bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A44: Randomized adapter pools for microRNA sequencing of colorectal cancer cell lines and primary tumors
Authors: Eide Peter W. , Cekaite Lina , Xu Ping , Meza-Zepeda Leonardo A. , Dalmay Tamas , Lothe Ragnhild A. 
Published: May 2016

Abstract
Single-nucleotide resolution, high throughput and excellent precision make small RNA sequencing ideally suited for addressing a wide array of microRNA (miRNA) research questions. It is however known that adapter ligation introduces bias distorting the relation between sample expression levels and sequencing read counts. To investigate how this issue may affect studies aiming to identify miRNA biomarkers, we utilized the recently published High Definition library preparation protocol to generate miRNA profiles of 35 colorectal cancer cell lines, 55 primary cancer biopsies and 5 adjacent normal mucosa samples. The protocol minimizes ligation bias by means of randomized adapter pools. Comparing the resulting data against publicly available colorectal cancer miRNA datasets, we demonstrate that the High Definition protocol moderates read count distributions, increases accuracy and improves sensitivity while maintaining high reproducibility. Moreover, by taking advantage of the more quantitative read counts, the cancer cell line panel and the normal mucosa samples, we identify a set of miRNAs that are highly expressed in epithelial cancerous cells, deregulated in colorectal cancer as compared to normal mucosa and differentially expressed between established molecular subgroups. As such, these miRNAs present strong candidates for functional validation and biomarker testing. In conclusion, we here present High Definition miRNA sequencing data for a large panel of clinically relevant colorectal cancer samples highlighting the potential of improved small RNA library preparation methods.
Citation Format: Peter W. Eide, Lina Cekaite, Ping Xu, Leonardo A. Meza-Zepeda, Tamas Dalmay, Ragnhild A. Lothe. Randomized adapter pools for microRNA sequencing of colorectal cancer cell lines and primary tumors. [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 A44.
Abstract A45: GAS5-encoded intronic snoRNAs produce specific sdRNAs overexpressed in aggressive prostate cancer
Authors: Martens-Uzunova Elena S. , Kalsbeek Anton , Hoogstrate Youri , Baker Adam , Nielsen Soren Jensby , Visakorpi Tapio , Bangma Chris , Jenster Guido 
Published: May 2016

Abstract
Small non-coding RNAs, such as miRNAs, are implicated in carcinogenesis. To investigate changes in the entire small RNA transcriptome in prostate cancer (PCa) we analyzed 11 clinical sample pools representing different stages of PCa by deep sequencing. We found that most C/D-box small nucleolar RNAs (snoRNAs) are specifically processed to smaller snoRNA-derived RNAs (sdRNAs) highly expressed in PCa. In particular, SNORD78 produces sdRNAs strongly up-regulated in PCa. Together with 9 other snoRNAs, SNORD78 is encoded in the introns of the Growth Arrest Specific 5 gene (GAS5).
Examination of SNORD78 and the positioned in a neighboring intron SNORD44 showed that both snoRNAs produce predominantly one sdRNA fragment each, specifically originating from the 3'-arm (SNORD78) or the 5'-arm (SNORD44) of the precursor sequence. Inspection of the secondary structures of SNORD44 and SNORD78 revealed that they have a degenerated C'/D' box and can fold in a tight hairpin similarly to miRNAs. In contrast, SNORD74 and SNORD81 that also encoded in introns of GAS5, contain canonical C'/D' boxes and each produce three equally expressed sdRNAs.
Quantitative real time PCR analysis in an independent patient cohort of 106 fresh-frozen clinical samples confirmed the significant up-regulation of all four snoRNAs and their derivative sdRNAs in PCa samples compared to normal tissue. Interestingly, the increased expression of snoRNAs and sdRNAs was not associated with elevated levels of GAS5 transcript.
Based on these results, we conclude that (i) separate regulatory mechanisms control the posttranscriptional processing of the spliced GAS5 transcript and the encoded in its introns snoRNAs; (ii) SNORD44, SNORD78, SNORD74 and SNORD81 function as precursors of different sdRNAs; (iii) SNORD44, SNORD78, SNORD74 and SNORD81 and their derivative sdRNAs are significantly up-regulated in PCa and carry biomarker potential for this disease.
Citation Format: Elena S. Martens-Uzunova, Anton Kalsbeek, Youri Hoogstrate, Adam Baker, Soren Jensby Nielsen, Tapio Visakorpi, Chris Bangma, Guido Jenster. GAS5-encoded intronic snoRNAs produce specific sdRNAs overexpressed in aggressive 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 A45.
Abstract B05: MicroRNA-206 drives rhabdomyosarcoma differentiation through downregulation of PAX7
Authors: Hanna Jason A. , Garcia Matthew R. , Go Jonathan C. , Finkelstein David , Kodali Kiran , Pagala Vishwajeeth , Olson Eric N. , Peng Junmin , Hatley Mark E. 
Published: May 2016

