bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A27: Long noncoding RNA expression in cytogenetically normal acute myeloid leukemia identifies a distinct signature associated with NPM1 mutations
Authors: Clara Etienne De , Ma Hanjing , Vergez François , Quelen Cathy , Dejean Sébastien , Demur Cécile , Delabesse Eric , Recher Christian , Touriol Christian , Martelli Maria Paola , Falini Brunangelo , Brousset Pierre , Bousquet Marina 
Published: May 2016

Abstract
Long noncoding RNAs (lncRNAs) are defined as RNA transcripts that are larger than 200 nt but do not appear to have protein-coding potential. Cumulative evidence points towards an important role of lncRNAs in cancer initiation, development, and progression. In this study we sought to evaluate the lncRNA expression profile of patients with cytogenetically normal acute myeloid leukemia (CN-AML). RNA sequencing of forty CN-AML patients allowed us to identify more than 8000 previously-undescribed lncRNAs. Using unsupervised analysis we observed a specific lncRNA signature dependent on the mutational status of the nucleophosmin (NPM1) gene. Sparse partial least squares discriminant analysis allowed us to identify a minimal set of 19 lncRNAs capable of discriminating NPM1-mutated from NPM1-wild type patients. Among these, we found that expression of the XLOC_087120 lncRNA inversely correlates with its neighboring histone-coding genes. XLOC_087120 also interacts with SUZ12, a component of the Polycomb Repressive Complex 2, suggesting a role for this lncRNA in the epigenetic repression of histone genes and therefore a potential impact on chromatin remodeling. Indeed, its overexpression in cell lines leads to a downregulation of histone genes. Furthermore, we demonstrated that mutant NPM1 modulates the nuclear/cytoplasmic localization of XLOC_087120. Altogether, these data suggest that lncRNAs should be considered as key players in the pathogenesis of acute myeloid leukemias.
Citation Format: Etienne De Clara, Hanjing Ma, François Vergez, Cathy Quelen, Sébastien Dejean, Cécile Demur, Eric Delabesse, Christian Recher, Christian Touriol, Maria Paola Martelli, Brunangelo Falini, Pierre Brousset, Marina Bousquet. Long noncoding RNA expression in cytogenetically normal acute myeloid leukemia identifies a distinct signature associated with NPM1 mutations. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr A27.
Abstract A36: A systematic network-based approach to prioritizing lncRNA drivers in cancers
Authors: Li Jun , Zhou Zhicheng , Liang Han 
Published: May 2016

Abstract
Introduction: Decades of efforts have been made to have a better understanding about the human genome, which encodes ~20,000 protein-coding genes as well as an astounding number of transcriptionally active noncoding RNAs. Among these noncoding RNAs, long-noncoding RNAs (lncRNAs) have been increasingly recognized to play essential roles in tumorigenesis, representing a new focus in cancer research. Analogous to the identification of protein-coding cancer driver genes, it is a crucial task in cancer research to identify lncRNA drivers and elucidate their functions in various cancer types.
Methods: We first downloaded TCGA RNA-seq BAM files (&gt;60TB) across 20 cancer types from the UCSC Cancer Genomic Hub (CGHub) and quantified the lncRNA expression based on GENCODE lncRNA annotation. To identify lncRNA drivers, we focused on identifying the functional relevant lncRNA-protein pairs through their expression profiling data. To prevent acquiring more false positives from conventional correlation analysis, we applied the context likelihood of relatedness (CLR) algorithm on evaluating co-expressed lncRNA and protein pairs based on RNA-seq and reverse-phase protein array (RPPA) data. In addition, to further increase the clinical relevance of the potential lncRNA drivers, we conducted survival analysis and tumor/normal differential analysis to boost the prediction power of our systematic computational approach.
Results: In this study, we integrated lncRNA expression, protein expression and patient survival data to nominate lncRNA drivers in 20 cancers. Among ~4 million lncRNA-protein pairs, we have identified 9 lncRNA drivers and 16 potential lncRNA-protein interaction pairs linked with them. To validate our findings, we selected 3 lncRNAs with high confidence and performed knockdown experiments in multiple cell lines, in which 2 lncRNAs (TMPO-AS1 and HCP5) showed functional relevance with protein-coding genes MSH6 and LCK respectively. Both of the pairs have the same direction of correlations (positive or negative) as we predicted. Our results indicate that the identified lncRNAs may functionally interact with their protein partners identified by our network-based approach, which will further provide the molecular foundation for investigating cancer mechanisms, identifying prognostic lncRNA markers and characterizing additional therapeutic targets.
Citation Format: Jun Li, Zhicheng Zhou, Han Liang. A systematic network-based approach to prioritizing lncRNA drivers in cancers. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr A36.
Abstract A43: Long noncoding RNAs as targets of mammary tumor cell proliferation and migration
Authors: Diermeier Sarah D. , Chang Kung-Chi , Freier Susan M. , Rigo Frank , Bennett C. Frank , Spector David L. 
Published: May 2016

