survival (DFS) and overall survival (OS) of stage II, III and IV colorectal cancer patients. This study, together with some of the previous studies, establishes a solid foundation for miRNA based precision management of colorectal cancer.
Citation Format: Dongling Ma, Yaqi Xue, Andrew Fesler, Haiyan Zhai, Jie Yang, Apisri Ieamniramit, Wenzhe Li, Jingfang Ju. Systematic validation of microRNA based prognostic biomarkers for stage II, III and IV colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1968.
Abstract 197: Phospholipids regulate the localization and oncogenic potential of protein tyrosine kinase 6 in prostate cancer
Authors: Wozniak Darren J. , Hitchinson Ben , Bie Wenjun , Gaponenko Vadim , Tyner Angela L. 
Published: July 2016

Abstract
Background: Protein tyrosine kinase 6 (PTK6, also called BRK) is an intracellular SRC-related tyrosine kinase that does not possess canonical localization signals. Lack of targeting yields flexibility in its intracellular localization and access to substrates. PTK6 is observed in the nuclei of prostate epithelial cells where it promotes differentiation and inhibits growth. PTK6 is activated at the plasma membrane in PTEN-deficient mouse prostate tumors where the concentration of PIP3 is high due to PTEN loss of function. Membrane-associated PTK6 induces cell transformation, the epithelial-mesenchymal transition, and tumor cell metastasis. In human prostate cancer, active PTK6 associates with the plasma membrane and its increased expression correlates with metastasis and poor survival. Our studies aimed to characterize how the mislocalization and activation of PTK6 in prostate cancer is regulated.
Results: Based on our observation that loss of PTEN induces accumulation of PTK6 at the membrane, we hypothesized that PTK6 binds to the plasma membrane secondary messenger phosphatidylinositol (3,4,5)-trisphosphate (PIP3). Amino acid sequence alignment predicts H52, Y53, and K54 of PTK6 as a potential PIP3 binding site, which resembles the lipid-binding HYK domain of tyrosine kinases BTK and Abl. Using NMR saturation transfer difference (STD) experiment, we observed that the SH2 domain of PTK6 contains a binding site for inositol trisphosphate (IP3) a soluble PIP3 mimic. As predicted, statistical analysis identified Y53 of the PTK6 HYK motif within the SH2 domain as a residue with substantial chemical shift perturbations (CSPs) induced by independent titrations with PIP3 analogs IP3, IP4, and 1,2-dihexanoyl PIP3 in 15N HSQC, as compared to controls. Using autophosphorylated and unphosphorylated PTK6, NMR STD experiments show that only active (pY342) PTK6 binds to IP3. Treatment of prostate cancer cells with the PI3K inhibitor wortmannin reduces active PTK6 at the plasma membrane.
Conclusions: Our data demonstrate that active PTK6 is recruited to the plasma membrane through direct interactions with PIP3. Membrane association places PTK6 in close proximity to its oncogenic substrates AKT, FAK and BCAR1, thereby promoting tumor progression. These findings may facilitate identification of novel PTK6 inhibitors that block its association with the membrane, while not affecting its tumor suppressive role in the nucleus.
This work is funded by NIH grant 1R01CA188427 to ALT and VG.
Citation Format: Darren J. Wozniak, Ben Hitchinson, Wenjun Bie, Vadim Gaponenko, Angela L. Tyner. Phospholipids regulate the localization and oncogenic potential of protein tyrosine kinase 6 in prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 197.
Abstract 1982: BRD4-FOXO axis maintains differentiated mammary epithelial phenotype by regulating p63 and GRHL3 expression
Authors: Nagarajan Sankari , Bedi Upasana , Budida Anusha , Xie Wanhua , Hamdan Feda Hisham Moh’d , Mishra Vivek Kumar , Najafova Zeynab , Alawi Malik , Indenbirken Daniela , Knapp Stephan , Chiang Cheng-Ming , Grundhoff Adam , Scheel Christina H. , Kari Vijayalakshmi , Wegwitz Florian , Johnsen Steven A. 
Published: July 2016