Abstract
The goal of this work is to understand the mechanism of microRNA-206 (miR-206) induced differentiation in rhabdomyosarcoma (RMS). RMS is the most common soft tissue sarcoma of childhood with both histology and gene expression suggestive that RMS tumor cells resemble a developmental arrest of skeletal muscle. miR-206 is a skeletal muscle specific miRNA expression increases through normal muscle development and has decreased levels in RMS compared to normal skeletal muscle. Exogneous miR-206 replacement drives differentiation and cell cycle exit of RMS. However, the target genes responsible for the relief of the development arrest are largely unknown. Using a combinatorial approach with mRNA microarrays and tandem mass tag (TMT) proteome profiling we identified 165 mRNAs and 272 proteins downregulated in miR-206 mimic transfected RMS cells. Potential targets were validated with 3'UTR reporter assays as well as real-time PCR and immunoblot from miR-206 mimic transfected cells. Further analysis with genetic rescue identified the key targets responsible for the RMS differentiation block as PAX7, PAX3, CCND2, and NOTCH3. However, siRNA knockdown of these targets alone and in a pooled combination failed to induce differentiation to the same extent as miR-206 despite knockdown levels comparable to miR-206. Thus, target identification collectively is key to understanding the mechanism of miR-206 function in RMS, suggesting the one miRNA-one target model to be insufficient for the complex phenotype of miR-206 induced differentiation. Genetic deletion of miR-206 in a mouse model of RMS accelerated and exacerbated tumor development indicating that both in vitro and in vivo miR-206 possesses tumor suppressive properties. In addition, Notch3 and Pax7 levels were increased in knockout tumors compared to wild type, providing further evidence for these genes as key targets of miR-206 in RMS. These results illustrate that miR-206 relieves the differentiation arrest in RMS and suggests that miR-206 replacement therapy could be a potential therapeutic strategy.
Citation Format: Jason A. Hanna, Matthew R. Garcia, Jonathan C. Go, David Finkelstein, Kiran Kodali, Vishwajeeth Pagala, Eric N. Olson, Junmin Peng, Mark E. Hatley. MicroRNA-206 drives rhabdomyosarcoma differentiation through downregulation of PAX7. [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 B05.
Abstract B10: Overexpression of the lncRNA PVT1 contributes to the cervical cancer phenotype, possibly via association with nucleolin
Authors: Iden Marissa , Fye Samantha , Li Keguo , Chowdhury Tamjid , Ramchandran Ramani , Rader Janet S. 
Published: May 2016

Abstract
The plasmacytoma variant translocation 1 gene (PVT1) is an lncRNA that has been designated as an oncogene due to its contribution to the phenotype of multiple cancers. Although the mechanism by which PVT1 influences disease processes has been studied in multiple cancer types, its role in cervical tumorigenesis remains unknown. Thus, the present study was designed to investigate the role of PVT1 in cervical cancer in vitro and in vivo. PVT1 expression was measured by quantitative PCR (qPCR) in 121 invasive cervical carcinoma (ICC) samples, 19 normal cervix samples, and a cervical cell line (SiHa). Further, we used targeted knockdown in conjunction with functional assays to examine PVT1's effects on cervical cancer cell proliferation, migration and invasion, apoptosis, and cisplatin resistance. Our results demonstrate that PVT1 expression is significantly increased in ICC tissue versus normal cervix. PVT1 knockdown in cervical cancer cell lines resulted in significantly decreased cell proliferation, migration and invasion. Further, apoptosis and cisplatin cytotoxicity were significantly increased in PVT1 siRNA-transfected cells. Finally, we show that PVT1 associates with Nucleolin protein and may aid in its stabilization of GADD45A mRNA providing a possible mechanism by which PVT1 overexpression drives cervical carcinogenesis.
Citation Format: Marissa Iden, Samantha Fye, Keguo Li, Tamjid Chowdhury, Ramani Ramchandran, Janet S. Rader. Overexpression of the lncRNA PVT1 contributes to the cervical cancer phenotype, possibly via association with nucleolin. [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 B10.
Abstract B14: Tanshinones suppress AURKA through up-regulation of miR-32 expression in non-small cell lung cancer
Authors: ma zhongliang , zhang bingjie , li yanli 
Published: May 2016

