bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A14: microRNA-mediated interactions regulate established oncongenic pathways in cancer
Authors: Sumazin Pavel , Chiu Hua-Sheng , Califano Andrea 
Published: April 2013

Abstract
By analyzing gene expression data in gliobastoma in combination with matched microRNA profiles, we have uncovered a post-transcriptional regulation layer of surprising magnitude, comprising hundreds of thousands of microRNA -mediated interactions. These include ~7,000 genes whose transcripts act as microRNA ‘sponges’ and 148 genes that act through alternative, non-sponge interactions. Biochemical analyses in cell lines confirmed that this network regulates established drivers of tumor initiation and subtype, including PTEN, PDGFRA, RB1, VEGFA, STAT3, and RUNX1, suggesting that these interactions mediate crosstalk between canonical oncogenic pathways. RNA silencing of 13 microRNA-mediated PTEN regulators, whose locus deletions are predictive of PTEN expression variability, was sufficient to downregulate PTEN in a 3′ UTR-dependent manner and to increase tumor-cell growth rates. Thus, this microRNA-mediated network provides a mechanistic, experimentally validated rationale for the loss of PTEN expression in a large number of glioma samples with an intact PTEN locus. Recently, we extended this work to three other tumor types, showing that microRNA-mediated interactions propagate the effects of genetic alterations to regulate distal oncogenes and tumor suppressors in multiple cancers. Our results suggest that, although implemented by context-specific factors, hundreds of thousands of these interactions are context-independent.
Note: This abstract was not presented at the conference because the presenter was unable to attend.
Citation Format: Pavel Sumazin, Hua-Sheng Chiu, Andrea Califano. microRNA-mediated interactions regulate established oncongenic pathways in cancer [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr A14.
Abstract A16: MiR-22 down-regulation via epigenetic control in oral cancer cells
Authors: Wu Li-Wha 
Published: April 2013

Abstract
The deregulation of certain microRNAs has been associated with the progression and metastasis of various cancer types. DNA methylation in the CpG islands plays a crucial role in the down-regulation of tumor suppressor genes, including miRNAs. MiR-22 has been shown to be deregulated in several cancer types, including breast cancer and multiple myeloma. Using real-time RT-PCR analysis, we also found that miR22 was down-regulated in the majority of tested oral cancer cell lines and 70% of the clinical specimens when compared with their normal counterparts. Consistent with the notion that DNA methylation might play a role in the gene silencing, we did detect a putative CpG island (~ 1.2 kb in length) located upstream from the putative miR-22 transcription start site (+1) using two independent CpG island prediction softwares. Two oral cancer lines with low miR−22 expression were treated for 3–5 days with the indicated dose of 5′-azaC together with or without trichostatin A. Total RNA was isolated from the treated cells for real-time quantitative PCR analysis of miR-22 expression. The expression of miR-22 was significantly induced by either inhibitor. Combined treatment further enhanced the expression, suggesting the involvement of epigenetic control in the decreased expression of miR-22 in oral cancer cells. We first divided the putative CpG island into 5 regions and designed nested PCR primers for bisulfate sequencing PCR. We found that only regions 3 to 5 in the putative CpG island were subjected to be influenced by methylation in certain oral cancer lines. Since MeCP2 selectively binds to methylated CpG dinucleotides, chromatin immunoprecipition together with qPCR will be used to examine if MeCP2 would have increased binding to the identified methylated CpG sites. Second, quantitative methylation specific PCR (qMSP) will be used to measure the methylation levels of miR-22 genes in oral cancer tissues and their normal control using SYBR Green–based detection technology. Third, in vitro methylation and promoter-driven luciferase assay will be used to investigate whether DNA methylation plays a direct role in regulating miR-22 promoter activity and whether CpG island deletion affects the relative luciferase activity. Together, this study would implicate that the expression of miR-22 is controlled by epigenetic control in oral cancer cells. However, the exact nature of miR-22 in oral carcinogenesis remains to be characterized.
Citation Format: Li-Wha Wu. MiR-22 down-regulation via epigenetic control in oral cancer cells [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr A16.
Abstract A3: miR-31 and its host gene lncRNA LOC554202 are regulated by promoter hypermethylation in triple-negative breast cancer
Authors: Augoff Katarzyna , McCue Brian , Plow Edward F. , Sossey-Alaoui Khalid 
Published: April 2013

