bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 933: Protein kinase a regulation of malignant brain tumor migration
Authors: Ausland Jennifer N. , Newman Robert H. , Martin Patrick M. 
Published: July 2016

Abstract
Glioblastoma multiforme (GBM) is the most common and deadly type of primary brain tumor, accounting for over 13,000 new cases in the U.S. annually and a two-year survival rate of &lt; 5%. GBMs are highly invasive and classified by the World Health Organization as a grade IV astrocytoma. Recent studies have shown that protein kinase A (PKA), a key regulator of signal transduction and various biological functions, is essential for maintaining polarity during cell migration and that localized activation of PKA at the leading edge is an early event in directional cell migration of other cell types. Though PKA has previously been shown to promote proliferation and migration in lung, colorectal, adrenocortical, and prostate cancer cell lines, the molecular mechanisms that link PKA activity with GBM physiology remain unclear. Wound healing assays in human GBM cell lines U-251 MG, U-87 MG and A172, demonstrated that GBM cell migration increased following the addition of 20 μM epidermal growth factor (EGF). Similar results were found with 5 μM treatment of the adenylate cyclase activator, forskolin, and inhibited by pre-treatment with 10 μM of the PKA inhibitor, H89. In order to assay the amount of PKA activity, we measured the phosphorylation of cAMP response element binding protein (CREB) in these cell lines. Western blot studies revealed an increase in CREB phosphorylation in cells treated with EGF and forskolin. Phosphorylation of CREB was decreased with the addition of H89 treatment. Our western blot analysis supports our wound healing data demonstrating a correlation between increased PKA-mediated CREB phosphorylation and migration in the absence of serum. Taken together, these data suggest that PKA activation by EGF is involved in GBM cell migration. Moreover, our findings describe a mechanism by which PKA regulates the migration of human brain tumors.
Citation Format: Jennifer N. Ausland, Robert H. Newman, Patrick M. Martin. Protein kinase a regulation of malignant brain tumor migration. [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 933.
Abstract 939: Cell-free DNA associated with extracellular vesicle: Biomarker or bioactivity
Authors: Shelke Ganesh V. , Jang Su Chul , Yin Yanan , Lässer Cecilia , Lötvall Jan 
Published: July 2016

Abstract
Extracellular vesicles (EVs) including exosomes transfer bioactive cargo, including proteins and nucleic acids. Recently, EVs associated DNA were shown to be surrogate biomarker present in body fluids harboring various oncogenic mutations. Cell-free, extracellular DNA is reported in cell cultures and many body fluids, but its relative location in relation to EVs and function is not known. Our study demonstrates that DNase sensitive nucleic acids were present on the surface of EV isolates from mast cell lines. Association of EV-DNA was revealed by increase of zeta potential and particle number upon DNase treatment. Additionally, cytoplasmic DNA traces were found in recipient mesenchymal stem cell after EVs treatment. In conclusion, we define that surface association of DNA with EVs that could regulate recipient cellular function.
Citation Format: Ganesh V. Shelke, Su Chul Jang, Yanan Yin, Cecilia Lässer, Jan Lötvall. Cell-free DNA associated with extracellular vesicle: Biomarker or bioactivity. [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 939.
Abstract 945: Tissue tranglutaminase-2 promotes gastric cancer progression via ERK1/2 pathway
Authors: Su Liping , Wang Xiaofeng , Zhou Quan , Wu Xiongyan , Liu Bingya 
Published: July 2016