Abstract
Tanshinones which includes tanshinone I (T1), tanshinone IIA (T2A), and cryptotanshinone (CT), are the liposoluble constituent of Salia miltiorrhiza, AURKA, an oncogene, encodes a serine-threonine kinase which regulates mitotic processes in mammalian cells. Here, we reported that tanshinones mediate AURKA suppression partly through up-regulating the expression of miR-32, one of miR-25 family. We found that tanshinones could inhibit cell proliferation, promote apoptosis, and impede cell-cycle progression, thus performing an antineoplastic function in non-small cell lung cancer (NSCLC). Additionally, we demonstrated that tanshinones attained these effects in part by down-regulating AURKA, corroborating previous reports. Our results showed that in NSCLC, similar effects were obtained with knock-down of the AURKA gene by siRNA. We also verified that AURKA was the direct target of miR-32. we also found that miR-32 can promote the expression of Let-7 family, however, let-7 family down-regulates the level of miR-32. Collectively, our results demonstrated that tanshinones could inhibit NSCLC by suppressing AURKA via up-regulating the expressions of miR-25 family, let-7 family and other related miRNAs.
Note: This abstract was not presented at the conference.
Citation Format: zhongliang ma, bingjie zhang, yanli li. Tanshinones suppress AURKA through up-regulation of miR-32 expression 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 B14.
Abstract B20: miR-211 Functions as a metabolic switch in human melanoma cells
Authors: Mazar Joseph , Qi Feng , Lee Bongyong , Marchica John , Govindarajan Subramaniam , Shelley John , Li Jian-Liang , Ray Animesh , Perera Ranjan J. 
Published: May 2016

Abstract
The microRNA (miRNA) miR-211 negatively regulates genes that drive invasion of metastatic melanoma. Compared to normal human melanocytes, miR-211 expression is significantly reduced or absent in non-pigmented melanoma cells and lost during human melanoma progression. To investigate mechanisms of its tumor suppressor function, miR-211 was ectopically expressed in non-pigmented melanoma cells. Ectopic miR-211 expression destabilized hypoxia-inducible factor 1α (HIF-1α) and caused increased cell death during hypoxia. HIF-1α destabilization was correlated with down-regulation of a novel miR-211 target gene, pyruvate dehydrogenase kinase 4 (PDK4). We present evidence that resumption of miR-211 mediated down-regulation of PDK4 in melanoma cells caused hypoxia-induced cell death via HIF-1α destabilization. Thus the tumor suppressor miR-211 acts as a metabolic switch, and its loss is expected to promote cancer hallmarks in human melanomas.
Citation Format: Joseph Mazar, Feng Qi, Bongyong Lee, John Marchica, Subramaniam Govindarajan, John Shelley, Jian-Liang Li, Animesh Ray, Ranjan J. Perera. miR-211 Functions as a metabolic switch in human melanoma cells. [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 B20.
Abstract B21: A long noncoding RNA LINC00467 regulates autophagy in cancer
Authors: Pridham Kevin J. , Guo Sujuan , Sheng Zhi 
Published: May 2016