Abstract
Objective: Recent genome-wide studies revealed that as much as 80% of the human genome can be transcribed whereas only 2% of this RNA is translated into proteins. Non-coding transcripts can be subdivided into several groups, with long non-coding RNAs (lncRNAs) representing the largest and most diverse class. With breast cancer being the most frequent malignancy in women worldwide, we set out to investigate the potential of lncRNAs as novel therapeutic targets.
Methods: We focused on the luminal B and the HER2/neu-positive subtypes of breast cancer, as both are associated with high prevalence and bad prognosis. By performing RNA-Seq on tumor sections and mammary organoids from MMTV-PyMT and MMTV-Neu-NDL mice, modeling the luminal B and HER2/neu-amplified subtypes of human breast cancer respectively, we generated a comprehensive catalog of differentially expressed lncRNAs. We functionally validated the role of a subset of these lncRNAs by antisense oligonucleotide (ASO) mediated knockdown in primary mammary tumor cells and 3D ex vivo organoids.
Results: We identified several hundred potentially oncogenic lncRNAs that were over-expressed in a subtype-specific manner as well as numerous lncRNAs up-regulated in both MMTV-PyMT and MMTV-Neu-NDL tumors. To narrow down the candidate list of lncRNAs with the highest therapeutic potential, we sorted the data computationally and defined a subset of previously uncharacterized lncRNAs as Mammary Tumor Associated RNAs (MaTARs). Upon independent knockdown of several MaTARs, we observed significantly reduced cell proliferation, invasion and/or collective cell migration in a cancer-specific context.
Conclusion: MaTARs are likely important drivers of mammary tumor progression and/or metastasis and represent promising new therapeutic targets. Future studies will focus on the molecular characterization of these lncRNAs and elucidation of their potential role(s) in mammary tumor progression and metastasis.
Citation Format: Sarah D. Diermeier, Kung-Chi Chang, Susan M. Freier, Frank Rigo, C. Frank Bennett, David L. Spector. Long noncoding RNAs as targets of mammary tumor cell proliferation and migration. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr A43.
Abstract B07: Long noncoding RNAs underlying genetic predispositions to prostate cancer
Authors: Guo Haiyang , Ahmed Musaddeque , Hua Junjie Tony , Liang Yi , He Housheng Hansen 
Published: May 2016

Abstract
Trait-associated SNPs identified through Genome-Wide Association Studies are enriched in regulatory regions. However, the functional link between these SNPs and their target genes remains elusive. Due to their involvement in fundamental biological processes, long noncoding RNAs (lncRNAs) represent an attractive class of molecules mediating cancer risk. Through integrative analysis of the lncRNA transcriptome with genomic and prostate cancer risk SNP data, we identified 60 candidate lncRNAs associated with risk to prostate cancer. The mechanism underlying the top hit, PCAT1, was evaluated further. The risk variant at rs7463708 decreases HOXB13 and increases AR binding at a distal enhancer that loops to PCAT1 promoter, resulting in upregulation of PCAT1 upon prolonged androgen treatment. In addition, PCAT1 interacts with AR and LSD1 and is required for their recruitment to the enhancers of GNMT and DHCR24, two androgen late response genes implicated in prostate cancer development and progression. These findings suggest that modulating lncRNA expression is an important mechanism for risk SNPs in promoting prostate transformation.
Note: This abstract was not presented at the conference.
Citation Format: Haiyang Guo, Musaddeque Ahmed, Junjie Tony Hua, Yi Liang, Housheng Hansen He. Long noncoding RNAs underlying genetic predispositions to prostate cancer. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr B07.
Abstract B13: Eradication of neuroblastoma by suppressing the expression of a single long noncoding RNA
Authors: Liu Pei Y. , Tee Andrew E. , Atmadibrata Bernard , Mestdagh Pieter , Vandesompele Jo , Dinger Marcel , Liu Tao 
Published: May 2016