Abstract
Bromodomain-containing protein 4 (BRD4) is an important epigenetic reader which promotes gene transcription to modulate cell-specific functions and is under intensive investigation for its potential as an anti-tumor therapeutic target. However, the role of BRD4 in non-transformed cells remains unclear. Using RNA sequencing and chromatin immunoprecipitation-sequencing analyses in normal basal-like breast epithelial cells, we demonstrate that BRD4 is required for the expression of epithelial-specific genes and suppression of stem cell-like properties by binding to the distal regions of epithelial-related genes. Moreover, BRD4 occupancy correlates with enhancer activity and enhancer RNA (eRNA) transcription of these genes. Interestingly, we show that BRD4 perturbation regulates the expression of p63 and Grainy Head-like transcription factor-3, GRHL3, whose depletion partially mimics BRD4 inhibition and impairs a differentiated phenotype. By binding to the distal regions of p63 and GRHL3, BRD4 promotes RNA polymerase-II occupancy and thus affects eRNA transcription. Motif analyses on cell-specific BRD4 binding sites predict the involvement of FOXO transcription factors. Consistently, inhibition of EGFR-AKT signalling activates FOXO1 function and promotes the expression of p63 and GRHL3. Activation of Src kinase signaling decreases RNA polymerase-II occupancy on BRD4 target genes and enhancers. Altogether, these findings provide evidence that BRD4 promotes a differentiated epithelial phenotype in non-transformed mammary cells at least in part through the activation of p63 and GRHL3 expression by associating with FOXO factors.
Citation Format: Sankari Nagarajan, Upasana Bedi, Anusha Budida, Wanhua Xie, Feda Hisham Moh’d Hamdan, Vivek Kumar Mishra, Zeynab Najafova, Malik Alawi, Daniela Indenbirken, Stephan Knapp, Cheng-Ming Chiang, Adam Grundhoff, Christina H. Scheel, Vijayalakshmi Kari, Florian Wegwitz, Steven A. Johnsen. BRD4-FOXO axis maintains differentiated mammary epithelial phenotype by regulating p63 and GRHL3 expression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1982.
Abstract 1985: Oncogenic activation of RNA binding proteins and c-Myc signaling in hepatocellular carcinoma
Authors: Hien Dang T. , Takai Atsushi , Forgues Marshonna , Wang Xin Wei 
Published: July 2016

Abstract
Global transcriptomic alterations of both coding and non-coding RNA species are a ubiquitous feature associated with human cancers including hepatocellular carcinoma (HCC). Dysregulation of RNA-binding proteins (RBPs), the key regulators of RNA processing, is one mechanism in which cancer cells select to promote tumorigenesis. We analyzed genomic alterations amongst a family of more than 800 mRNA RBPs (mRBPs) in 1,225 clinical specimens from HCC patients and found that RBPs are significantly activated through gene amplification in a subset of tumors with poor prognosis, suggesting their potential oncogenic roles in HCC progression. Amongst the top candidates, RD binding protein (RDBP) was further characterized for its oncogenic role and effects on the HCC transcriptome. While the activation of RDBP induced an oncogenic phenotype, the abrogation of RDBP in HCC cells significantly decreased cancer associated phenotypes such as cell proliferation, migration/invasion and tumorigenicity in vivo. Further analyses revealed that RDBP-dependent genes were tumor-related with a significant enrichment for c-Myc targets, suggesting interplay between RDBP and c-Myc signaling. Similar data were also found in HCC clinical specimens where c-Myc amplification was uncommon. Consistently, the RDBP-dependent c-Myc target gene signature was able to predict HCC patient survival in two independent cohorts of more than 400 patients. Our results demonstrate that oncogenic activation of RDBP is a novel mechanism that contributes to global transcriptome imbalance, which is selective for the activation of c-Myc oncogenic signaling in HCC. Concurrent with the current model that indicates that c-Myc can promote tumorigenesis through transcription dysregulation, our current work suggests that therapies focused on targeting RDBP may be valuable for clinical treatment of many different tumors with activated c-Myc signaling, including HCC.
Citation Format: Dang T. Hien, Atsushi Takai, Marshonna Forgues, Xin Wei Wang. Oncogenic activation of RNA binding proteins and c-Myc signaling in hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1985.
Abstract 2: Metabolomics analysis reveals distinct profiles of non-muscle invasive and muscle-invasive bladder cancer
Authors: Sahu Divya , Lotan Yair , Wittmann Bryan , Neri Bruce , Hansel Donna 
Published: July 2016