Abstract
Gastric cancer is one of the most common tumors worldwide with extensive local tumor invasion, metastasis and poor prognosis. Thus, understanding the mechanisms regulating progression of gastric cancer is the key for developing effective therapeutic strategies. Tissue tranglutaminase-2 (TG2), a multifunctional member of the transglutaminase (TGase) family, has already been proved to play an important role in tumor initiation and progression. However, the specific role and underlying molecular mechanisms of TG2 in the progression of gastric cancer (GC) remain unknown. Here we showed that TG2 was highly expressed in GC tissues and positively associated with depth of tumor invasion and late TNM stage. With gain and lose-of function approaches, we found that TG2 promotes GC cell proliferation, migration and invasion, as well as tumorigenesis and peritoneal metastasis in vivo. These events were associated with activating of ERK1/2 pathway, and ERK1/2 inhibitor U0126 inhibited cell proliferation, migration and invasion induced by overexpression of TG2. Taken together, these findings suggest that TG2 contributes to tumorigenesis and progression of GC by activating the ERK1/2 signaling pathway and is a potential therapeutic target of metastatic gastric cancer.
Citation Format: Liping Su, Xiaofeng Wang, Quan Zhou, Xiongyan Wu, Bingya Liu. Tissue tranglutaminase-2 promotes gastric cancer progression via ERK1/2 pathway. [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 945.
Abstract 954: Analysis of noncoding RNA expression in a mouse model of PTEN-deficient prostate cancer
Authors: De Velasco Marco A. , Kura Yurie , Sakai Kazuko , Hatanaka Yuji , Fujita Yoshihiko , Togashi Yosuke , Terashima Masato , Yoshikawa Kazuhiro , Nishio Kazuto , Uemura Hirotsugu 
Published: July 2016

Abstract
Prostate cancer is a heterogeneous disease that is driven by combined genetic and epigenetic alterations. A significant portion of the mammalian genome consists of non-coding regions of RNA. Increasing evidence has shown that these noncoding RNAs (ncRNAs) have significant roles in the epigenetic regulation of several cellular processes, and their dysregulation can contribute to tumorigenesis and promote disease progression in many cancer types. In order to gain better insights into the potential roles of ncRNAs in prostate cancer, we used a genetically engineered mouse model of prostate cancer to perform a comparative analysis of the cancer transcriptome and the landscape of ncRNAs in castration-naïve prostate tumors and the progression to castration-resistant disease. Whole transcription arrays were used to explore both messenger (mRNA) and long intergenic non-coding RNA (LincRNA) transcript expression in normal prostate tissue from wildtype mice and prostate tumors from conditional PTEN-knockout mice. Comparative analyses were performed between prostate tumor samples from castration-naïve mice and, at 4 weeks and 10 weeks post-surgical castration. Altered expression of ncRNAs was most commonly observed and accounted for 56.2% (2370/4216), 47.6% (4460/9366) and 41.57% (1545/3717) of the total genes differentially expressed between normal mouse prostate and prostate tumors from castration-naïve, 4 weeks post-castration and 10 weeks post-castration, respectively. We also profile the expression of relevant cancer-related lincRNAs present in these models. Overall, our analyses provide data to support a role of LincRNA dysregulation in the pathogenesis of PTEN-deficient prostate cancer, and suggest that these mouse models might provide a potential preclinical tool to test candidate prospective therapies targeting ncRNAs.
Citation Format: Marco A. De Velasco, Yurie Kura, Kazuko Sakai, Yuji Hatanaka, Yoshihiko Fujita, Yosuke Togashi, Masato Terashima, Kazuhiro Yoshikawa, Kazuto Nishio, Hirotsugu Uemura. Analysis of noncoding RNA expression in a mouse model of PTEN-deficient 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 954.
Abstract 975: Hypoxic long noncoding RNA NDRG1-OT1 inhibit NDRG1 in MCF-7 breast cancer cell line
Authors: Lin Hsin-Chen , Lai Liang-Chuan , Chen Hsing-Guang , Chen Hung-Hsin , Chang Mei-Hung , Tsai Mong-Hsun , Chung Eric Y. 
Published: July 2016

