bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3994: Loss of miR-23b enhances Pyk2-induced glioma cell migration and invasion
Authors: Paquette Kimberly M. , Ross Julianna TD , Kloss Jean , Nasser Sara , Yang Zhongbo , Paulino Vincent M. , Kim Seungchan , Loftus Joseph C. , Tran Nhan L. 
Published: June 2012

Abstract
Glioblastoma is the most common and lethal type of primary brain tumor. Despite recent therapeutic advances in other cancers, the treatment of glioblastomas remains ineffective and essentially palliative due the highly invasive nature of the disease. To discern molecular mechanisms that drive GBM migration, we investigated the potential role of differential expression of microRNAs (miRNA) by comparing the matched large-scale, genome-wide miRNA expression profiles of migrating and migration-restricted human glioma cells. Using a radial migration assay, migrating and non-migrating populations from seven well-established glioma cell lines were isolated and utilized for miRNA expression analysis. Statistical analyses revealed 22 miRNAs common to all seven glioma cell lines were down-regulated in the migrating cell population (p &lt; 0.0005) relative to cells in the non-migratory population. Specifically, we report here that the expression level of miR-23b was markedly down-regulated in migrating glioma cells as compared to migration-restricted cells. Over-expression of miR-23b significantly inhibited glioma cell migration and invasion. A bioinformatics search revealed a conserved target site within the 3’untranslated region (UTR) of Pyk2, a non-receptor tyrosine kinase that has been previously implicated in the regulation of glioma cell migration and invasion. Increased expression of miR-23b reduced the expression level of Pyk2 in glioma cells indicating that miR-23b targets Pyk2. Notably, increased expression of miR-23b did not alter the expression level of the related focal adhesion kinase FAK indicating that miR-23b specifically inhibits the expression Pyk2. Taken together, our study demonstrates that reduced expression of miR-23b facilitates the enhancement of glioma cell migration and invasion via modulation of Pyk2 expression. Thus, these data suggest that certain miRNAs may regulate glioma migration and invasion to influence the progression of this disease.
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 3994. doi:10.1158/1538-7445.AM2011-3994
Abstract 3995: Identification of putative miRNA targets by a systems biological approach in NCI-60 data
Authors: Kim Sangbae , Park Yun-Yong , Park Eun-Sung , Oh Sang-Cheol , Kim Jong-Seung , Sohn Bo-Hwa , Kim Soo-Mi , Davis Michael A. , Mills Gordon B. , Lee Ju-Seog 
Published: June 2012

Abstract
MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules and on average only 22 nucleotides long that regulate gene expression at the post-transcriptional level. Target predictions of miRNA based on sequence are limited due to too many candidates resulting in high false positives. To overcome this limitation functional target prediction approaches have been investigated by using mRNA and miRNA expression data. These approaches used in the computational assessment of functional miRNA-target association. However, these approaches with miRNA-mRNA association were not enough to verify real functional targets at protein level, which could affect on biological signaling pathway. Therefore, in order to overcome current limitation we developed a novel correlation-based approach (sequence-independence) that predict the association of miRNAs with signaling pathways by using genomics and proteomics data from NCI-60 cancer cell lines (mRNA, miRNA, and protein expression data). To identify miRNA-protein association, we used two correlation-based methods: direct comparison (miRNA-protein pairs) and indirect comparison (miRNA-mRNA and protein-mRNA pairs), then compared their outputs. In direct comparison, we calculated Pearson correlation coefficients for 96k probe pairs and found over 3 k significant correlated pairs (3.2 %) at the cut-off p-value &lt; 0.005: among them 53.4 % were negative and 46.6% were positive. In indirect comparison, we ranked the number of correlated mRNA probes between miRNA-mRNA and protein-mRNA pairs, in which we calculated over 11 and 5.7 million probe pairs respectively. Then, two significant output pair sets were combined by intersection of mRNA probes and then determined the number of common probes. With these determined numbers, finally we generated association score matrix between miRNA and protein probes. Using those score matrix, we evaluated the highly associated miRNAs with 40 biological pathways, which play critical roles in cell cycle, proliferation and metastasis. In conclusion, we developed a noble expression profile-based approach to systematically predict potential miRNA functional targets which play critical roles in cell signaling pathways from the NCI-60 genomic and proteomic data at whole genomic scale.
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 3995. doi:10.1158/1538-7445.AM2011-3995
Abstract 3997: MiR-181 promotes megakaryocyte differentiation
Authors: Li Xiaobo , Gao Lin , Howell Paul , Owen Laurie , Xi Yaguang 
Published: June 2012

