bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4973: Recurrent chimeric RNAs enriched in human prostate cancer identified by deep-sequencing
Authors: Kannan Kalpana , Wang Liguo , Wang Jianghua , Ittmann Michael , Li Wei , Yen Laising 
Published: June 2012

Abstract
Chimeric transcripts unrelated to chromosomal rearrangement are primarily generated by two transcription-induced mechanisms: read-through/splicing and trans-splicing. Both mechanisms result in fused transcripts that possess sequences from both genes. Although the exact cause and regulation of chimeric transcripts are unknown, chimeric RNAs, like fusion genes, are expected to increase the proteomic diversity in cells through chimeric proteins or altered regulation of participating mRNAs. Despite its importance, few studies have reported on chimeric RNAs, especially regarding their presence and roles in human cancers. In this study, we took advantage of the analytical power of paired-end high throughput sequencing to characterize chimeric transcripts enriched in human prostate cancer. By deep-sequencing the transcribed mRNA (transcriptome) of 20 clinical prostate cancer tissues, in addition to 10 matched benign prostate tissues from the same patients, we obtained greater than 500 million useful sequence reads. This strategy combined with stringent bioinformatic criteria enabled the identification of 27 novel and highly recurrent chimeric RNAs that have never been described before. The novel chimeric transcripts were experimentally validated to be present in human prostate cancer samples in a recurrent manner. Further experimental analysis identify several chimeric transcripts are present in the human prostate cancer cell lines, but not in primary human prostate epithelium cells, implying their associations with cancer mechanisms. Importantly, one of these chimeras appeared to be highly cancer-enriched, as it is confirmed to be expressed at significantly higher levels in human prostate cancers but present at very low levels in non-cancer prostates. Our results suggest that chimeric RNAs are more abundant than previously estimated. The RNA fusion junctions of these novel recurrent chimeras, as determined experimentally, suggest that many of them would generate altered or aberrant protein sequences, potentially leading to abnormal functions in cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4973. doi:10.1158/1538-7445.AM2011-4973
Abstract 498: MicroRNA200c attenuated metastatic abilities in head and neck squamous cell carcinoma-derived cancer cells
Authors: Chiou Shih-Hwa , Chen Kuan-Hsuan , Lo Wen-Liang , Chen Yi-Wei , Chen Yu-Chih 
Published: June 2012

Abstract
MicroRNA-200c (miR200c) is emerging as an important regulator of epithelial-mesenchymal transition (EMT), tumorigenicity and cancer metastasis. Recent investigation showed miR200c can regulate the stemness in breast cancer stem cell through directly binding the 3’UTR of Bmi1. However, the role of miR200c in head and neck squamous cell carcinoma (HNSCC) and HNSCC-associated CSC has never been determined. In this study, we first demonstrated that miR200c expression was significantly decreased but Bmi1 expression was increased in HNSCC tissues as compared to adjacent normal cells. Secondly, HNSCC-ALDH1+CD44+ cells presented tumor initiating and radioresistant properties with high EMT. Consistently, the Bmi1 expression was significantly up-regulated and miR200c was down-regulated in HNSCC-ALDH1+CD44+ compared to other isolated subsets of HNSCC cells. Furthermore, miR-200c overexpression or Bmi1 knockdown through lentiviral infection could significantly inhibit the clonogenic and invasive abilities of HNSCC-ALDH1+CD44+ cells. Moreover, overexpression of Bmi-1 promoted HNSCC-ALDH1−CD44− to acquire CSC properties which are similar to HNSCC-ALDH1+CD44+. In contrast, overexpressing of miR200c shifted transcriptomes profiles of ALDH1+CD44+ similar to those of ALDH1-/CD44- populations and abolished self-renewal as well as EMT properties in ALDH1+CD44+. Most importantly, overexpression of miR-200c in ALDH1+CD44+ or ALDH1−CD44−Bmi-1over cells effectively blocked tumor growth and lung metastasis, and significantly prolonged survival time in neck orthotropic-transplanted immunocompromised mice. Lastly, miR200c is significantly reduced in high grade, metastatic HNSCC tissues compared to low-grade HNSCC tissues. In sum, these results show that miR200c negatively modulates Bmi1 expression and plays a role as a tumor suppressor in HNSCC through eliminating HNSCC-CSC population. Restoration of miR200c in HNSCC and CSC may pave a new approach for therapeutic treatment in the future.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 498. doi:10.1158/1538-7445.AM2011-498
Abstract 4983: Integrative analysis of DNA copy number and gene expression identifies G3BP1 and HIRA as potential therapeutic targets against metastatic oral squamous cell carcinoma
Authors: Xu Chang , Liu Yan , Wang Pei , Fan Wenhong , Upton Melissa P. , Houck John R. , Lohavanichbutr Pawadee , Doody David R. , Futran Neal D. , Zhao Lue Ping , Schwartz Stephen M. , Chen Chu , Méndez Eduardo 
Published: June 2012

