bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 524: Analysis of long non-coding RNA expression and function in a mouse model of glioblastoma
Authors: Myskiw Chad , Kadri Sabah , Ke Eugene , Shishkin Alex , Friedmann-Morvinski Dinorah , Soda Yasushi , Guttman Mitchell , Verma Inder 
Published: May 2015

Abstract
Glioblastoma (GBM) is the most common adult brain tumor and represents one of the most treatment refractory cancers. Although significant progress has been made in understanding the coding genomic alterations associated with GBM, patient survival rarely exceeds 12-14 months following diagnosis. Long non-coding RNAs (lncRNAs) are RNA species generally classified as &gt; 200 base-pairs in length that lack protein coding potential and therefore exert their function as RNA. Several lncRNAs have been shown to play important roles in cancer biology. Despite this, the role of lncRNAs in cancer, and GBM in particular, remains relatively uncharacterized. We hypothesize that lncRNAs are differentially expressed in GBM and contribute to the pathogenesis of this disease.
Using next generation sequencing, we have identified lncRNAs expressed in our mouse model of GBM, initiated by lentivirus-mediated expression of oncogenic Ras and a shRNA targeting p53. This resulted in the identification of 818 putative lncRNAs, the majority of which represent novel, uncharacterized transcripts. The majority of the lncRNAs identified were intergenic and not associated with any known protein coding gene. Of the total lncRNAs, 44% were differentially expressed in tumor tissue compared to normal mouse brain. Expression of a subset of these differentially expressed lncRNAs was validated by real-time PCR. Expression of several of these validated lncRNAs could be altered by direct activation of oncogenic signaling in normal mouse neuroprogenitor cells and astrocytes. Using a combination of computational and molecular biology approaches, we will identify candidate lncRNAs to test in functional assays for their role in glioblastoma biology.
Citation Format: Chad Myskiw, Sabah Kadri, Eugene Ke, Alex Shishkin, Dinorah Friedmann-Morvinski, Yasushi Soda, Mitchell Guttman, Inder Verma. Analysis of long non-coding RNA expression and function in a mouse model of glioblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 524. doi:10.1158/1538-7445.AM2014-524
Abstract 5243: MicroRNAs-449a and -449b exhibit tumor suppressive effects in retinoblastoma
Authors: Jones Aunica A. , Martin Alissa , Bryar Paul , Mets Marilyn , Weinstein Joanna , Zhang Gang , Laurie Nikia A. 
Published: May 2015

Abstract
MicroRNAs (miRNAs) are short, non-coding RNAs that act by inhibiting target genes. Specific individual miRNAs have now been identified which have confirmed effects in cancer, and some miRNAs can act as either tumor suppressors or as oncogenes by exerting effects on important regulatory cellular pathways. The purpose of our study is to illustrate the relationship between the expressions of miRs-449a and -449b to retinoblastoma proliferation and apoptosis. We show that there is an inhibitory effect of miRs-449a and -449b in retinoblastoma by demonstrating significantly impaired proliferation and increased apoptosis of tumor cells when these miRNAs are overexpressed. This study suggests that these miRNAs could serve as viable therapeutic targets for retinoblastoma treatment. We also report the utility of combining overexpression of miRs-449a and -449b with broad-based chemotherapy drugs that are currently being used to treat retinoblastoma patients.
Citation Format: Aunica A. Jones, Alissa Martin, Paul Bryar, Marilyn Mets, Joanna Weinstein, Gang Zhang, Nikia A. Laurie. MicroRNAs-449a and -449b exhibit tumor suppressive effects in retinoblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5243. doi:10.1158/1538-7445.AM2014-5243
Abstract 5244: MicorRNA-27a functions as a tumor suppressor in colorectal cancer through targeting SPGG1 and Smad2
Authors: Bao Yonghua , Chen Zhiguo , Guo Yongchen , Zhao Tiesuo , Feng Yansheng , Jiao Yunjuan , Li Zexin , Wang Jianguo , Zhao Weixing , Li Kai , Wang Qian , Wang Jiaqi , Zhang Huijuan , Yang Wancai , Yang Wancai 
Published: May 2015

