bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3435: Profiling miRNAs in breast epithelial progenitor cells during branching morphogenesis and EMT in 3D culture
Authors: Briem Eirikur , Hilmarsdottir Bylgja , Budkova Zuzana , Ingthorsson Saevar , Magnusson Magnus K. , Gudjonsson Thorarinn 
Published: July 2017

Abstract
In this study we investigate the role of miRNA-203a in branching morphogenesis and epithelial to mesenchymal transition (EMT) in breast cell lines. D492 is a breast epithelial cell line with stem cell properties. D492 generates luminal- and myoepithelial cells and in 3D culture forms structures reminiscent of terminal duct lobular units of the breast. When cocultured with endothelial cells subset of D492 cells undergo EMT as evidenced by spindle shape morphology, E- to N cadherin switch and loss of keratin expression. We have established an endothelial-induced mesenchymal subline from D492 referred to as D492M. Here we use D492 and D492M as a model to investigate miRNA expression patterns during different stages of branching and in EMT. We performed small RNA-sequencing on D492 and D492M in 3D cultures. We were able to pinpoint miRNAs that are associated with epithelial integrity and suppressing EMT. We have recently shown that miRNA-200c-141 convert D492M back to the epithelial phenotype (Hilmarsdottir et al. G&D 2015). MiRNA-203a is also down-regulated in D492M. Here we overexpress miRNA-203a in D492 and D492M. Methylation analysis reveal that the promoter area of miRNA-203a is not methylated in D492M. When miRNA-203a is overexpressed in D492M, cells change phenotype from elongate, mesenchymal-like phenotype to more cuboidal epithelioid phenotype, show reduced cell proliferation, less ability to form colonies in low attachment cultures, less ability to migrate and reduced invasion capability. When D492MmiRNA-203a is co-cultured with endothelial cells in 3D culture they partially regain the ability to form branching structures similar to D492. D492MmiRNA-203a show reduced expression of EMT transcription factors SNAI2 and ZEB1. When cultured on transwell filters, D492M forms stratified squamous epithelial layer while D492MmiRNA-203a form single squamous layer. In conclusion, miRNA-203a induces partial epithelial phenotype in D492M as evidenced by morphology and marker expression. We also conclude that three dimensional cultures of D492 and D492M work well as a model system to investigate miRNA expression during branching morphogenesis and in EMT.
Citation Format: Eirikur Briem, Bylgja Hilmarsdottir, Zuzana Budkova, Saevar Ingthorsson, Magnus K. Magnusson, Thorarinn Gudjonsson. Profiling miRNAs in breast epithelial progenitor cells during branching morphogenesis and EMT in 3D culture [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3435. doi:10.1158/1538-7445.AM2017-3435
Abstract 3454: Autophagy governs tumorigenic effects following mitotic slippage
Authors: Crasta Karen C. , Cheng Bing , Guo Ke 
Published: July 2017

Abstract
Antimitotic drugs are often administered as first-line chemotherapy in several malignancies. However, their clinical success is often limited by acquired chemoresistance and disease relapse. The anti-proliferative basis of these drugs is induction of mitotic arrest culminating in cell death. Mitotic slippage occurs when cells exit mitosis and “slip” into interphase without chromosome segregation and cytokinesis. Little is known about how cells post-slippage influence outcome of treatment. Here, we demonstrate that post-slippage cells exhibit paracrine pro-tumourigenic potential following senescence and senescence-associated secretory phenotype development. This occurs in an autophagy-p53 axis-dependent manner, with autophagic inhibition in post-slippage cells bypassing senescence and leading to cell death. Indeed, the autophagy inhibitor Chloroquine and microtubule poisons synergistically inhibited tumour growth in mice. Hence, regimens targeting the senescence phenotype could provide a potential effective combinatorial strategy with antimitotic drugs. Sensitivity to this combinatorial treatment was dependent on p53 status, an important factor to consider before treatment.
Citation Format: Karen C. Crasta, Bing Cheng, Ke Guo. Autophagy governs tumorigenic effects following mitotic slippage [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3454. doi:10.1158/1538-7445.AM2017-3454
Abstract 3461: The Nek2 mitotic kinase drives centrosome amplification, mitotic dysfunction, and invasion in mammary epithelial and breast cancer cells
Authors: Rivera-Rivera Yainyrette , Marina Mihaela , Lee Miyoung , Saavedra Harold I. 
Published: July 2017