Abstract
MiRNAs have attracted attention due to their key regulatory functions in biological events such as proliferation, differentiation, apoptosis, and tumorigenesis. A few recent studies reported on the existence of a reciprocal regulatory loop between the family of let-7 miRNAs and an RNA-binding protein lin28, both of which play important roles during cell differentiation. Using bipotent K562 human leukemia cells and human CD34+ hematopoietic stem cells as research models, we demonstrate that let-7 and lin28 appear to exhibit inverse expression trends in phorbol ester-induced megakaryocyte differentiation, while miR-181 is up-regulated early during this process. Enforced expression of miR-181a in K562 cells effectively represses lin28 expression, breaking up the lin28-let-7 reciprocal regulatory loop, and sequentially triggers megakaryocyte differentiation as measured by CD41 and CD61 induction. Elevated miR-181 also significantly increases the number of megakaryocyte colonies in CD34+ hematopoietic stem cells. However, miR-181 expression levels only slightly change during hemin-induced erythrocyte differentiation. These results suggest that miR-181 can function as a “molecular switch” during hematopoietic lineage differentiation and can be a potential target for future miRNA-oriented therapeutics for human 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 3997. doi:10.1158/1538-7445.AM2011-3997
Abstract 4003: MicroRNA 99b down-regulation in lung cancer tissues leads to fibroblast growth factor receptor 3 up-expression and acceleration of proliferation
Authors: Woong Son Ji , Kwon Sun Jung , Choi Eugene , Na Moon Jun , Jeon Young June 
Published: June 2012

Abstract
Background: Dysregulation of miRNA expression has been identified in a number of cancers and an accumulating data indicate that some miRNAs can function as tumor suppressors or oncogenes and are important in cancer development. Deletion or loss of function of a tumor-suppressing miRNA results in overexpression of target oncogenes. Conversely, activation or overexpression of an oncogenic miRNA results in silencing of tumor-suppressing target genes. According to miRNA profiles on microarray, miR-99b was down-expressed in Korean lung cancer. FGFR-3 is predicted target of miR-99b through two public algorithms. FGFR-3 has been demonstrated to be involved in the RAS/RAF/MEK/MAPK pathway through activation of p90 ribosomal S6 kinase. It has been reported that FGFRs are frequently overexpressed in NSCLC cell lines, suggesting that an FGFR-dependent autocrine signaling pathway may operate in a subset of NSCLCs.
Material & method: We studied expression of miR-99b and FGFR-3 using quantitative reverse transcription PCR (qRT-PCR) in lung cancer tissue. To examine whether miR-99b could regulate FGFR-3 in lung cancer, we performed transient transfection of pre-miR-99b into lung cancer cell line, then we performed qRT-PCR and western blot in HCC1438, HCC95, and H522 cells for analysis of FGFR-3 expression. We hypothesized the miR-99b has a role of inhibitor cell growth in lung cancer. To test this hypothesis, we performed cell proliferation assay.
Results: miR-99b was down-regulated and FGFR-3 was up-regulated in lung cancer. Over-expression of miR-99b induced marked reduction of FGFR-3 mRNA levels and protein level in lung cancer cell line HCC1438, HCC95, and H522. The growth rate in miR-99b precursor treated cell was lower than in negative control of miR treated cell.
Conclusion: Abnormal down-regulation of miR-99b could lead to the over-expression of FGFR-3 in lung cancer. miR-99b may be a potent tumor suppressor and may be a potential candidate of therapeutic tool in lung 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 4003. doi:10.1158/1538-7445.AM2011-4003
Abstract 4015: Flavopiridol-induced upregulation of HtrA1 is associated with suppression of its negative transcriptional regulator WT-1 and with enhanced chemosensitivity
Authors: Ohta Tsuyoshi , Khurana Ashwani , Maguire Jacie , He Xiaoping , Chien Jeremy , Bible Keith , Shridhar Viji 
Published: June 2012