Abstract
Background: microRNAs have been established as powerful regulators of gene expression in normal physiological as well as in pathological conditions, including cancer progression and metastasis. Recent studies have demonstrated a key role of miR-31 in the progression and metastasis of breast cancer. Downregulation of miR-31 enhances several steps of the invasion-metastasis cascade in breast cancer, i.e., local invasion, extravasation and survival in the circulation system, and metastatic colonization of distant sites. miR-31 exerts its metastasis-suppressor activity by targeting a cohort of pro-metastatic genes, including RhoA and WAVE3. The molecular mechanisms that lead to the loss of miR-31 and the activation of its pro-metastatic target genes during these specific steps of the invasion-metastasis cascade are however unknown.
Results: In the present report, we identify promoter hypermethylation as one of the major mechanisms for silencing miR-31 in breast cancer, and in the triple-negative breast cancer (TNBC) cell lines of basal subtype, in particular. miR-31 maps to the intronic sequence of a novel long non-coding (lnc)RNA, LOC554202 and the regulation of its transcriptional activity is under control of LOC554202. Both miR-31 and the host gene LOC554202 are down-regulated in the TNBC cell lines of basal subtype and over-expressed in the luminal counterparts. Treatment of the TNBC cell lines with either a de-methylating agent alone or in combination with a de-acetylating agent resulted in a significant increase of both miR-31 and its host gene, suggesting an epigenetic mechanism for the silencing of these two genes by promoter hypermethylation. Finally, both methylation-specific PCR and sequencing of bisulfite-converted DNA demonstrated that the LOC554202 promoter-associated CpG island is heavily methylated in the TNBC cell lines and hypomethylated in the luminal subtypes.
Conclusion: Loss of miR-31 expression in TNBC cell lines is attributed to hypermethylation of its promoter-associated CpG island. Together, our results provide the initial evidence for a mechanism by which miR-31, an important determinant of the invasion metastasis cascade, is regulated in breast cancer.
Citation Format: Katarzyna Augoff, Brian McCue, Edward F. Plow, Khalid Sossey-Alaoui. miR-31 and its host gene lncRNA LOC554202 are regulated by promoter hypermethylation in triple-negative breast cancer [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr A3.
Abstract A33: The role of microRNA-181a in TGF-β-mediated breast cancer progression
Authors: Taylor Molly A. , Schiemann William P. 
Published: April 2013

Abstract
Transforming growth factor-beta (TGF-β) is a multifunctional cytokine that functions to inhibit breast cancer development in the normal mammary epithelium by inducing cell cycle arrest, and maintaining microenvironmental homeostasis through extracellular matrix (ECM) deposition and remodeling. Mammary tumorigenesis causes a loss in TGF-β-mediated cytostasis and leads to a switch in TGF-β function, whereby TGF-β promotes epithelial-mesenchymal transition (EMT), proliferation, invasion and metastasis. This switch in TGF-β function, from tumor suppressor to tumor promoter, is referred to as the “TGF-β paradox” and occurs through molecular mechanisms that remain incompletely understood. Moreover, this switch in TGF-β function is often accompanied by desmoplastic and fibrotic reactions, leading to the formation of a more rigid microenvironment, which in and of itself has been associated with tumor progression. We have shown that tissue compliance and extracellular matrix rigidity mediate how cells sense and respond to TGF-β. Indeed, we can recapitulate the “TGF-β paradox” by exposing metastatic breast cancer cells to compliant ECM signals, which reinstates the cytostatic activities of TGF-β. As a possible mechanism for the influence of matrix rigidity on TGF-β signaling, we sought to define the miRNA expression profiles induced by TGF-β in metastatic cells as compared to their non-metastatic counterparts when grown in either compliant or rigid conditions. We show that ECM rigidity regulates the miRNA expression signature induced by TGF-β in breast cancer cells. From this miRNA signature, we have identified the miR-181 family as a miR family that is highly upregulated in metastatic cells in response to TGF-β. Additionally, over-expression of a miR-181a mimic enhances TGF-β-mediated invasion. Conversely, treating cells with a hairpin inhibitor directed against miR-181a inhibits TGF-β-mediated invasion, EMT, and survival signaling. Furthermore, inhibition of miR-181a abrogates pulmonary outgrowth and enhances overall survival in vivo. Collectively, our findings identify the miR-181a family as a novel effector of TGF-β-driven tumor progression and suggest that measures capable of diminishing miR-181a levels may alleviate breast cancer progression.
[FY09-DOD-BCRP-Predoctoral Traineeship Award].
Citation Format: Molly A. Taylor, William P. Schiemann. The role of microRNA-181a in TGF-β-mediated breast cancer progression [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr A33.
Abstract A6: microRNA sequencing of AKXD recombinant inbred panel identifies miR-216b as a candidate metastasis suppressor in a murine model of breast cancer
Authors: Faraji Farhoud , Hu Ying , Goldberger Natalie , Wu Gang , Buetow Ken H. , Zhang Jinghui , Hunter Kent W. 
Published: April 2013