Abstract
Colorectal cancer is one of the most common malignant diseases worldwide, but the causes of colorectal carcinogenesis are largely unknown. Using a miRNA array we have identified differential expression of some microRNAs in colorectal cancer and adjacent normal mucosa. Most of these miRNAs have been validated in colorectal tissues by quantitative RT-PCR. One of the most changed miRNAs is miR-27a. The level of miR-27 was significantly reduced in colon cancers in compared with matched normal mucosa, the reduced expression of miR-27a was also associated with colorectal cancer pathological stages - miR-27a was more reduced at stages III/IV, compared to stage II. The levels of miR-27a in human colon cancer cell lines were also less than that in human normal colon epithelial cell lines. Using bioinformatic and systemic analysis, two targets of miR-27a were predicted, they were SPGG1 and Smad2. The expression levels of SPGG1 and Smad2 were negatively correlated with miR-27a. Dual luciferase assay showed that overexpression of miR-27 significantly repressed SPGG1 and Smad2 transcriptional activities. Increasing miR-27 expression also inhibited SPGG1 and Smad2 protein levels in colon cancer cells. Functional studies revealed that overexpression of miR-27 inhibited colon cancer cell proliferation, promoted apoptosis and attenuated cell migration, which were linked to downregulation of p-STAT3 and upregulation of phosphorylated JNK1. Taken together, our results demonstrated that the expression levels of miR-27a were lower in colorectal cancer tissues in comparison to the non-tumor tissues and was related to pathological stages, suggesting that down-regulation of this miRNA could contribute to colorectal tumorigenesis and the acquisition of a more aggressive phenotype in colorectal cancer, which could be through targeting SPGG1 and Smad2.
Note: This abstract was not presented at the meeting.
Citation Format: Yonghua Bao, Zhiguo Chen, Yongchen Guo, Tiesuo Zhao, Yansheng Feng, Yunjuan Jiao, Zexin Li, Jianguo Wang, Weixing Zhao, Kai Li, Qian Wang, Jiaqi Wang, Huijuan Zhang, Wancai Yang, Wancai Yang. MicorRNA-27a functions as a tumor suppressor in colorectal cancer through targeting SPGG1 and Smad2. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5244. doi:10.1158/1538-7445.AM2014-5244
Abstract 5247: Comprehensive and systematic identification of miR-215 targets in colon cancer via a novel translation capture immunoprecipitation (TrIP) approach
Authors: Fesler Andrew , Xu Xiao , Chen Emily , Ju Jingfang 
Published: May 2015

Abstract
The important roles that non-coding miRNAs play in cancer development, makes the investigation of the various genes they target particularly crucial. In addition to targeting mRNA transcripts for degradation, miRNA can also alter gene expression at the translational level to achieve rapid regulation. It has been a technical challenge to study translational control using a small number of cells. We have overcome this hurdle by developing a translational capture immunoprecipitation approach (TrIP) to investigate RNA binding proteins or non-coding RNA regulation at the translational level from a small numbers of cells. The new approach is based on the fact that nascent translated polypeptides are associated with hsp70 chaperones along with actively translating mRNA transcript complexes, called polyribosomes. We are able to isolate actively translating mRNA from free cytoplasmic mRNA by immunoprecipitation of hsp70 associated polyribosome complexes. In this study, we utilize this novel approach to identify both degraded and non-degraded mRNA transcripts targeted by miR-215 in colon cancer. Following miR-215 overexpression in colon cancer cells, actively translating mRNA transcripts were isolated using the TrIP technique and purified following standard RNA isolation techniques. We were able to identify additional non-degraded mRNA targets regulated by miR-215 using a TrIP with transcriptome-wide microarray based approach, when compared to a generic approach based on steady state total RNA that can only identify degraded targets. Specific targets were independently validated using qRT-PCR analysis. We further validated miR-215 targets at the protein level with a comprehensive and high-throughput quantitative SILAC proteomics analysis. Protein targets were further validated using Western blotting with select positive control targets including TYMS, DTL and DHFR. This approach offers the unique opportunity to understand not only the mRNA targets a miRNA may target for degradation, but also those it regulates at the translational level, providing unique insight into the actions of miRNAs. Interest in this type of thorough analysis of different miRNAs or RNA binding proteins will likely continue to grow as the important roles miRNA play in cancer are further investigated.
Citation Format: Andrew Fesler, Xiao Xu, Emily Chen, Jingfang Ju. Comprehensive and systematic identification of miR-215 targets in colon cancer via a novel translation capture immunoprecipitation (TrIP) approach. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5247. doi:10.1158/1538-7445.AM2014-5247
Abstract 526: Overexpression of chromosome 3q26-29 miRNAs in squamous cell carcinoma of the lung
Authors: Qian Jun , Ji Xiangming , Zou Yong , Hoeksema Megan , Chen Heidi , Massion Pierre P. 
Published: May 2015