Abstract
Despite findings reported by The Cancer Genome Atlas (TCGA) that the most common human tumors have undergone at least one genomic doubling, the roles of polyploidy and chromosome instability (CIN) in cancer are poorly understood. Defective mitosis, and centrosome amplification (CA) are major sources of CIN, which generally associates with poor prognosis of patients. Prevalence of CA and CIN in hormone receptor negative (ER-PR-Her2- or ER-PR-Her2+) breast cancer patients, who have the poorest outcomes among all intrinsic subtypes, suggest that CA and CIN play major roles in the disease. CA in breast cancers correlates with poor survival, metastasis and high tumor grade, suggesting roles in tumor progression. Our laboratory, using an inducible K-RasG12D transgenic mouse that directed its expression to mammary epithelial cells, demonstrated CA appeared in precancerous mammary epithelial lesions, suggesting a role in tumor initiation. Despite these observations, the role of CA as cancer driver or promoter has not been tested experimentally. To understand that role, drivers of CA in cancer must be identified, and our laboratory showed that dysregulated E2F1, E2F2 and E2F3a, and their mitotic targets, including Nek2, TTK, and SgoI sustain CA and CIN in mammary epithelial and breast cancer cells. In fact, orthotopic models of breast cancer demonstrated that silencing of E2F3 leads to slow tumor growth that correlates with reduced mitosis, CA and Nek2 levels. We find that overexpression of the E2F target Nek2 in non-transformed mammary epithelial cells results in large acinar structures, CA, CIN, and changes in relevant EMT markers that include vimentin. Our findings indicate that deregulated E2F pathway contribute to mammary tumorigenesis in part by deregulating kinases that control mitosis, including Nek2, and in turn these affect mitotic progression, CIN, EMT and invasion. Thus, centrosome/kinases downstream of the E2F pathway may represent future targets for intervention in highly-malignant HR- breast cancers.
Citation Format: Yainyrette Rivera-Rivera, Mihaela Marina, Miyoung Lee, Harold I. Saavedra. The Nek2 mitotic kinase drives centrosome amplification, mitotic dysfunction, and invasion in mammary epithelial and breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3461. doi:10.1158/1538-7445.AM2017-3461
Abstract 3478: Expression of the transcribed ultraconserved region Uc.63+ in prostate cancer
Authors: Sekino Yohei , Goto Keisuke , Honma Ririno , Shigematsu Yoshinori , Sakamoto Naoya , Sentani Kazuhiro , Oue Naohide , Teishima Jun , Matsubara Akio , Yasui Wataru 
Published: July 2017