Abstract
Neuroblastoma is the most common solid tumour in early childhood, and accounts for approximately 15% of all childhood cancer death. N-Myc gene amplification occurs in one quarter to one third of human neuroblastoma tissues, and the majority of patient with neuroblastoma due to N-Myc gene amplification die of the disease. We performed RNA sequencing experiments, and identified 5 transcripts, including RP1X, which were considerably differentially expressed between N-Myc gene amplified and non-amplified human neuroblastoma cell lines. Affymetrix microarray studies revealed that DEPDC was one of the few genes considerably down-regulated in neuroblastoma cells after RP1X depletion. Chromatin immunoprecipitation assays showed that knocking-down RP1X expression reduced histone H3 lysine 4 trimethylation, a marker for active gene transcription, at the DEPDC gene promoter. Depletion of RP1X or DEPDC significantly reduced ERK protein phosphorylation, N-Myc protein phosphorylation at Serine 62, N-Myc protein stabilization, neuroblastoma cell proliferation and survival. Clonogenic assays showed that knocking-down RP1X with doxycycline completely abolished colony formation capacity of neuroblastoma cells stably transfected with doxycycline-inducible RP1X shRNA. Importantly, treatment with doxycycline in mice xenografted with neuroblastoma cells stably transfected with doxycycline-inducible RP1X shRNA, led to tumour eradication. In human neuroblastoma tissues from 600 neuroblastoma patients, high levels of RP1X gene expression correlated with DEPDC gene expression and poor patient prognosis. In conclusion, this study identifies the novel long noncoding RNA RP1X as an important regulator of N-Myc protein stability and neuroblastoma tumourigenesis.
Citation Format: Pei Y. Liu, Andrew E. Tee, Bernard Atmadibrata, Pieter Mestdagh, Jo Vandesompele, Marcel Dinger, Tao Liu. Eradication of neuroblastoma by suppressing the expression of a single long noncoding RNA. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr B13.
Abstract B23: Role of noncoding RNAs in regulating human papilloma virus-16 (HPV-16) induced oncogenesis in head and neck squamous cell carcinoma (HNSCC)
Authors: Sannigrahi Malay Kumar , Singh Varinder , Sharma Rajni , Panda Naresh K. , Khullar Madhu 
Published: May 2016

Abstract
Background: HPV is an emerging risk factor for HNSCC, however, molecular mechanisms in HPV mediated HNSCC remains poorly delineated. Recent studies suggest that non-coding RNAs may play an important role in the aetiology of HNSCC. In the present study, we examined microRNAs involved in HPV-16 induced HNSCC.
Material and Method: Tissue samples from HNSCC patients (n=300) were screened for HPV-16 using PCR based approach with consensus PCR primers (MY09/MY11, Gp5+/Gp6+), HPV16-specific PCR, HPV-16 E7 mRNA, immunohistochemistry (p16, p53 and pRB) and viral-load determination. In-silico approach was used to identify host miRNAs with HPV-16 mRNAs as putative target. Differential expression of identified miRNAs was determined by qRT-PCR in HPV-16 positive (UPCI:SCC090, CaSki, SiHa), HPV negative (UPCI:SCC116, HaCat) and transfected with HPV 16 full genome plasmid cell lines, and, HPV 16-positive/HPV-negative tissue samples. Putative targets of identified miRNAs were identified by bioinformatic approach and their mRNA levels were determined by qRT-PCR in HPV positive and negative cell lines, and tissue samples. Over-expression and inhibition studies with miRNA mimic and inhibitor were done to identify affected viral and host oncogenic pathways.
Results: Total 32 HNSCC patients were found to be HPV-16 positive. We identified 10 miRNAs with HPV-16 as putative target. Among them hsa-miR-139-3p showed significant down-regulation in HPV-16 positive samples and cell lines compared to HPV negative controls. Using bioinformatics tools, hsa-miR-139-3p was found to target viral HPV-16 E1 and host HOXB6 gene. Transfection with hsa-miR-139-3p mimic resulted in significant down-regulation of HPV 16 early mRNA as well as its targeted genes in luciferase-3'UTR assay. Moreover, mimic transfected HPV-positive cell lines showed dysregulated MEK-ERK signaling pathway.
Conclusion: Our results suggest hsa-miR-139-3p may be involved in patho-physiology of HPV-16 positive HNSCC as it deregulates expression of HPV oncogenic proteins and cell proliferation by targeting MEK-ERK signaling pathway.
Citation Format: Malay Kumar Sannigrahi, Varinder Singh, Rajni Sharma, Naresh K. Panda, Madhu Khullar. Role of noncoding RNAs in regulating human papilloma virus-16 (HPV-16) induced oncogenesis in head and neck squamous cell carcinoma (HNSCC). [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr B23.
Abstract B26: OIP5-Antisense 1, a long noncoding RNA deregulated in non-small cell lung cancer
Authors: Stewart Greg L. , Enfield Katey SS , Rowbotham David A. , Hubaux Roland , Martinez Victor , Lam Stephen , Lam Wan 
Published: May 2016