Abstract
Metastatic disease continues to be the primary cause of mortality in cancer. Using a combination of complex genetics, mouse models of breast cancer, and human epidemiology, our laboratory has demonstrated that germline polymorphism contributes to an individual's susceptibility to metastasis. In the current study, we have used the AKXD recombinant inbred panel, which is derived from inbred mice of metastasis resistant, DBA, and metastasis-prone, AKR, genetic backgrounds, to identify microRNAs whose expression is associated with metastasis. microRNA sequencing of tumor tissue from the progeny of AKXD x Polyoma Middle-T mice demonstrated that the expression of the miR-216/217 cluster is significantly negatively correlated with pulmonary metastases in the AKXD panel. Linkage analysis demonstrated a significant association between the miR-216/217 locus and the DBA allele, suggesting that the difference in expression is inherited rather than somatically acquired. Finally, we show that ectopic expression of miR-216b in murine mammary tumor cells suppresses pulmonary metastasis without significantly impacting primary tumor growth in vivo. These findings suggest that miR-216b is an inherited modifier of metastasis with metastasis suppressing activity in a mouse model of breast cancer.
Citation Format: Farhoud Faraji, Ying Hu, Natalie Goldberger, Gang Wu, Ken H. Buetow, Jinghui Zhang, Kent W. Hunter. microRNA sequencing of AKXD recombinant inbred panel identifies miR-216b as a candidate metastasis suppressor in a murine model of breast cancer [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr A6.
Abstract B4: MicroRNAs differentially expressed in preoperative human serum of ovarian cancer
Authors: Chao Angel , Wang Tzu Hao , Chen Hua-Chien , Chen Shu-Jen , Lai Chyong-Huey 
Published: April 2013

Abstract
MicroRNAs (miRNAs) have been reported to play important regulatory roles in many biological processes and tumorigenesis. To investigate the roles of serum miRNAs in patients before tumor bulk was surgically removed from ovarian cancer patients, we utilized miRNA real-time QPCR profiling technology to characterize the miRNAs in pre-operative and postoperative sera. Six pairs of sera were analyzed using 270 miRNA SyberGreen probes. Upregulation of miR187, miR499-3p, miR548c-5p, miR1, miR107, miR125a-5p, miR18b were identified in the preoperative sera. Targetscan was utilized to identify Dab2 as the target gene of miR187. In vitro studies of SKOV3 cells showed that ectopic expression of miR187 suppressed Dab2 and resulted in increased cell proliferation. We concluded that miR187 may be a potential biomarker in sera of ovarian cancer patients. Further studies with larger sample sizes are warranted to validate our results.
Citation Format: Angel Chao, Tzu Hao Wang, Hua-Chien Chen, Shu-Jen Chen, Chyong-Huey Lai. MicroRNAs differentially expressed in preoperative human serum of ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr B4.
Abstract IA10: Spreading of X-chromosome inactivation via a hierarchy of defined Polycomb stations
Authors: Pinter Stefan F. , Pinter Stefan F. , Pinter Stefan F. , Jeon Yesu , Jeon Yesu , Jeon Yesu , Ohsumi Toshiro K. , Ohsumi Toshiro K. , Borowsky Mark , Borowsky Mark , Lee Jeannie T. , Lee Jeannie T. , Lee Jeannie T. , Sadreyev Ruslan I. , Sadreyev Ruslan I. , Sadreyev Ruslan I. , Yildirim Eda , Yildirim Eda , Yildirim Eda 
Published: April 2013