Abstract
The amplification of the distal portion of chromosome 3q in lung cancer is a major signature of neoplastic transformation, particularly in the squamous cell carcinoma (SCC) of the lung. A number of potential drivers in the 3q amplicon have been identified and are proposed to contribute to the development of lung SCC. miRNAs have emerged as a new class of small, non-coding RNAs that regulate gene expression and might act as integral parts of the molecular architecture of oncogene and tumor suppressor networks in human cancer, including non-small cell lung cancer (NSCLC). miR 1224-5p, 1248 and 944 are located at 3q amplicon and overexpressed in 50%, 26% and 53% of 30 primary SCCs when compared to normal tissues. The overexpression of these miRNAs was further validated in 237 TCGA lung SCC samples compared with 35 normal tissues (p=0.007, 1.18E-16 and 7.71E-20, respectively). The expression of the three miRNAs was higher in lung SCC compared to lung adenocarcinomas (p=8.19E-05, 1.04E-33 and 3.37E-95, respectively), suggesting unique roles of these miRNAs in the lung SCC development. Using miRNA mRNA target prediction tools (miRANDA and TargetScan) and in the combination with a literature search, we found RUNX1T1 and SMAD4 were candidate tumor suppressor gene target for miRNA-1224-5p and miRNA-1248. Downregulation of RUNX1T1 and SMAD4 were confirmed in TCGA lung SCC dataset. Using real-time RT-PCR, we found that the same three miRNAs 1224-5p, 1248 and 944 are overexpressed in 3q amplified lung SCC cell lines H520 and HCC95. When miRNA inhibitors were used to repress the expression of miR-1224-5p or miR-1248 in H520, we found that RUNX1T1 and SMAD4 protein expression levels were increased, suggesting that these tumor suppressor genes are regulated by miR-1224-5p or miR-1248. Lastly, knockdown of miR-1224-5p or miR-1248 using miRNA inhibitors led to 35-60% growth inhibition in H520 and HCC95 cells. Together, these results indicate potential roles for miR-1245-5p and 1248 in regulating cell proliferation by directly targeting tumor suppressor genes RUNX1T1 or SMAD4 in lung SCC. This work provides, for the first time, evidence for overexpression of miRNAs at the 3q26-29 amplicon that might be implicated in the oncogenesis of lung SCC. The work is supported by the NIH Grant R01 CA102353 to PPM and Lung Cancer Research Foundation grant (2011) to JQ.
Note: This abstract was not presented at the meeting.
Citation Format: Jun Qian, Xiangming Ji, Yong Zou, Megan Hoeksema, Heidi Chen, Pierre P. Massion. Overexpression of chromosome 3q26-29 miRNAs in squamous cell carcinoma of the lung. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 526. doi:10.1158/1538-7445.AM2014-526
Abstract 5269: Impact of K-ras status on differential expression of TIMP-1 in lung adenocarcinoma
Authors: Kutiyanawalla Ammar , Gupta-Ghoshal Sampa , Lee Byung Rho , Kolhe Ravindra , Rojiani Amyn M. , Rojiani Mumtaz V. 
Published: May 2015