Abstract
Background: Lung cancer represents an enormous health burden, representing the most common cause of cancer death worldwide. The poor therapeutic outcome is largely due to a complex molecular background as well as late stage diagnosis, with most patients presenting unresectable local tumors, or metastatic disease. While mutations of driver genes is a well-known mechanism, approximately half of all non-small cell lung cancer (NSCLC) tumors harbor no known clinically relevant oncogenic drivers, emphasizing the need to explore alternative mechanisms such as non-coding RNAs (ncRNAs). Natural antisense transcripts (NATS) are ncRNAs that are expressed from the opposite strand of coding mRNAs. These genes overlap with, and are often involved in the regulation of their sense counterparts. NATs can recruit regulatory complexes to their transcriptional locus, leading to silencing of transcription and have recently been described in cancer to silence tumor suppressor genes. NATs are quite prevalent as it is estimated that 25-40% of genes display overlapping transcription, however only a few NATs have been characterized, emphasizing the need to explore these ncRNAs in the context of NSCLC.
Hypothesis: We hypothesize NATs of NSCLC-related genes are deregulated in NSCLC.
Methods: We performed RNAseq and miRNAseq on a set of 65 NSCLC tumors including 36 adenocarcinomas and 29 squamous cell carcinomas as well as matched non-malignant lung tissue. A sign rank test was used to identify NATs with significantly altered expression between tumor and matched normal. Survival analysis was done using a Cox Proportional hazard model, as well as the Kaplan-Meier method.
Results: We have identified a NAT of OIP5, a lung cancer oncogene required for chromatin segregation, to be significantly underexpressed, while its sense counterpart, OIP5 mRNA, is significantly overexpressed. We also find that expression of both OIP5 and OIP5-AS1 has a significant impact on 5 year survival. These findings suggest that deregulation of OIP5 through its antisense RNA may represent a novel mechanism regulating tumor phenotypes in NSCLC.
Citation Format: Greg L. Stewart, Katey SS Enfield, David A. Rowbotham, Roland Hubaux, Victor Martinez, Stephen Lam, Wan Lam. OIP5-Antisense 1, a long noncoding RNA deregulated in non-small cell lung cancer. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr B26.
Abstract B39: Long noncoding RNA PCAT14/PRCAT104; A prognostic biomarker in prostate cancer
Authors: Malik Rohit , Zhang Xiang , Shukla Sudhanshu , Niknafs Yashar Y. , Zhao Shuang , Feng Felix Y. , Chinnaiyan Arul M. 
Published: May 2016