Abstract
Prostate cancer (PCa) is the most prevalent cancer among men and the second leading cause of cancer related death in western world. Currently, there is a lack of effective treatment options for advanced PCa. Understanding the molecular mechanisms in prostate cancer development and progression would allow the identification of novel prognostic markers or therapeutic targets. The transcribed-ultraconserved regions (T-UCRs) are novel class of noncoding RNAs that are absolutely conserved (100%) between orthologous regions of the human, rat and mouse genomes. Some studies showed that T-UCRs exhibit distinct profiles in various human cancers. We examined the expression profile of representative 26 T-UCRs using qRT-PCR in 12 PCa tissues and 10 non-neoplastic prostate tissues, and found that the expression of Uc.63+ was higher in PCa tissues than that in non-neoplastic tissues. Further analysis revealed that the expression of Uc.63+ significantly correlated with higher PSA levels (p = 0.007) and higher Gleason score (p &lt; 0.001). In order to verify biological function of Uc.63+ in PCa, we firstly transfected Uc.63+ expression vector into LNCaP cells expressing low level of Uc.63+. MTT assay and wound healing assay revealed that overexpression of Uc.63+ significantly increased the cell growth and migration. We also confirmed that downregulation of Uc.63+ using siRNA in DU145 and PC3 expressing high level of Uc.63+. Knockdown of Uc.63+ decreased the cell growth and migration. A recent report indicates that T-UCRs may act as endogenous competing RNA. miR-130b was found to have binding sites within the Uc.63+ using online software. We examined the expression of miR-130b by qRT-PCR in PCa tissues and non-neoplastic prostate tissues. We found a significant downregulation of miR-130b in PCa tissues compared with non-neoplastic prostate tissues, which figured out that there was a significant inverse correlation between Uc.63+ and miR-130b in PCa (p = 0.002). The expression of miR-130b in LNCaP was higher than that in DU145 and PC3. It has been shown that MMP2 is a direct target of miR-130b. Western blot analysis and qRT-PCR revealed that MMP2 expression was higher in LNCaP cells transfected with Uc.63+ expression than that in LNCaP cells transfected with empty vector. These results suggest that Uc.63+ may contribute to the progression of PC through miR-130b interaction.
Citation Format: Yohei Sekino, Keisuke Goto, Ririno Honma, Yoshinori Shigematsu, Naoya Sakamoto, Kazuhiro Sentani, Naohide Oue, Jun Teishima, Akio Matsubara, Wataru Yasui. Expression of the transcribed ultraconserved region Uc.63+ in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3478. doi:10.1158/1538-7445.AM2017-3478
Abstract 3481: Leveraging protein coding gene expression profiles to accurately impute lncRNA transcriptome of cancer cells
Authors: Nath Aritro , Geeleher Paul , Huang R. Stephanie 
Published: July 2017

Abstract
Long noncoding RNAs (lncRNAs) represent a large, diverse and tissue-specific class of transcripts that are involved in gene regulation. Recent large-scale cancer sequencing efforts indicate that lncRNAs are an important component of the cancer transcriptome, and may play a critical role in carcinogenesis and drug sensitivity. Accurate profiling of lncRNAs however remains a challenge owing to significantly lower expression levels than mRNA, requiring deep paired-end total RNA sequencing, which can be prohibitively expensive. Additionally, previous generation microarrays that constitute a vast majority of GEO and ArrayExpress datasets do not provide comprehensive lncRNA coverage.
Here we propose a lncRNA expression imputation (LEXI) framework to reconstruct the lncRNA transcriptome of cancer cells using their mRNA expression profiles. Our goal is to provide a tool that enables the harnessing of enormous wealth of publicly available cancer mRNA datasets and discover novel lncRNAs associated with carcinogenesis and drug sensitivity. The LEXI approach is based on learning patterns of mRNA expression associated with each lncRNA across a diverse cohort of cancer cells and then predict lncRNA expression profile of uncharacterized cells.
We developed LEXI by evaluating the performance of various machine-learning algorithms benchmarked in a cross-validation study across a cohort of 675 cancer cell lines and 9755 pan-cancer tissues. We adapted the LEXI framework based on optimal performance and computation time and show that LEXI accurately predicts lncRNA expression profiles in both cell lines and tissues. To demonstrate the utility of LEXI, we reconstruct the lncRNA transcriptome of over 1000 cell lines and 2000 TCGA samples, and compare with RNAseq measured lncRNA levels in corresponding samples. We further show expression levels of MALAT1, HOTAIR, CCAT1 and other established cancer-associated lncRNAs are accurately predicted across cancer types, and can be used to discover novel associations in uncharacterized phenotypes. LEXI will be available as a free resource for researchers to easily obtain lncRNA profiles using their own mRNA data.
Citation Format: Aritro Nath, Paul Geeleher, R. Stephanie Huang. Leveraging protein coding gene expression profiles to accurately impute lncRNA transcriptome of cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3481. doi:10.1158/1538-7445.AM2017-3481
Abstract 3491: A role for the long non-coding RNA GHRLOS in cancer
Authors: Shah Esha T. , Jeffery Penny , Thomas Patrick , Seim Inge , Chopin Lisa 
Published: July 2017