Abstract
Hypoxia is a crucial factor that associated with solid tumor progression by driving multiple signaling pathway. Our lab previously reported that NDRG1 was oxygen-responsive genes and could affect cellular function in a breast cancer cell line MCF-7. Long-non coding RNAs (lncRNAs) have recently emerged as important regulators of tumor progression by participating in several process of gene expression. However, it is unclear whether lncRNAs are responsed to oxygen concentrations in breast cancer. Therefore, the aim of this study is to identify lncRNAs which are responsive upon changes in oxygen concentrations, and its regulatory mechanism in the breast cancer MCF-7 cells. We investigated the differentially expressed lncRNAs in different oxygen concentrations using next-generation sequencing (NGS) and validated these results through quantitative reverse transcription polymerase chain reaction (qRT-PCR). We found an lncRNA, NDRG1-OT1, that was up-regulated during hypoxia and down-regulated during reoxygenation. Next, we identified the differentially expressed genes regulated by NDRG1-OT1 using microarrays and confirmed these results through qRT-PCR and Western blotting. We found an oxygen responsive gene, NDRG1, was inhibited by NDRG1-OT1. Furthermore, Ingenuity Pathway Analysis(IPA) indicated that NDRG1-OT1 could involve in the Ubiquitin-proteasome pathway. We considered NDRG1-OT1 might regulate NDRG1 stability and ubiquitination, and we are proving these possibility by immunoblotting and immunoprecipitation. These findings may provide new insights into epigenetic regulation of breast cancer during hypoxia.
Citation Format: Hsin-Chen Lin, Liang-Chuan Lai, Hsing-Guang Chen, Hung-Hsin Chen, Mei-Hung Chang, Mong-Hsun Tsai, Eric Y. Chung. Hypoxic long noncoding RNA NDRG1-OT1 inhibit NDRG1 in MCF-7 breast cancer cell line. [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 975.
Abstract 98: The somatic mutational landscape of the mitochondrial genome in prostate cancer: evaluation of clinical impact
Authors: Hopkins Julia F. , Sabelnykova Veronica Y. , Watson John , Heisler Lawrence E. , Zhang Junyan , Fraser Michael , van der Kwast Theodorus , Bristow Robert G. , Boutros Paul C. 
Published: July 2016

Abstract
Prostate cancer remains the most prevalent and second most lethal non-skin cancer in men. Whole genome studies have provided important insights into specific driver genes, however most of these studies have not assessed one key portion of the genome: the mitochondrial genome. To gain a complete understanding of the most commonly-diagnosed sub-groups of prostate cancer: low- and intermediate-risk localized disease, we surveyed the mitochondrial genomes from next-generation sequencing (NGS) data of over 300 tumour samples from prostate cancer patients. These samples were mainly from prostate cancer patients with clinical Gleason Scores of 3+3, 3+4 and 4+3. All had at least 5 years of follow-up data (median &gt; 8 years), allowing identification of clinical associations with identified somatic mutations via Cox Proportional Hazards modeling and machine-learning. Recurrent somatic mutations in mtDNA were identified, and these were associated with clinical outcomes. One third of patients were found to have a somatic mtDNA mutation. These mutations appear to be associated with age of patient. The mtDNA region with the majority of mutations was the regulatory D-loop region, although certain proteins had high numbers of mutations. Those somatic mutations occurring within the coding regions in general were nonsynonymous. Specific identified candidate somatic mutations were validated via Sanger sequencing. Clinical associations between somatic were also integrated with existing copy-number alteration (CNA) biomarkers using machine learning methods to evaluate performance. mtDNA mutations were also compared to identified aberrations (CNA, PGA, SNVs) within the nuclear genome to determine correlations between the two genomes, in addition to other somatic mutations or altered-expression in nuclear-encoded mitochondrial proteins. Taken together, these data demonstrate a key role for mitochondrial mutations in driving prostate cancer.
Citation Format: Julia F. Hopkins, Veronica Y. Sabelnykova, John Watson, Lawrence E. Heisler, Junyan Zhang, Michael Fraser, Theodorus van der Kwast, Robert G. Bristow, Paul C. Boutros. The somatic mutational landscape of the mitochondrial genome in prostate cancer: evaluation of clinical impact. [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 98.
Abstract 984: LncRNA LINC00668 predicts a poor prognosis of gastric cancer and promotes cell proliferation through epigenetically silencing of CKIs
Authors: Chen Jinfei 
Published: July 2016