Abstract
Background: Bladder cancer affects &gt;70,000 patients annually in the United States. Despite its high incidence, therapeutic options are limited in early or late stage. We wanted to identify key metabolic pathways that were altered in bladder cancer development and progression.
Experimental Design: We performed global metabolomics profiling of benign urothelium, high-grade non-muscle invasive bladder cancer and advanced, muscle-invasive bladder cancer using GC-MS and LC-MS platforms. This analysis was coupled with publicly available data on transcriptomics of key enzymes, to determine pathways that may be suitable for future therapeutics development.
Results: Categorical pathways globally dysregulated in cancer relative to benign urothelium included glucose, TCA cycle, lipid, amino acid and nucleotide pathways. Bladder cancers demonstrated Warburg metabolism, with elevated glucose utilization to
drive glycolysis and sorbitol pathway intermediates. Elevated late TCA cycle intermediates, coupled with higher levels of amino acids and dipeptides, suggest the possibility of anaplerotic activity in bladder cancer as a mechanism to sustain energy production. Medium and long chain fatty acids were produced at the expense of dicarboxylic fatty acids. Muscle-invasive bladder cancers showed enhanced use of COX and LOX metabolomics pathways and a possible role for inflammation in regulating NAD+ synthesis in muscle-invasive bladder cancer. Transcriptomic profiling validated that the majority of metabolomics pathway alterations corresponded to gene expression changes of enzymes responsible for metabolite production.
Conclusions: This study identifies multiple parallel metabolomics changes unique to non-muscle invasive and muscle-invasive bladder cancer that can be used to justify testing novel therapeutics targeting metabolic pathways in bladder cancer.
Citation Format: Divya Sahu, Yair Lotan, Bryan Wittmann, Bruce Neri, Donna Hansel. Metabolomics analysis reveals distinct profiles of non-muscle invasive and muscle-invasive bladder cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2.
Abstract 2001: Elucidate the functions of TBX3 in AR positive prostate cancer
Authors: zhu. sinan 
Published: July 2016

Abstract
TBX3 is a transcriptional repressor belonging to the T-box gene family. It is involved in lineage specification in mammary gland, limb and heart during embryonic development. Mutations in TBX3 can cause ulnar-mammary syndrome, affecting limb, apocrine gland, tooth, hair and genital development. TBX3 is amplified/mutated in a variety of cancers, including melanoma, bladder, breast and prostate cancer. Recent findings suggest there is a strict correlation between estrogen receptor and TBX3 expression in mammary gland and TBX3 is mutated in 9% of invasive lobular breast cancer. However, little is known about the functions of TBX3 in hormone-dependent tumors. Here we screened several AR+ and AR- prostate cancer cell line and we found that the expression of TBX3 and AR is positively correlated. Moreover, in benign human prostate tissue, TBX3 localization is overlapped with that of AR. Knocking down TBX3 by siRNA resulted in decreased cell proliferation and cell cycle arrest in AR+ cell line Lncap and Vcap, but there was no effect on AR- cell line PC3 and DU14 upon TBX3 knock-down. TBX3 ChIP-seq in both Lncap and Vcap revealed co-binding of TBX3, ETS transcriptional factors and FOXA1 on AR targeted genes. Gene Set Enrichment Analysis (GSEA) of RNA-seq data from Lncap cells infected with lentivirus expressing siSCR or siTBX3 indicated that TBX3 suppresses AR and ETV1 signaling. In conclusion, our data suggests that TBX3 is essential for AR+ prostate cancer cell growth and may play a role in regulating androgen signaling.
Citation Format: sinan zhu. Elucidate the functions of TBX3 in AR positive prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2001.
Abstract 2004: Nucleation of transcriptional super-enhancers at tumor oncogenes by small insertions
Authors: Abraham Brian J. , Hnisz Denes , Weintraub Abraham S. , Kwiatkowski Nicholas , Li Charles H. , Rahman Sunniyat , Li Zhaodong , Lee Tong Ihn , Look A Thomas , Mansour Marc , Young Richard A. 
Published: July 2016