Abstract
Long non-coding RNA (lncRNA) genes are abundant in the human genome, and many are now recognized as oncogenes and/or tumor suppressors. We previously characterized the structure of GHRLOS, an antisense gene on the opposite strand of the multifunctional ghrelin gene (GHRL), however, its expression and function in disease has not been described.
To this end, using The Cancer Genome Atlas (TCGA) data set, we revealed that GHRLOS is differentially expressed in a number of cancers. In particular, expression was elevated in endometrial cancer (1.2 - fold; P = 7.1 x 10-3 Welch's two-sample t-test; n = 24 vs. n = 175) and prostate cancer (1.2-fold; P = 3.7 x 10-6; n = 52 vs. n = 498) compared to normal tissues. Using qRT-PCR (and commercial cDNA panels) we confirmed that GHRLOS expression was upregulated in endometrial cancer (1.96-fold, P = 0.005 Welch’s two-sample t-test, n = 5 vs. n = 17) and prostate cancer (2.46-fold, P = 0.0045 Welch’s two-sample t-test, n = 5 vs. n = 21) compared to normal tissues.
Initial studies, using siRNA designed to silence endogenous GHRLOS expression, significantly reduced cell migration in the PC3 prostate cancer cell line (0.47-fold change, P = 0.042 Kruskal-Wallis test, n = 2) conversely, preliminary data using forced GHRLOS overexpression increased migration and proliferation.
Taken together, we show that the long non-coding RNA GHRLOS is differentially expressed in tumor tissue and regulates cell migration and proliferation; possibly by modulating alternative splicing of the overlapping, multifunctional ghrelin gene locus. Targeting GHRLOS could provide a valuable and novel way to target the ghrelin axis in disease. Ongoing studies aim to validate in vitro functional results in complementary mouse xenograft models and identify genes and pathways regulated by this novel lncRNA.
Citation Format: Esha T. Shah, Penny Jeffery, Patrick Thomas, Inge Seim, Lisa Chopin. A role for the long non-coding RNA GHRLOS in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3491. doi:10.1158/1538-7445.AM2017-3491
Abstract 3499: Differentially expressed small noncoding RNAs in triple-negative breast cancer
Authors: Koduru Srinivas V. , Tiwari Amit K. , Leberfinger Ashley , Hazard Sprague W. , Kawasawa Yuka Imamura , Mahajan Milind , Ravnic Dino J. 
Published: July 2017

Abstract
Cancer is the second leading cause of death in the United States and is a major public health concern worldwide. Basic, clinical and epidemiological research is leading to improved cancer detection, prevention, and outcomes. Recent technological advances have allowed unbiased and comprehensive screening of genome-wide gene expression. Small non-coding RNAs (sncRNAs) have been shown to play an important role in biological processes and could serve as a diagnostic, prognostic and therapeutic biomarker for specific diseases. Recent findings have begun to reveal and enhance our understanding of the complex architecture of sncRNA expression including miRNAs, piRNAs, sn/snoRNAs and their relationships with biological systems. We used publicly available small RNA sequencing data that was derived from 24 triple negative breast cancers (TNBC) and 14 adjacent normal tissue samples to remap various types of sncRNAs. We found a total of 55 miRNAs were aberrantly expressed (p&lt;0.005) in TNBC samples (8 miRNAs upregulated; 47 downregulated) compared to adjacent normal tissues whereas the original study reported only 25 novel miRs. In this study, we used pathway analysis of differentially expressed miRNAs which revealed TGF-beta signaling pathways to be profoundly affected in the TNBC samples. Furthermore, our comprehensive re-mapping strategy allowed us to discover a number of other differentially expressed sncRNAs including piRNAs, sn/snoRNAs, rRNAs, miscRNAs and nonsense-mediated decay RNAs. We believe that our sncRNA analysis workflow is extremely comprehensive and suitable for discovery of novel sncRNAs changes, which may lead to the development of innovative diagnostic and therapeutic tools for TNBC.
Citation Format: Srinivas V. Koduru, Amit K. Tiwari, Ashley Leberfinger, Sprague W. Hazard, Yuka Imamura Kawasawa, Milind Mahajan, Dino J. Ravnic. Differentially expressed small noncoding RNAs in triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3499. doi:10.1158/1538-7445.AM2017-3499
Abstract 3504: High expression of lncRNA-ATB and miR-21 as a biomarker in human hepatocellular carcinoma
Authors: Lee Eunhye , Kim Gyeonghwa , Jang Se Young , Choi Yong-Hun , Lee Yu Rim , Tak Won Young , Kweon Young Oh , Park Soo Young , Hur Keun 
Published: July 2017