Abstract
The presence of lymph node metastasis is associated with a 50% reduction of 5-year survival in patients with oral squamous cell carcinoma (OSCC). We set out to combine DNA copy number aberrations (CNAs) with gene expression profiles, to identify CNAs-associated genes dysregulated in metastatic OSCC, and determine whether these genes can be targeted to selectively kill metastatic OSCC tumor cells. Toward this end, we interrogated DNA and RNA of the same OSCC cell populations laser micro-dissected from non-metastatic primary tumors (n=17) and metastatic lymph nodes (n=20) using Affymetrix 250K Nsp single-nucleotide polymorphism (SNP) arrays and U133 Plus 2.0 arrays, respectively. With a false discovery rate (FDR) &lt; 5%, 1988 transcripts were found to be differentially expressed between primary and metastatic OSCC. Out of these, 114 transcripts showed significant correlation between their DNA copy number alternations (estimated using SNPs within 250 kb upstream and downstream of the transcript) and gene expression (FDR &lt; 0.01). Among these CNA-correlated transcripts, 95 had significantly different DNA copy numbers between metastatic and non-metastatic OSCC (FDR &lt;0.01 by Wilcoxon rank test). These 95 transcripts (representing 87 genes) mainly clustered around three genomic locations: 3p25.3-22.1, 9p24.1- 22.3 and 18q21.1-22.3. Among these 87 genes, we selected 28 of the 58 genes that were over-amplified and over-expressed in metastatic OSCC and conducted a high-throughput siRNA-mediated gene knockdown screen in five cell lines derived from primary and lymph node metastatic OSCC. The expression-knockdown of 18 genes showed 30% or more growth suppression in at least one cell line as compared to mock controls in which the cells were treated with transfection reagent only without the siRNA (P &lt; 0.01). In particular, knocking-down G3BP1 and HIRA selectively suppressed the growth of all OSCC cell lines derived from lymph node metastases when compared to non-metastatic lines. Further investigation is warranted to confirm these findings and to examine the biological role of G3BP1 and HIRA in OSCC metastasis and their potential as therapeutic targets.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4983. doi:10.1158/1538-7445.AM2011-4983
Abstract 4991: Upregulation and the role of IKBKE in non-small cell lung cancer
Authors: Kim Donghwa , Guo Jianping , Gao Jingchun , Shu Shaokun , Haura Eric B. , Cheng Jin Q. 
Published: June 2012

Abstract
IKBKE is a serine/threonine protein kinase that belongs to the IKK kinase family. Recent studies have shown IKBKE as a breast and ovary cancer oncogene. Here we evaluated IKBKE expression and kinase activity in 30 NSCLC cell lines and 176 primary NSCLC specimens including 38 tumor/normal lung tissue pairs. Elevated protein levels of IKBKE were detected in 16 (52.6%) cell lines and 91 (51.7%) primary tumors. The mRNA levels and kinase activity of IKBKE are consistent with its protein status, suggesting that post-transcriptional regulation is not involved in increase IKBKE protein expression and that the IKBKE activation largely depends on its protein levels in NSCLCs. In addition, ectopic expression of IKBKE decreases and depletion of IKBKE increases the apoptosis induced by chemotherapeutic agents. Moreover, IKBKE is considerably induced by tobacco-derived carcinogens NNK and nicotine through Stat3 pathway. These findings demonstrated for the first time that deregulation of IKBKE is a recurrent event in NSCLC and could play a pivotal role in NSCLC development, and thus IKBKE is a critical therapeutic target in this malignancy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4991. doi:10.1158/1538-7445.AM2011-4991
Abstract 4994: Downstream targets of Id1 transcription factor in non-small cell lung cancer
Authors: Nair Sajitha G. , Chellappan Srikumar 
Published: June 2012