Abstract
We previously identified serine protease HtrA1 as a down-regulated gene in epithelial ovarian cancer (EOC) that modulates cisplatin-induced cytotoxicity. However, the mechanism by which HtrA1 sensitizes cells to cisplatin-induced cytotoxicity remained unknown. We have shown previously that the pan-cyclin dependent kinase inhibitor flavopiridol (FP) sensitizes cells to cisplatin-induced cytotoxicity; we hypothesized that flavopiridol might therefore modulate the expression of pro-apoptotic proteins. Microarray data indicated that while flavopiridol treatment alone or in combination with cisplatin up-regulated HtrA1 expression by 2-3 fold (providing a means to upregulate HtrA1 expression), treatment with cisplatin alone had no effect. Interestingly, in searching for underlying mechanisms, we noted that WT-1 transcription factor binding elements that is present in HtrA1 promoter is down-regulated by flavopiridol in our microarray studies. Immunoblot analysis revealed that WT-1 is highly expressed in HtrA1-deficient OV167, OV202, PE04 and Ovcar3 cells but not in HtrA1-expressing SKOV3, TOV21G and PE01 cells, suggesting WT-1 negatively regulates HtrA1 expression in EOC. Immunoblot analysis showed FP treatment resulted in down-regulation of WT-1 with a corresponding increase in HtrA1 protein levels in OV202 cells. Additionally, stable down-regulation of WT-1 by short hairpin RNA (shRNA) in OV202 cells increased HtrA1 expression. Conversely, enhanced expression of full length WT-1 isoform in SKOV3 cells downregulated HtrA1 expression. Reporter assay showed that FP treatment upregulated HtrA1 promoter activity in OV202 cells. Reporter assay and chromatin immunoprecipitation experiments showed that WT-1 is specifically recruited to the HtrA1 promoter. Moreover, downregulation of WT-1 expression in OV202 cells increased cisplatin-mediated cytotoxicity as determined by both 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and clonogenic assays – an effect reversed by enhanced expression of HtrA1. Collectively, our studies demonstrate a linkage between the effects of flavopiridol on HtrA1 and its regulatory transcription factor WT-1 that appears in part to explain why flavopiridol has chemosensitizing properties
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 4015. doi:10.1158/1538-7445.AM2011-4015
Abstract 4019: Identification of SOX4 transcriptional target genes in human lung cancer
Authors: Castillo Sandra D. , Medina Pedro P. , Mariani Niccolò , Sanchez-Cespedes Montse 
Published: June 2012

Abstract
The search for novel oncogenes is becoming increasingly important in cancer genetics because they are suitable targets for therapeutic intervention. Our current work lays in study the role of the SOX4 transcription factor in human lung carcinogenesis. The SOX4 gene belongs to a large family of transcription factors related by homology in their DNA-binding domain and is predominantly expressed during embryonic development in heart, central nervous system, lung and thymus. SOX4 has been proposed as a candidate oncogene in many types of cancer such as bladder, prostate, colon, urothelial, adenoid cystic carcinoma and lung because of its increased expression in those tumors. Previous studies in our lab uncovered SOX4 gene amplification and concomitant over-expression in a subset of lung primary tumors and cancer cell lines. Interestingly, SOX4 expression was significantly greater in the SCLC cell lines.
Little is known about the transcriptional targets and pathways orchestrated by SOX4 during lung carcinogenesis. To further investigate SOX4 contribution to lung carcinogenesis we developed an inducible short-hairpin system in the NCI-H522 lung cancer cell line, which is known to carry SOX4 gene amplification and over-expression, in order to abrogate SOX4 expression in an inducible manner. Then, we performed an expression analysis using the Whole Human Genome Oligo Microarray platform from Agilent which represents over 41000 genes and transcripts to elucidate the differential gene expression when knocking down SOX4. We found about 150 genes and transcripts with more than 2 fold-change of expression. Afterwards, we confirmed the array data by real time quantitative PCR (RT-qPCR) of the genes with a decreased expression when interfering SOX4 mRNA. Within these genes, we could confirm direct transcriptional targets of SOX4 by means of binding site computation and quantitative chromatin immunoprecipitation (qChIP). This integrated approach helps us to better understand the role of SOX4 in lung carcinogenesis.
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 4019. doi:10.1158/1538-7445.AM2011-4019
Abstract 4022: Inactivation of the tumor suppressor BRG1 in lung cancer: Influence on nuclear receptors and cell differentiation
Authors: Romero-Ferraro Octavio A. , Setién Fernando , Villanueva Alberto , Coll Albert , Sanchez-Cespedes Montserrat 
Published: June 2012