Abstract
Recently, long noncoding RNAs (lncRNAs) have been shown to have important regulatory roles in human cancer biology. By utilizing publicly available lncRNAs expression profiling data of gastric cancer and integrating analyses, we screened out LINC00668, whose expression is significantly increased and is correlated with outcomes in gastric cancer (GC). Further experiments revealed that LINC00668 knockdown significantly repressed the proliferation both in vitro and in vivo. Mechanistic investigations showed that LINC00668 was a direct transcriptional target of E2F transcription factor 1 (E2F1). Moreover, we also found that LINC00668 plays a key role in G0/G1 arrest, and further demonstrated that LINC00668 was associated with PRC2 and that this association was required for the epigenetic repression of cyclin-dependent protein kinase inhibitors (CKIs), including p15, p16, p21, p27 and p57, thus contributing to the regulation of gastric cancer cell cycle. To our knowledge, this is the first report showed that the role and molecular mechanism of LINC00668 in cancer. Together, our results suggest that E2F1-regulated LINC00668, as a cell cycle regulator, enriches a mechanistic link between lncRNA and E2F1-mediated cell cycle regulation pathway and may serve as a candidate prognostic biomarker and target for new therapies in human gastric cancer.
Key words: E2F1; LINC00668; cell cycle; proliferation; gastric cancer
Acknowledgements: The work was partly supported by the National 973 Basic Research Program of China (Grant No. 2013CB911300) grants from the National Natural Science Foundation of China (Grant No. 81272469, 81502071 and 81572928) and the clinical special project for Natural Science Foundation of Jiangsu Province (Grant No. BL2012016), and the grant from Nanjing 12th Five-Year key Scientific Project of medicine to Dr. Jinfei Chen.
Citation Format: Jinfei Chen. LncRNA LINC00668 predicts a poor prognosis of gastric cancer and promotes cell proliferation through epigenetically silencing of CKIs. [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 984.
Abstract 985: Downregulation of long noncoding RNA TINCR promotes invasion and metastasis and predicts poor prognosis in tongue squamous cell carcinoma
Authors: Zhuang Zehang , Wang Cheng , Xie Nan , Wu Yue , Hou Jinsong , Liu Xiqiang , Huang Hongzhang 
Published: July 2016

Abstract
Background and aim: Recently long non-coding RNAs (lncRNAs) have emerged as new gene regulators involving in a number of developmental and tumorigenic processes. However, few lncRNAs have been well characterized in tongue squamous cell carcinoma (TSCC). The aim of this study is to determine whether lncRNAs play a role in TSCC progression.
Methods: The expression profiles of lncRNAs and protein-coding genes in TSCC tissues and paired adjacent non-tumor tissues from 10 patients were compared by using lncRNA microarrays. TSCC-specific gene co-expression networks were constructed by differential expression analysis and weighted gene co-expression network analysis (WGCNA). Levels of these differentially expressed lncRNAs were verified in TSCC tissues (n = 45) using Quantitative real-time PCR (qRT-PCR) and further confirmed in another patient cohort (n = 103) by in situ hybridization (ISH). The effects of lncRNA on tumor cell invasion and migration were assessed by silencing or overexpressing the lncRNA in vitro.
Results: A total of 815 lncRNAs and 1783 protein-coding genes were differentially expressed between TSCC tissues and paired adjacent non-tumor tissues. WGCNA showed that one of the co-expression networks was significantly enriched for biological process that was relevant to epithelial cell differentiation, among which, TINCR was significantly down-regulated. Both PCR and ISH analyses validated that the down-regulation of TINCR in tumor tissues compared with controls. The expression level of TINCR was associated with tumor size, differentiation, cervical lymph node metastasis status, clinical stage and outcomes in patients with TSCC.Patients with TINCR low expression had a reduced overall survival. COX regression analysis showed that TINCR can be served as an independent prognostic factor for patients with TSCC. More, ectopic transfection of TINCR dramatically suppressed cell invasion and migration in vitro. On the contrary, knockdown of TINCR led to p63 upregulation, and enhanced cell invasion and migration.
Conclusion: Our study suggests that downregulation of TINCR plays a role in TSCC progression, at least partially, by regulating epithelial differentiation-associated genes.
Citation Format: Zehang Zhuang, Cheng Wang, Nan Xie, Yue Wu, Jinsong Hou, Xiqiang Liu, Hongzhang Huang. Downregulation of long noncoding RNA TINCR promotes invasion and metastasis and predicts poor prognosis in tongue squamous cell 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 985.
Abstract 987: A novel cell cycle-associated lncRNA, HOXA11-AS, is transcribed from 5-prime end of HOXA transcript and a biomarker of progression in glioma
Authors: Wang Qixue , Zhang Junxia , Liu Yanwei , Zhou Junhju , Kang Chunsheng , Han Lei 
Published: July 2016