Abstract
Id1 (Inhibitor of DNA binding/Differentiation) is a helix loop helix (HLH) protein, regulates transcription by binding to bHLH transcription factors and preventing their binding to the DNA. Id1 is especially known to mediate repression of E box proteins and Ets transcription factors. Id1 gene is overexpressed in lung, breast, pancreatic and prostate cancer and it is thought to promote the progression and metastasis of these tumors. At the same time, not much is known about its role in non-small cell lung carcinoma.Preliminary studies from our lab shows that Nicotine as well as EGF induces Id1 in both adenocarcinoma and squamous carcinoma cells and is notably upregulated in metastatic lung cancers. Depletion of Id1 also prevents the proliferation and invasion of NSCLS cells. Attempts were made to understand the downstream effectors of Id1 function in lung cancer progression and metastasis. As a step in this direction, A549 (K-Ras mutant, EGFR wild-type) and H1650 (K-Ras wild-type, EGFR mutant) cells were transfected with short interfering RNA (siRNA) for Id1and stimulated with 1μm Nicotine or 100ng/ml EGF. The samples were subjected to microarray analysis to identify various genes upregulated and downregulated in the Id1 siRNA transfected cell lines. 200 genes were upregulated 2 fold or more by Nicotine and 150 by EGF. Few genes such as stathmin like-3 (STMN3), GSPT1 (G1 to S phase transition), TPD52 (tumor protein D52) were downregulated in the absence of Id1 suggesting those are Id1 regulated genes. The microarray results were validated using Real-time PCR for the above genes. Further depletion of these three genes resulted in decreased cell proliferation, migration and invasion. Indeed STMN3 promoter could be induced by Id1 and Id1 was necessary for Nicotine to induce this gene. These results might reveal the mechanisms by which Id1 promotes tumor progression and metastasis. STMN3 is a microtubule destabilizing phosphoprotein which is overexpressed in adenocarcinoma as well as squamous cell carcinoma and induced tumor cell proliferation, migration and matrix invasion in respective cell lines. GSPT1, which is also known as eukaryotic translation release factor eRF3 and TPD52 are also reported to be over expressed in various kinds of cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4994. doi:10.1158/1538-7445.AM2011-4994
Abstract 4997: The isolation of miRNA targeting EGFR gene in lung cancer
Authors: Yamaguchi Gaku , Ikeda Norihiko , Kuroda Masahiko , Ohira Tatsuo , Uchida Osamu , Kajiwara Naohiro , Usuda Jitsuo , Kakihana Masatoshi , Saji Hisashi , Takanashi Masakatsu , Fujita Kohji , Yoshida Kohichi , Kataba Hiroaki , Iwasaki Kentaro , Tanaka Masami 
Published: June 2012