Abstract
Autophagy is a degradation pathway utilized by cells under stressful conditions such as nutrient deprivation or drug treatment to support extended survival. During this process, cellular components are broken down to macromolecules to be re-assimilated for consumption to sustain cell survival. With autophagy serving an important role between life and death for a cell, it has implications in not only maintaining homeostasis of normal cells but also the growth and survival of malignant cancer cells. Long noncoding RNAs (LncRNAs) are RNA transcripts longer than 200 nucleotides with no protein-coding potential and play an important role in the regulation of gene expression. Albeit certain LncRNAs are overexpressed in cancer with a strong correlation with cancer risk and prognosis, the relationship of LncRNAs and autophagy has not yet been extensively explored. Our previous work has identified LINC00467 (long intergenic noncoding RNA 00467 or C1orf97) as a potential autophagy regulator in chronic myeloid leukemia (CML) cells. We further hypothesized that LINC00467 is a common autophagy regulator in cancer. To test this hypothesis, we analyzed the gene expression pattern of this LncRNA using RT-PCR, monitored its expression in cancers by querying different gene expression databases, measured expression by RT-PCR in different cancer cell lines, and measured autophagy in cancer cells upon depletion of LINC00467. Our results show that (1) LINC00467 is expressed as two transcripts (733 and 797 nucleotides); (2) LINC00467 is ubiquitously expressed in different types of cancer; and (3) LINC00467 depletion activates autophagy in multiple cancer cell lines. This work will illuminate an otherwise unknown and new autophagy-regulatory pathway and will add a new dimension to our knowledge of the regulation of cancer cell survival and death. Of particular importance, this new autophagy regulatory pathway may provide new and effective therapeutic targets.
Citation Format: Kevin J. Pridham, Sujuan Guo, Zhi Sheng. A long noncoding RNA LINC00467 regulates autophagy in 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 B21.
Abstract B31: Bladder cancer patient urinary exosomes and tumors contain long noncoding RNA that may serve as therapeutic targets and biomarkers
Authors: Berrondo Claudia , Flax Jonathan , Siebert Aisha , Kucherov Victor , Rosenberg Alex , Fucile Christopher , Beckham Carla 
Published: May 2016

Abstract
While long non-coding RNA (lncRNA) play important roles in tumor biology including bladder cancer (BC), no previous studies have shown that lncRNAs in BC patient urinary exosomes (UEs) can function as biomarkers of disease. Exosomes are 30-150nm secreted membrane-bound vesicles that contain active biomolecules like: messenger(m)RNA, micro(mi)RNA, lncRNA and proteins generated from their cells of origin. In this study, we identified a panel of lncRNAs and mRNAs enriched in the UEs and tumors of BC patients, including the well-characterized lncRNA, HOTAIR. In order to elucidate if HOTAIR has a functional role in BC, we knocked it down in BC cell lines. Loss of HOTAIR resulted in reduced expression of known HOTAIR epithelial-to-mesenchyme transition (EMT) target genes, as well as reduced migration, and invasion using trans-well and 3-D culture assays. These data suggest that HOTAIR may serve as both a biomarker in UEs and as a potential therapeutic target. Critically, we RNA-Sequenced primary tumors, distal normal tissue (DNT) and UEs of BC patients and UEs from healthy volunteers (HV) to identify two novel lncRNAs, LINC00477 and LINC00940 enriched in BC patients' UEs and tumors. These candidate lncRNAs were confirmed with quantitative real time (qRT-PCR). Taken together, UE lncRNA content reflect the lncRNA content of BC tumors and may serve as biomarkers of disease. Further investigation is needed to validate the use of the lncRNAs presented in this study as biomarkers and putative therapeutic targets in relevant patient populations.
Citation Format: Claudia Berrondo, Jonathan Flax, Aisha Siebert, Victor Kucherov, Alex Rosenberg, Christopher Fucile, Carla Beckham. Bladder cancer patient urinary exosomes and tumors contain long noncoding RNA that may serve as therapeutic targets and biomarkers. [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 B31.
Abstract B38: Cancer-related circulating long noncoding RNAs in serous extracellular vesicles: Their characterization and potential application
Authors: Lei Dong , Wanrun Lin , Peng Qi , Midie Xu , Xiang Du 
Published: May 2016