Abstract
The comprehensive lncRNA expression signature in glioma remains fully unknown. We performed a high throughput microarray to detect ncRNA expression profile in 225 human glioma tissues. One novel lncRNA, HOXA11-AS with unknown function, is the antisense transcript of HOX11 gene. The results showed that HOXA11-AS was closely associated with glioma grade and poor prognosis. Multivariate cox regression analysis revealed that HOXA11-AS was an independent prognostic factor in glioblastoma multiforme patients and its expression was correlated with glioma molecular subtype of the Cancer Genome Atlas. Gene set enrichment analysis indicated that gene sets most correlated with HOXA11-AS expression involved in cell cycle progression. Overexpression of HOXA11-AS transcript promoted cell proliferation in vitro while knockdown of HOXA11-AS expression manifested a repressive function during these cellular processes via regulating cell cycle progress. The growth promoting and inhibiting effect of HOXA11-AS was also demonstrated in a xenograft mouse model. For the first time, our data confirms that HOXA11-AS is an important long non-coding RNA that primarily serves as a prognostic factor for glioma patient survival, a biomarker for identifying glioma molecular subtypes, and therapeutic target for glioma patient.
Citation Format: Qixue Wang, Junxia Zhang, Yanwei Liu, Junhju Zhou, Chunsheng Kang, Lei Han. A novel cell cycle-associated lncRNA, HOXA11-AS, is transcribed from 5-prime end of HOXA transcript and a biomarker of progression in glioma. [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 987.
Abstract 999: P16 DNA methylation inactivates transcription of IncRNA ANRIL
Authors: Gan Ying , Zhang Baozhen , Cui Chenghua , Deng Dajun 
Published: July 2016

Abstract
The exonic ANRIL (P15AS) is a 3.8-kb lncRNA transcribed from the antisense strand of the P14 promoter and flanking regions. Recently, we have constructed a P16 promoter DNA methyltransferase (P16-Dnmt) using the pTRIPZ vector that can specifically methylate human P16 CpG islands and found that P16 methylation directly leads to gene transcription silence [Cui et al. Genome Biology 2015, 16:252]. However, whether ANRIL transcription is affected by P16 DNA methylation has not previously been reported. In the present study, correlation between endogenous P16, P15, P14 mRNA and ANRIL levels in a panel of cell lines were determined using quantitative RT-PCR. Unexpectedly, the results showed that ANRIL transcriptional level was positively and significantly correlated with the P16 mRNA level (r = 0.774, P = 0.003), but not correlated with the P15 or P14 mRNA levels (r = 0.09 or 0.30, P = 0.78 or 0.35). These phenomena were confirmed using the public available transcriptome data in the Broad-Novartis Cancer Cell Line Encyclopedia (CCLE). Furthermore, transcription of both ANRIL and P16 mRNA were observed only in cancer cell lines in which the P16 alleles are unmethylated (Caski, SGC7901, BGC823, GES1, Siha and HeLa), but not in these cell lines in which the P16 alleles are fully methylated (Colo205, PC3, MHCC97H, RKO, SW480 and AGS). These suggest the possibility that methylation of the P16 promoter may inactivate transcription of ANRIL as well as P16. To study the possible causality between P16 DNA methylation and transcriptional silence of ANRIL, we employed P16-Dnmt to induce P16-specific DNA methylation in gastric cancer BGC823 cells, and found that transcription levels of both P16 and ANRIL were significantly decreased by the induced P16 DNA methylation (P&lt;0.001 and 0.024, respectively). Besides, transcription level of P14 was also reduced (P = 0.043) while the P14 promoter CpG islands remained to be unmethylated. In contrast, P16 DNA demethylation induced by an artificial P16-specific transcription factor [Zhang et al. Human Gene Therapy 2012, 23:1071-81] re-activated transcription of both ANRIL and P16 in H1299 cells (P&lt;0.001). The mechanism of inactivation of ANRIL expression by P16 DNA methylation is under investigation. In conclusion, transcription of ANRIL is regulated by P16 DNA methylation.
Citation Format: Ying Gan, Baozhen Zhang, Chenghua Cui, Dajun Deng. P16 DNA methylation inactivates transcription of IncRNA ANRIL. [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 999.