Abstract
MicroRNAs (miRNAs) belong to a class of the endogenously expressed non-coding small RNAs which primarily function as gene regulators. Growing evidence suggests that microRNAs have a significant role in tumor development.
Lung cancer, predominantly non-small cell lung cancer (NSCLC), remains the leading cause of cancer related deaths worldwide. Although EGFR signaling is important and well studied with respect to NSCLC progression, little is known about how miRNAs mediate EGFR signaling to modulate tumorigenesis.
In this study, we identified miRNAs that directly regulate the EGFR gene expression. We employed computational tools such as Pictar and Target Scan, and putative targets of 88 miRNAs were identified within the EGFR mRNA. Then, we analyzed the expression of EGFR in miRNAs-transfected human lung cancer cells (H3255, A549, Hcc827) by real time-PCR methods. In addition, we performed argonaute (AGO) IP experiments to ascertain whether these algorithmically predicted miRNA targets are biologically true targets in EGFR. Convincingly, we found that two miRNAs directly regulated the EGFR and both of these miRNAs also inhibited cell growth in cell viability assays. Identifying microRNA regulators of EGFR may contribute in development of novel therapeutics, and non-invasive early detection biomarkers for NSCLC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4997. doi:10.1158/1538-7445.AM2011-4997
Abstract 4999: FK506 binding protein 51 (FKBP51) sustains stemness and the metastatic potential of malignant melanoma
Authors: Romano Simona , Sorrentino Antonio , Pace AnnaLaura Di , Staibano Stefania , Mascolo Massimo , Bisogni Rita , Ilardi Gennaro , Romano Maria Fiammetta 
Published: June 2012

Abstract
Background. FKBP51 is a cochaperone with peptidyl-prolyl isomerase activity that regulates several biological processes in the cell, through protein-protein interaction. There is increasing evidence that FKBP51 hyperexpression is associated with cancer and this protein has a relevant role in sustaining cell growth, malignancy, and resistance to therapy. Very recently, we have found that FKBP51 is a protein associated with malignant melanoma. Its expression correlates with tumor aggressiveness and is maximal in metastatic lesions. Moreover, we have found that melanoma cancer stem cells express FKBP51 at levels higher than the other tumor cells and observed a 4 to 40 fold increase in the number of cancer stem cells, in cultures of melanoma cells stably transfected with FKBP51. Mitotic index, stemness features and angiogenesis are the main signs of aggressive melanoma. To better understand the role of FKBP51 in the biology and progression of melanoma, we attempted to investigate if this protein regulated the expression of molecules associated with tumor progression, namely the Chromatin Assembly Factor-1 (CAF-1) p60; the ATP-Binding Cassette family members ABCG2 and ABCB5; and the pro-angiogenic factor, endoglin or TβRIII. Methods. The melanoma cell line SAN was used for these experiments. FKBP51 knock down was obtained with siRNA, FKBP51 hyperexpression was obtained by stably transfecting SAN with a vector containing the FKBP51 human gene under a CMV promoter. Protein expression was measured by western blot and flow cytometry; mRNA was quantified by Realtime PCR. Results. We found that ABCG2 and CAF1 p60 mRNA levels were reduced by 5 and 2.5 folds, respectively, in FKBP51-silenced cells, in comparison with non-silenced cells. Reduced ABCB5 and CAF-1 p60 protein levels were detected by Western blot. By contrast, a clear increase of ABCB5 and CAF-1 p60 protein levels was observed in FKBP51 hyperexpressing cells. Flow cytometry showed that 39% of melanoma cells expressed endoglin. Such percentage was decreased to 5% by FKBP51 silencing, whereas it increased up to 78% in FKBP51 hyperexpressing cells. Finally, we found that CAF-1 and endoglin were co-expressed in more than 80% of ABCG2+ cells, whereas their expression was &lt;40% in ABCG2- cells. Conclusions. FKBP51 regulates molecules involved in chromatin rearrangement, stemness and metastatization of malignant melanoma suggesting that this cochaperone may act as a transcriptional coactivator of oncogenes in melanoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4999. doi:10.1158/1538-7445.AM2011-4999
Abstract 5: Synthesis and biological evaluation of 5, 5’ substituted apogossypol and apogossypolone derivatives as pan-active inhibitors of anti-apoptotic B-cell lymphoma/leukemia-2 (Bcl-2) family proteins
Authors: Wei Jun , Placzek William J. , Stebbins John L. , Reed John C. , Pellecchia Maurizio , Fisher Paul B. , Dash Rupesh , Jamieson Catriona , Kitada Shinichi 
Published: June 2012