Abstract
Non-coding RNAs (ncRNAs) including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have emerged as novel gene-regulators. The aim of this study was to determine the clinical relevancies of 2 lncRNAs (lncRNA-ATB and MEG3) and 2 miRNAs (miR-21 and miR-31) in hepatocellular carcinoma (HCC). We analyzed clinical specimens from 100 pairs of HCC and matched normal liver (NL) tissues. MiRNAs and lncRNAs expression levels were evaluated by quantitative real-time PCR. In addition, we determined the clinical significance of the ncRNAs expression in matching tissue and serum exosome samples from HCC patients. MiR-21 significantly increased in HCC (P&lt;0.01) compared to corresponding NL tissues. LncRNA-ATB was significantly up-regulated in HCC (P&lt;0.05); however, lncRNA-MEG3 was down-regulated in HCC (P&lt;0.05) tissues. In addition, expression of miR-21 and lncRNA-ATB was significantly associated with the tumor size and poor prognosis of HCC patients. More importantly, expression of serum exosomal lncRNA-ATB and miR-21 was more significantly associated with HCC progression and poor patients survival compared to its’ tissue expression. We conclude that non-coding RNAs (lncRNA-ATB and miR-21) expression has the potential to serve as biomarkers for prognosis and targeted therapy in HCC patients.
Citation Format: Eunhye Lee, Gyeonghwa Kim, Se Young Jang, Yong-Hun Choi, Yu Rim Lee, Won Young Tak, Young Oh Kweon, Soo Young Park, Keun Hur. High expression of lncRNA-ATB and miR-21 as a biomarker in human hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3504. doi:10.1158/1538-7445.AM2017-3504
Abstract 3510: A role for the Ewing’s sarcoma breakpoint protein EWS in ERG-induced prostate tumorigenesis
Authors: Kedage Vivekananda , Selvaraj Nagarathinam , Nicholas Taylor R. , Budka Justin A. , Jerde Travis J. , Hollenhorst Peter C. 
Published: July 2017

Abstract
The TMPRSS2-ERG gene fusion occurs in one-half of prostate tumors and results in expression of ERG, an ETS family transcription factor that promotes prostate tumorigenesis. Another 5-10% of prostate tumors have similar rearrangements that result in over-expression of other ETS family members such as ETV1, ETV4, and ETV5. However, not all ETS family members are oncogenic, and normal prostate cells express at least 15 of these other ETS factors. Therefore, it is important to understand mechanisms that differentiate oncogenic ETS factors from non-oncogenic ETS factors. We have recently discovered that ERG, ETV1, ETV4, and ETV5, and no other ETS factor can directly bind the protein EWS. This is striking, as EWS is fused to various ETS factors in the chromosomal rearrangements that cause Ewing’s sarcoma. We demonstrate that fusion of EWS to any ETS protein is sufficient for that protein to function like ERG in prostate cells. Furthermore, the EWS-ERG interaction is required for ERG to activate an oncogenic gene expression program and for ERG-mediated tumorigenesis. Therefore, these findings reveal a conserved oncogenic mechanism for prostate cancer and Ewing’s sarcoma. In prostate cancer, aberrant over-expression of an ETS factor that naturally interacts with EWS, brings EWS to ETS-bound regions. In Ewing’s sarcoma this interaction is forced by the presence of an EWS/ETS fusion protein. Therefore, this model predicts that treatments that target EWS function would be effective in both types of cancer.
Citation Format: Vivekananda Kedage, Nagarathinam Selvaraj, Taylor R. Nicholas, Justin A. Budka, Travis J. Jerde, Peter C. Hollenhorst. A role for the Ewing’s sarcoma breakpoint protein EWS in ERG-induced prostate tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3510. doi:10.1158/1538-7445.AM2017-3510