Abstract
Transcriptional super-enhancers drive expression of oncogenes in many cancers and are being targeted with novel transcriptional and epigenetic therapeutics[1,2,3,4]. Super-enhancers are acquired by cancers through multiple mechanisms, including DNA translocation of an extant super-enhancer and focal amplification. We recently discovered a novel mechanism by which super-enhancers are nucleated in T cell acute lymphoblastic leukemias (T-ALLs)[5]. In this case, a small, monoallelic insertion creates a DNA binding site for a master transcription factor protein, which binds and recruits additional factors to nucleate the super-enhancer, which in turn drives high levels of the TAL1 oncogene. We describe here a method for unbiased identification of similar genomic insertions that nucleate potentially oncogenic regulatory elements in cancers. This approach uses data from genome-wide ChIP-Seq studies that map locations of enhancer-binding proteins to identify short DNA sequences missing from reference genomes. We have found and catalogued many additional genomic insertions in 80 additional cancers. An additional insertion has been functionally characterized and determined to be a bona fide enhancer-nucleating insertion that exists in patient genomes. I will describe new insights into the regulation of cancer that occur due to nucleation of novel regulatory elements.
[1] Hnisz, Abraham, Lee, et al., Cell 2013
[2] Loven, Hoke, Lin, et al., Cell 2013
[3] Kwiatkowski, et al., Nature, 2014
[4] Wang, et al., Cell, 2015
[5] Mansour et al., Science 2014
Citation Format: Brian J. Abraham, Denes Hnisz, Abraham S. Weintraub, Nicholas Kwiatkowski, Charles H. Li, Sunniyat Rahman, Zhaodong Li, Tong Ihn Lee, A Thomas Look, Marc Mansour, Richard A. Young. Nucleation of transcriptional super-enhancers at tumor oncogenes by small insertions. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2004.
Abstract 2013: The PAX3-FOXO1 oncogene drives aneuploidy and overrides aneuploidy-associated proliferative defects in alveolar rhabdomyosarcoma
Authors: Hollenbach Andrew D. , Loupe Jacob M. , Miller Patrick J. , Bonner Benjamin P. , Maggi Elaine C. , Vijayaraghavan Jyothi , Zabaleta Jovanny , Taylor Christopher M. , Miller Fern , Crabtree Judy S. 
Published: July 2016

Abstract
Alveolar Rhabdomyosarcoma (ARMS) is primarily defined by the t(2;13)(q35;q14) translocation, which generates the PAX3-FOXO1 oncogene. Despite the fact that ARMS are frequently aneuploid, like a majority of other solid tumors, it is unknown whether PAX3-FOXO1 contributes to the development and/or persistence of aneuploidy. In this study we show that PAX3-FOXO1 serves as the driver mutation to promote aneuploidy by globally altering gene regulatory networks essential for maintaining proper chromosome number and structure. Further, we demonstrate that PAX3-FOXO1 overrides aneuploid-dependent growth arrest by altering the expression of growth factor related regulatory networks. Finally, we present evidence that phosphorylation of PAX3-FOXO1 contributes to these gene regulatory network changes. This is the one of the first studies describing how an oncogene and post-translational modifications of the corresponding oncoprotein drive the acquisition of aneuploidy and override proliferation defects in malignant transformation. The mechanism for PAX3-FOXO1 described in this work has implications for other solid tumors where large-scale genomics studies may elucidate how global alterations contribute to tumor phenotypes allowing the development of much needed multi-faceted tumor-specific therapeutic regimens.
Citation Format: Andrew D. Hollenbach, Jacob M. Loupe, Patrick J. Miller, Benjamin P. Bonner, Elaine C. Maggi, Jyothi Vijayaraghavan, Jovanny Zabaleta, Christopher M. Taylor, Fern Miller, Judy S. Crabtree. The PAX3-FOXO1 oncogene drives aneuploidy and overrides aneuploidy-associated proliferative defects in alveolar rhabdomyosarcoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2013.