Abstract
Overexpression of anti-apoptotic Bcl-2 family proteins is commonly related with tumor maintenance, progression, and chemoresistance. Inhibition of these anti-apoptotic proteins is an attractive approach for cancer therapy. Guided by nuclear magnetic resonance (NMR) binding assays and computational docking studies, a series of 5, 5’ substituted Apogossypol and Apogossypolone derivatives was synthesized and identified pan-active antagonists of anti-apoptotic Bcl-2 family proteins, with binding potency in the low micromolar to nanomolar range. Apogossypol derivative BI97C1 inhibits the binding of BH3 peptides to Bcl-XL, Bcl-2 and Mcl-1 with IC50 values of 0.31, 0.32 and 0.20 µM, respectively. In a cellular assay, BI97C1 potently inhibits cell growth in the H460 human lung cancer and PC-3 human prostate cancer cell lines with EC50 values of 0.40 and 0.13 µM, respectively, and effectively induces apoptosis of the BP3 human lymphoma cell line (EC50 = 0.049 µM) in a dose-dependent manner. Apogossypolone derivative BI97D1 also potently inhibit cell growth in many cancer cell lines. BI97C1 and BI97D1 further display in vivo efficacy in transgenic mice in which Bcl-2 is overexpressed in splenic B-cells and also demonstrated superior single-agent antitumor efficacy in mouse xenograft model and represent promising drug leads for the development of novel apoptosis-based therapies for cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5. doi:10.1158/1538-7445.AM2011-5
Abstract 5003: β-catenin regulates multiple oncogenes in glioma
Authors: Yue Xiao , Han Lei , Lan Fengming , Yang Yang , Shi Zhendong , Zou Jian , Pu Peiyu , Kang Chunsheng 
Published: June 2012

Abstract
Gliomas are the most common primary intracranial tumors. Understanding the molecular basis of gliomas progression is required to develop more effective therapies. Although, disregulated of Wnt/β-catenin pathway is a hallmark of many cancers, little is known about its role in human gliomas. The expression of components of Wnt pathway in 80 astrocytic glioma specimens with different grades was examined by immunohistochemistry. The protein expression levels of Wnt1, Wnt2, β-catenin and Cyclin D1 were positively correlated with World Health Organization (WHO) grades of gliomas. To explore whether β-catenin can serve as a therapeutic target for glioma, we knockdowned β-catenin expression by siRNA and found that apoptosis was induced, cell proliferation and invasive ability were inhibited in vitro in U87, LN229 and A172 cells; xenograft tumors from β-catenin siRNA-treated LN229 cells were suppressed in vivo. To investigate the underlying mechanisms, we extracted gene/protein interactions by text mining Pubmed abstracts. Screening Pubmed by natural language processing, we identified 543 genes that interacted with β-catenin. Integrating multiple data sources through the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), we created the β-catenin related genes knowledge-driven network, identifying and interactions of this network with EGFR pathway. In both in vitro and in vivo studies, our results confirmed down-regulation of β-catenin induced reduced expression of EGFR, STAT3 and AKT1 mRNA and protein, besides, the level of phosphorylated Akt also decreased. A similar reduction in expression of CyclinD1, MMP2 and MMP9, downstream genes of the EGFR pathway, was observed. We examined the promoter region of EGFR and STAT3 gene for regulating DNA-binding elements and revealed the presence of putative β-catenin/TCF-4-binding sites. Further, EGFR and STAT3 were identified as direct targets of the Wnt/β-catenin pathway in glioma cells by ChIP and luciferase reporter assay. Taken together, we demonstrate that Wnt/β-catenin pathway is overexpressed in glioma and correlats closely with the progression of gliomas and EGFR and STAT3 are regulated by β-catenin/TCF-4 at the transcriptional level and interruption of β-catenin supresses the EGFR pathway by blocking multiple oncogenic targets in human glioma cells. Wnt/β-catenin pathway is of critical importance in the gliomagenesis and intervention of this pathway may provide a new therapeutic approach for malignant gliomas.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5003. doi:10.1158/1538-7445.AM2011-5003