Abstract
X-chromosome inactivation (XCI) achieves dosage balance in mammals by repressing one of two X-chromosomes in females. During XCI, the long noncoding Xist RNA and Polycomb proteins spread along the inactive X (Xi) to initiate chromosome-wide silencing. Although inactivation is known to commence at the X-inactivation center (Xic), how it propagates remains unknown. We have examined allele-specific binding of Polycomb repressive complex 2 (PRC2) and chromatin composition during XCI, and generate a chromosome-wide profile of Xi and Xa (active X) at nucleosome-resolution. Initially, Polycomb proteins are localized to a limited number of sites along the X. As Xist RNA spreads in cis during the XCI process, thousands of additional sites are recruited. PRC2 and H3K27 methylation spread along a gradient in an Xi-specific manner not seen on autosomes. Our findings suggest that XCI is governed by a hierarchy of defined Polycomb stations that spread H3K27 methylation in cis.
Citation Format: Stefan F. Pinter, Yesu Jeon, Toshiro K. Ohsumi, Mark Borowsky, Jeannie T. Lee, Ruslan I. Sadreyev, Eda Yildirim. Spreading of X-chromosome inactivation via a hierarchy of defined Polycomb stations [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr IA10.
Abstract IA17: Functional genomics, small RNAs and cancer
Authors: Hahn William C. 
Published: April 2013

Abstract
Efforts to sequence cancer genomes have begun to uncover comprehensive lists of genes altered in cancer. Unfortunately, the complexity and sheer volume of data that emerges from these efforts has made dissecting the underlying biology of cancer difficult. In addition, the number and types of candidate targets that require functional validation in vivo represent a significant barrier to using this information as a starting point for drug development programs, since many do not represent targets amenable to traditional small molecule or antibody-based therapeutic approaches. To address this problem, we have combined comprehensive analyses of cancer genomes with novel materials science to develop a platform that enables the ready in vivo validation of cancer targets. Specifically, we have developed a screening platform to perform loss of function screens at genome scale and have applied this in a massively parallel manner to screen several hundred full characterized cancer cell lines. We have combined the outputs of these screens with data emerging from the study of cancer genomes to identify candidate oncogenes. To credential these targets in vivo, we have helped develop novel nanocomplexes formed from siRNA bound to tandem peptides containing tumor-penetrating, endosomal escape and siRNA-binding domains that permit deep penetration in tumor. We use these nanoparticles to target a hitherto undiscovered ovarian cancer oncogene, ID4, an undruggable transcriptional regulator, and show that these tumor-penetrating nanocomplexes induced complete suppression of tumor growth and significant improvement of survival. Taken together, these studies provide a platform for the discovery and initial validation of candidate cancer targets.
Citation Format: William C. Hahn. Functional genomics, small RNAs and cancer [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr IA17.
Abstract IA18: Mechanisms of miRNA mediated cellular reprogramming
Authors: Morrisey Edward 
Published: April 2013

Abstract
Recent evidence has indicated that miRNAs have the ability to promote dramatic changes in cell fate including pluripotent stem cell reprogramming. Certain miRNA clusters including miR302/367 are highly expressed in embryonic stem cells and when over-expressed can convert fibroblasts to induced pluripotent stem cells. Moreover, recent publications have shown that certain miRNAs can directly convert fibroblasts to neurons indicating that this technique may be widely applicable to other cell lineages. Despite these intriguing results, little is understood about the molecular mechanism underlying miRNA mediated reprogramming. Since miRNAs can target hundreds of mRNAs, identification of specific targets as well as molecular pathways affected will require multiple approaches. Data will be presented on how our lab is using systems biology and genomic approaches to decipher the underlying mechanism of miRNA-mediated cellular reprogramming.
Citation Format: Edward Morrisey. Mechanisms of miRNA mediated cellular reprogramming [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr IA18.
Abstract IA21: Long noncoding RNAs as drug targets
Authors: Wahlestedt Claes Robert 
Published: April 2013