Abstract
Prostate cancer is the second most common epithelial cancer and the second leading cause of cancer-related death for men in the United States. While majority of prostate cancer cases are indolent and cause minimal morbidity and mortality, a subset of men progress to a hormone-refractory aggressive disease with high mortality. Markers such as PSA and PCA3 perform well in diagnosis of disease; however these biomarkers are unable to predict disease progression. Therefore, there is an urgent need to identify clinical predictors of disease progression. Long non-coding RNAs (lncRNAs) are emerging as an important class of biomolecules that exhibit significant lineage- and cancer-specificity making them ideal biomarker candidates.
Using RNA-Seq data from The Cancer Genome Atlas (TCGA) and as well as from libraries generated in our laboratory, we identified PCAT14/PRCAT104 as a marker of low Gleason disease. PCAT14 was shown to be highly expressed in prostate cancer compared to benign tissue; however, its expression in prostate cancer was limited to low Gleason disease. To directly evaluate the relationship between PCAT14 levels and clinical outcome, we assessed its expression in more that 1600 Prostate cancer samples by a high-density Affymetrix GeneChip platform. In all 5 cohorts analyzed, PCAT14 was shown to be a strong prognostic marker in its ability to predict biochemical recurrence, clinical progression to systemic disease and prostate cancer–specific mortality. Furthermore, in a multivariate analysis, PCAT14 expression also predict resistance to androgen deprivation therapy (ADT) (p=0.012). More interestingly, PCAT14 was able to add to prognostic value of SCHLAP1, a lncRNA that we previously showed to be an excellent prognostic marker in prostate cancer. PCAT14 in combination with SCHLAP1 was able better in predicting 10-year metastasis free survival (AUC: 0.64) than SCHLAP1 alone (AUC=0.58). Taken together, we identified a novel marker of low grade prostate cancer that in combination with SCHALP1, a marker of aggressive cancer, can predict disease progression and hence can be of immense value for treatment individualization in prostate cancer
Citation Format: Rohit Malik, Xiang Zhang, Sudhanshu Shukla, Yashar Y. Niknafs, Shuang Zhao, Felix Y. Feng, Arul M. Chinnaiyan. Long noncoding RNA PCAT14/PRCAT104; A prognostic biomarker in prostate cancer. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr B39.
Abstract IA06: Disregulation of lncRNAs helps drive Ewing sarcoma pathogenesis
Authors: Sweet-Cordero Alejandro 
Published: May 2016

Abstract
Pediatric sarcomas are orphan diseases that cause significant morbidity and mortality in children, adolescents and young adults. Among the most intriguing pediatric sarcomas is Ewing sarcoma. The (11;22)(q24;q12) translocation, which leads to expression of EWS/FLI, is identified in 85% of Ewing sarcoma cases. Ewing sarcoma cells carrying this translocation have a strict dependency on its expression, suggesting that the translocation is a critical oncogenic event in this disease. Despite intensive investigation, the mechanisms through which EWS/FLI leads to oncogenesis are incompletely understood. Recent data indicates that two distinct mechanisms are involved. In one, EWS/FLI leads to gene activation by acting as a pioneer transcription factor at novel enhancers. In another, EWS/FLI forces the removal of ets binding factors from their established binding sites and acts as a transcriptional repressor. How these two diverse functions are orchestrated at a molecular level remains unclear.
Given the widespread transcription of long non-coding RNAs and their emerging role in gene regulation, they are strong candidates for participation in the complex genetic rewiring program induced by EWS/FLI. We recently described the first lncRNA clearly regulated by EWS/FLI, (EWS-associated transcript 1, EWSAT1). Expression of EWS/FLI drives upregulation of EWSAT1 most likely by direct transcriptional regulation. EWSAT1 in turn plays a critical role in EWS/FLI-mediated gene repression, at least in part by interacting with the RNA binding protein hnRNPK. RNAseq analysis indicates that EWS/FLI regulates the expression of a large number of other lncRNAs in addition to EWSAT1. We have identified lnc659 (EWSAT2) as a second Ewing sarcoma-related transcript with functional relevance to Ewing pathogenesis. EWSAT2 is upregulated by expression of EWS/FLI and knock-down of EWSAT2 strongly decreases the proliferation of Ewing sarcoma cell lines in vitro and the oncogenicity of cell lines and patient-derived xenografts in vivo. Ongoing studies are directed at identifying the molecular mechanism of action of EWSAT1 and EWSAT2 as well as other lncRNAs in the pathogenesis of Ewing sarcoma.
Citation Format: Alejandro Sweet-Cordero. Disregulation of lncRNAs helps drive Ewing sarcoma pathogenesis. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr IA06.