Abstract
Background: Circulating nucleic acids (CNAs) are extracellular nucleic acids found in cell-free sera, plasma and other bodily fluids of healthy subjects and cancer patients. We have previously demonstrated that human serum or plasma contains microRNAs (miRNAs) and long non-coding RNA (lncRNAs) that are significantly up-regulated or down-regulated in various types of cancer and are of good diagnostic value for screening. The mechanisms underlying the stability of serum RNAs are unclear; lncRNAs may be protected by extracellular vesicles (EV) including apoptotic body (AB), microvesicle (MV) and exosome (EXO), as for circulating miRNAs. In order to find optimal method to evaluate the potential utility of circulating lncRNAs for cancer diagnosis or prognosis, more exploration should be undertook for the distribution of circulating lncRNAs.
Results: The shapes and sizes of three subgroups of extracellular vesicles, including AB, MV and EXO, were evaluated. NanoSight particle tracking analysis and transmission electron microscopy (TEM) showed the MVs, pelleted at 12, 000×g, were with the size range of 75-465 nm; and EXOs, pelleted at 120,000×g, with the size range of 45-205 nm. In serous vesicles of both colorectal cancer and healthy subjects, 17 of the 39 cancer-related lncRNAs were detected, including TDRG1, MEG3, DSCAM-AS1, 7SK, MIR31HG, CBR3-AS1, TUG1, BCAR4, EPB41L4A, PCA3, FAS-AS1, SUMO1P3, uc338, PRNCR1, PTENP1 and CUDR. The amount of most lncRNAs were higher in EXO than those in AB and MV. In addition, AB contains higher amount of most lncRNAs than MV.
Results: The shapes and sizes of three subgroups of extracellular vesicles, including AB, MV and EXO, were evaluated. NanoSight particle tracking analysis and transmission electron microscopy (TEM) showed the MVs, pelleted at 12, 000×g, were with the size range of 75-465 nm; and EXOs, pelleted at 120,000×g, with the size range of 45-205 nm. In sera of both colorectal cancer and healthy subjects, 16 out of the 39 cancer-related lncRNAs were detected. The amount of most lncRNAs were higher in EXO than those in AB and MV. In addition, AB contains higher amount of most lncRNAs than MV.
Conclusions: Among three types of vesicles in sera, EXOs were the richest reservoir for almost all measured lncRNAs, while the MVs contained the least amount of lncRNAs. EXOs, as their intercellular origin, have reasons to contain higher amount of lncRNAs among serous vesicles and seem to be the most promising research materials in the field of circulating lncRNA.
Citation Format: Dong Lei, Lin Wanrun, Qi Peng, Xu Midie, Du Xiang. Cancer-related circulating long noncoding RNAs in serous extracellular vesicles: Their characterization and potential application. [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 B38.
Abstract IA01: Divergent transcription and long noncoding RNA in cancer
Authors: Sharp Phillip A. 
Published: May 2016

Abstract
The processes of divergent transcription and RNA splicing control the synthesis of many long noncoding RNAs in mammalian cells. These RNAs could facilitate the binding of transcription factors and other complexes thus enhancing transcription of genes. Their existence suggests that nuclear RNA forms connectivity for location of regulatory complexes in cells. These probably change during the transformation process, perhaps accounting for some of the concordant changes in gene expression.
Citation Format: Phillip A. Sharp. Divergent transcription and long noncoding RNA in 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 IA01.
Abstract IA10: microRNAs and lncRNAs in mammalian physiology and cancer
Authors: Mendell Joshua T. 
Published: May 2016

Abstract
Gain- and loss-of-function of noncoding RNAs can potently influence cellular behavior in normal physiologic states and in diseases such as cancer. In particular, dysregulation of microRNA (miRNA) expression has been clearly shown to result in dramatic phenotypic consequences. We previously demonstrated extensive control of miRNA expression by well-characterized oncogenic and tumor suppressor networks including the MYC, KRAS, and p53 pathways. More recently, we have uncovered germline and somatic mutations in core miRNA processing components such as DROSHA and DICER in tumors. The analysis of novel mouse models with gain- and loss- of miRNA function has revealed potent, and often unexpected, consequences of dysregulated miRNA expression and activity in vivo. More recently, we have applied these same approaches to dissect novel mechanisms of long noncoding RNA (lncRNA) regulation and function in mammalian physiology and cancer. I will present our latest results related to the regulation and function of noncoding RNAs and how these findings may be exploited for the development of novel therapeutic approaches.
Citation Format: Joshua T. Mendell. microRNAs and lncRNAs in mammalian physiology and 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 IA10.