Abstract
BRG1, encoding an ATPase of the SWI/SNF chromatin remodelling complex, is genetically inactivated in a variety of human solid tumors, especially non-small cell lung cancer, thus, constituting a bona fide tumor suppressor gene. However, the mechanisms that mediate the tumor suppressor function of BRG1 are not completely elucidated. We previously reported that lung tumors with amplification at any of the MYC family of genes lacked BRG1 mutations, suggesting a functional relationship between both proteins. Using isogenic lung cancer cell lines, that stably and conditionally express wild type or mutant BRG1, we found that wtBRG1 induced the up-regulation of MYC-target genes. This was accompanied by a reduction in MYC levels. Interestingly, we observed an overlap in the gene expression pattern after restoring wtBRG1 in lung cancer cells and gene expression in normal lung, indicating that BRG1 is promoting cell differentiation. In addition, the effects of BRG1 activity in lung cancer cells, i.e. changes in morphology and in gene expression depended on the presence of specific vitamins/hormones. Exposition to these compounds conferred lung cancer cells specific morphological features that were compatible with cell differentiation, only after restoring wtBRG1. Finally, using lung orthotopic mouse models we demonstrated that BRG1 was able to cause significant tumor shrinkage and delay tumor progression. Taken together our data support a tight functional relationship between BRG1 and MYC by which inactivation of BRG1 in cancer cells leads to de-regulation of MYC activity and allow refractoriness to nuclear receptor-mediated external signals impairing the control important cellular processes, such as cell differentiation, proliferation and response to inflammation.
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 4022. doi:10.1158/1538-7445.AM2011-4022
Abstract 4027: Myc controls mRNA stability through the agency of AU-binding proteins to promote lymphomagenesis
Authors: Rounbehler Robert J. , Fallahi Mohammad , Steeves Meredith A. , Li Weimin , Yang Chunying , Doherty Joanne R. , Cleveland John L. 
Published: June 2012

Abstract
Myc oncoproteins regulate transcription by binding to target genes harboring E-boxes or Initiator elements, yet these responses explain only a fraction of the genes Myc affects. mRNA turnover is controlled via binding of AU-binding proteins (AUBPs) to AU-rich elements (AREs) found within many transcripts. Expression analyses of precancerous and malignant Myc-expressing B cells revealed Myc regulates hundreds of ARE-containing genes and several AUBPs. Notably, Myc directly suppresses transcription of Tristetraprolin (TTP), an mRNA-destabilizing AUBP, and TTP suppression is a hallmark of Myc-driven lymphoma in mice and man. Furthermore, TTP has profound effects on tumorigenesis, where restoring TTP impairs Myc-induced lymphoma development and abolishes maintenance of the malignant state; thus, TTP functions as a tumor suppressor. Finally, the Myc-to-TTP pathway regulates a very select cast of ARE-containing genes that control cell proliferation and transformation. Thus, Myc utilizes AUBPs to target ARE-containing genes in its efforts to control cell fate and transformation.
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 4027. doi:10.1158/1538-7445.AM2011-4027
Abstract 4029: Inhibitor of differentiation 4 (Id4) Induces of senescence, apoptosis and cell cycle regression in prostate cancer
Authors: Carey Jason P. , Chaudhary Jaideep , Evans Ashley 
Published: June 2012