Abstract
Tissue inhibitor of metalloproteinase-1 exhibits a range of novel functions in addition to its initially recognized activity as a physiological inhibitor of MMPs. Two specific activities have been of significant interest in the context of oncology - inhibition of apoptosis and induction of cell proliferation. Previously we have shown that over-expressing TIMP-1 in a lung adenocarcinoma cell line H2009 results in more aggressive and larger tumors in vivo with increased invasion and colony formation in vitro. Subsequently we demonstrated elevated levels of Bcl-2 with a concomitant reduction in apoptosis induced by staurosporine. In the present study, we have sought to define a relationship between TIMP-1 expression levels in non-small-cell-lung-carcinoma (NSCLC) cell lines in relation to K-ras mutation. We identified a differential expression pattern of TIMP-1 in various NSCLC cell lines and also found that TIMP-1 overexpressing cell lines also had higher levels of Bcl-2 and vice versa. Upon further analysis, we were able to correlate a low TIMP-1 expression with K-ras dependence and high levels of E-cadherin expression as in H2009 and H441. Similarly, K-ras independent cell line A549, expressed low levels of E-cadherin and elevated TIMP-1. E-cadherin distribution was confirmed in A549 and H2009 cells by immunofluorescence. Since N-cadherin cleavage has been shown to be inhibited by TIMP-1, we examined N-cadherin levels by western blot. Results indicate that A549 exhibiting high levels of TIMP-1 had increased levels of N-cadherin whereas the low TIMP-1 expressing cell lines had lower N-cadherin levels. A spheroid formation assay to determine the aggressiveness of cell lines revealed that K-ras dependent cell line formed spheroids that were smaller and less migratory than K-ras independent cell line whereas the K-ras independent cell line A549 formed spheroids that were larger, more spread out exhibiting wider migratory properties. The present study underscores the multiple biologic properties of TIMP-1. It provides further mechanistic understanding of its documented role as a prognostic marker and a potential therapeutic target in various malignancies, particularly lung carcinoma. This study was supported in part by a Distinguished Cancer Scientist Award to AMR from the Georgia Research Alliance.
Citation Format: Ammar Kutiyanawalla, Sampa Gupta-Ghoshal, Byung Rho Lee, Ravindra Kolhe, Amyn M. Rojiani, Mumtaz V. Rojiani. Impact of K-ras status on differential expression of TIMP-1 in lung adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5269. doi:10.1158/1538-7445.AM2014-5269
Abstract 5270: Prevalence of inactivating protein kinase C mutations in human cancers
Authors: Antal Corina E. , Kang Emily , Stephenson Natalie L. , Trotter Eleanor W. , Hunter Tony , Brognard John , Newton Alexandra 
Published: May 2015

Abstract
Protein kinase C (PKC) levels are aberrant in diverse cancers and over 400 mutations in PKC have been identified in human cancers. Here we characterized PKC mutations identified in human cancers to investigate whether PKCs function as oncogenes or tumor suppressors or whether their function is isozyme and/or context dependent. Live-cell imaging was used to determine how these mutations affect PKC translocation, subcellular localization, and activity. Cell-based assays were used to determine how PKC mutations alter proliferation, apoptosis, migration, and anchorage-independent growth. Of 37 mutations we examined thus far, 24 of them reduced or completely abolished PKC activity, while only 1 increased it. These mutations reside within the diacylglycerol-binding C1 domain, the Ca2+-binding C2 domain, or the kinase domain of conventional, novel, or atypical PKCs. The inactivating mutations ablate activity by either impeding Ca2+ or diacylglycerol binding, or by yielding a misfolded kinase. Our results suggest that PKC can act as a tumor suppressor in certain cancers. Understanding whether mutations are activating or inactivating in specific cancers would allow us to determine whether therapeutic strategies should target ways to inactivate or activate PKC in the respective cancers.
Citation Format: Corina E. Antal, Emily Kang, Natalie L. Stephenson, Eleanor W. Trotter, Tony Hunter, John Brognard, Alexandra Newton. Prevalence of inactivating protein kinase C mutations in human cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5270. doi:10.1158/1538-7445.AM2014-5270
Abstract 5273: VBIM technology identifies beta-catenin-like protein (BCLP) as a novel negative regulator of NF-kB
Authors: Mundade Rasika , Lu Tao 
Published: May 2015