Abstract
Much of the mammalian genome is transcribed into non-coding RNAs of different categories. This lecture will primarily be concerned with natural antisense transcripts (NATs) most of which are long noncoding RNAs. NATs are found in most gene loci and regulate gene expression through several distinct mechanisms including chromatin modifications. Inhibition/perturbation of endogenous NATs by modified oligonucleotides called AntagoNATs, in vitro or in vivo, reveals concordant or discordant regulation and results in down- or up-regulation of conventional (protein-coding) gene expression, respectively. Evidence will be presented that AntagoNATs can potently induce locus-specific and reversible modulation of gene expression associated with alterations in chromatin marks.
Citation Format: Claes Robert Wahlestedt. Long noncoding RNAs as drug targets [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr IA21.
Abstract IA4: Linking RNA to human health and disease
Authors: Cabili Moran , Lander Eric , Sabeti Pardis , Regev Aviv , Rinn John L. , Rinn John L. , Rinn John L. , Trapnell Cole , Trapnell Cole , Goff Loyal , Goff Loyal , Broadbent Kate , Broadbent Kate , Guttman Mitchell 
Published: April 2013

Abstract
In the 50 years since RNA was identified as a central component in the flow of genetic information, it has become increasingly clear that RNA is more than a mere messenger and instead performs vast and diverse functions. Numerous studies have revealed that the mammalian genome is pervasively transcribed, giving rise to many thousands of non-coding transcripts including a class of long intergenic noncoding RNAs (lincRNAs). Raising the question of what do lincRNAs do?
To address this question we have developed a ‘guilt by association’ to ‘predict’ lincRNA functions leading to hypothesis driven experimentation. Our guilt by association method pointed to a clear connection of lincRNAs and numerous cellular pathways ranging from pluripotency, cancer, adipogenesis to parasitology. Experimental perturbation experiments have unraveled a myriad of functional roles for lincRNAs in these pathways. Together, these results point to key regulatory roles for lincRNAs across diverse biological pathways and diseases, with a common theme of interfacing with and modulating protein regulatory complexes.
Citation Format: Moran Cabili, Eric Lander, Pardis Sabeti, Aviv Regev, John L. Rinn, Cole Trapnell, Loyal Goff, Kate Broadbent, Mitchell Guttman. Linking RNA to human health and disease [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr IA4.
Abstract IA7: Unraveling the complexities of p63 in cancer and stem cells
Authors: Flores Elsa R. 
Published: April 2013

Abstract
Aberrant expression of microRNAs (miRNAs) and the enzymes that control their processing have been reported in multiple biological processes including in cancer and the regulation of stem cells, but the mechanisms governing this are not clearly understood. We have generated conditional knockout mice that allow the functional separation of TAp63 and ΔNp63. Using the TAp63 conditional knock out mouse model, we found that TAp63 suppresses tumorigenesis and metastasis through coordinate transcriptional regulation of Dicer and miR-130b. Interestingly, we have recently found that ΔNp63 also plays an important role in miRNA processing by transcriptionally activating DGCR8. In turn, DGCR8 is required for processing of key miRNAs that repress genes required for stem cell pluripotency, Oct4, Sox2, and Nanog. Strikingly, epidermal cells derived from ΔNp63 deficient mice express markers of pluripotency at levels comparable to mouse embryonic stem cells. Moreover, these cells exhibit characteristics of stem cells that can self-renew and can differentiate into multiple cell fates in vitro and in vivo. Our data reveal a novel role for ΔNp63 in the commitment to epidermal differentiation through transcriptional regulation of DGCR8 and downstream modulation of key miRNAs required to maintain stem cell pluripotency. Taken together, our data show that p63 plays critical roles in regulating miRNAs in multiple biological processes.
Citation Format: Elsa R. Flores. Unraveling the complexities of p63 in cancer and stem cells [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr IA7.