Abstract
Id4 is a member of helix loop helix (HLH) transcriptional regulator family. Unlike its other family members (Id1, 2 and 3) that promote metastasis, proliferation and invasion (tumor promoter). Id4 essentially acts as a tumor suppressor e.g. Id4 expression is lost in prostate cancer through promoter hypermethylation. However the underlying mechanism by which Id4 acts as a tumor suppressor remains to be determined. In order to investigate the molecular mechanism by which Id4 acts as a tumor suppressor, we used DU145 cell in which Id4 is epigenetically silenced. Ectopic expression of Id4 in DU145 cells resulted in the induction of several cellular processes that are reminiscent of its role as a tumor suppressor. Our results suggested that Id4 is directly linked to cell cycle control, apoptosis, senescence and induction of epithelial like morphology. There is also an upregulation in androgen receptor expression, localization to the nucleus and an atypical response to androgens in DU145 prostate cancer cells. FACS analysis using a combination of PI and Annexin V staining demonstrated the ability of Id4 to induce an S-phase arrest, and initiate apoptosis. Interestingly, Id4 promoted senescence as observed by beta-galactosidase staining. RT-PCR and western blot analysis were used to study the gene expression of apoptosis and cell cycle control genes such as: E-cadherin, p21, p27, p53, MDM2, E2F1 and, Androgen receptor. The S-phase arrest in Du145+Id4 cells was E2F-1 dependent. The increased expression of E-cadherin, p27, p21 and MDM2 in DU145+Id4 cells strengthen the hypothesis that Id4 acts as a tumor suppressor by regulating key cell cycle control and apoptosis associated genes. Re-expression of functional androgen receptor marked a dramatic change in the androgen independent prostate cancer cell type. Thus, Id4 appears to induce a total cellular reprogramming and reversal of the cancer phenotype, by influencing key regulatory pathways.
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 4029. doi:10.1158/1538-7445.AM2011-4029
Abstract 4032: SIRT1 modulates E2/ERα-associated oncogenic signaling in human breast cancer
Authors: Elangovan Selvakumar , Ramachandran Sabarish , Prasad Puttur D. , Ganapathy Vadivel , Thangaraju Muthusamy 
Published: June 2012

Abstract
SIRT1, a NAD+-dependent deacetylase, first emerged as a potential anti-aging factor by controlling senescence, but now it is also implicated in tumor development and cancer cell survival. SIRT1 is overexpressed and/or catalytically activated in a variety of human cancers, suggesting a potential role for SIRT1 in tumor promotion. SIRT1 promotes oncogenic signaling, in part, by deacetylating the tumor suppressor protein p53 resulting in its inactivation. Similarly, estrogen receptor alpha (ERα) also promotes the development and progression of hormone-dependent cancers such as breast cancer, in part, by inactivating p53 function. It is not known whether ERα and SIRT1 functionally cooperate to elicit their biologic effects. Thus, we hypothesized that there could be a functional link between ERα and SIRT1 and that this link could play a role in cellular immortalization and tumor formation in mammary epithelial cells. Using a series of coimmunoprecipitation and immunofluorescence assays, we demonstrated that ERα physically interacts and functionally cooperates with SIRT1 in breast cancer cells and that SIRT1 is necessary for ERα-induced p53 inactivation. This interaction requires active estrogen-ERα (E2-ERα) complex and catalytically active SIRT1. Functional disruption of either E2-ERα or SIRT1 dramatically reduces this interaction. Further, ERα binds to SIRT1 promoter and increases SIRT1 transcription whereas SIRT1 does not affect the expression and acetylation status of ERα. In breast cancer cells, SIRT1 inactivation or knockdown decreases E2-induced cell growth, and this process is associated with prevention of ERα-induced p53 inactivation and induction of antioxidant enzymes. Finally, mouse xenograft studies of human ER-positive breast cancer cells provide in vivo evidence for the importance of the ERα-SIRT1 complex in breast cancer growth in which deletion of SIRT1 abrogates the tumor-promoting activity of estrogen completely. These studies show that SIRT1 is essential for the promotion of E2/ERα-associated breast cancer growth and that a combination of SIRT1 inhibitors and anti-estrogens could offer a novel approach for breast cancer management.
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 4032. doi:10.1158/1538-7445.AM2011-4032