Abstract
Colon cancer is the second leading cause of cancer related deaths in the United States. The nuclear factor kB (NF-kB) is an important family of transcription factors whose aberrant activation has been found in many types of cancer, including colon cancer. Therefore, understanding the regulation of NF-kB is of ultimate importance for cancer therapy. The purpose of this study is to use a novel validation-based insertional mutagenesis (VBIM) strategy to identify novel regulators of NF-kB, and further evaluate their roles in the regulation of NF-kB signaling in colon cancer cells. We infected D1 cells (293 derived cells with hyper active NF-kB activity) with VBIM virus to cause the overexpression of negative regulators of NF-kB, and then further selected the mutant cells with low NF-kB activity under ganciclovir (GCV) treatment. Targeted gene was then identified by using VBIM specific primers. In a preliminary screen, we identified the novel beta-catenin like protein (BCLP) gene as a negative regulator of NF-kB. Overexpression of BCLP led to decreased NF-kB activity by kB reporter assay, while knocking it down had the opposite effect. Furthermore, we found that overexpression of BCLP in HT29 colon cancer cells greatly reduced both the number and the size of colonies that were formed in a soft agar assay, while sh-RNA mediated knockdown resulted in an opposite effect, confirming that BCLP is a tumor suppressor in HT29 cells. Our future experiments aim to further assess the role of BCLP in colon tumor formation in a mouse xenograft model. In summary, by using the novel VBIM technique, we identified BCLP as a novel negative regulator of NF-kB. This discovery could lead to the establishment of BCLP as a potential biomarker and therapeutic target in colon cancer.
Citation Format: Rasika Mundade, Tao Lu. VBIM technology identifies beta-catenin-like protein (BCLP) as a novel negative regulator of NF-kB. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5273. doi:10.1158/1538-7445.AM2014-5273
Abstract 5278: Superoxide mediated selective tyrosine nitration of protein phosphatase 2A-B56δ stabilizes Bcl-2 phosphorylation and its anti-apoptotic activity
Authors: Low Ivan C. C. , Loh Thomas , Virshup David , Pervaiz Shazib 
Published: May 2015

Abstract
Our work over the years has provided strong evidence that an increase in intracellular superoxide anion provides cancer cells with a survival advantage and promotes tumor chemoresistance. The mechanisms underlying superoxide-mediated pro-survival signaling are poorly understood. Here we report that an increase in intracellular superoxide stabilizes the anti-apoptotic activity of Bcl-2 by mechanisms that involve sustained phosphorylation of Bcl-2 at serine 70. Of note, this effect on Bcl-2 S70 phosphorylation is a function of redox-dependent inactivation of Protein Phosphatase 2A (PP2A), which is targeted to Bcl-2 via its B56 subunit; superoxide induces the release of PP2A-AC catalytic core from Bcl-2-bound B56δ, resulting in sustained phosphorylation of Bcl-2 at S70. Dissociation of the PP2A heterotrimer results from the selective nitration (by peroxynitrite derived from the reaction of superoxide with NO) of a conserved tyrosine residue, which we identify as Y289 of B56δ (B56 δY289). Inhibition of B56δY289 nitration blocked the pro-survival effects of superoxide. Furthermore, we provide evidence for clinical relevance of these findings using primary tissue derived from human lymphoma biopsies. Taken together, these data provide evidence for a novel mechanism in which an increase in intracellular superoxide regulates PP2A function via specific B56 subunit tyrosine nitration, and that PP2A-B56 nitration may be a general mechanism for redox-regulated cellular signaling.
Citation Format: Ivan C. C. Low, Thomas Loh, David Virshup, Shazib Pervaiz. Superoxide mediated selective tyrosine nitration of protein phosphatase 2A-B56δ stabilizes Bcl-2 phosphorylation and its anti-apoptotic activity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5278. doi:10.1158/1538-7445.AM2014-5278