bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3050: Transcriptome sequencing identifies oncogenic microRNA signatures related to NF-kB, TP53 and Notch family members in head and neck squamous cell carcinoma.
Authors: Saleh Anthony D. , Si Han , Yang Xingping , Coupar Jamie , Chen Zhong , Van Waes Carter 
Published: August 2014

Abstract
MicroRNA dysregulation has been shown to be nearly universal in cancer biology, driving oncogenic signaling networks. However, microRNA mediated global regulatory mechanisms underlying malignant phenotypes of head and neck squamous cell carcinoma (HNSCC) remain unclear. In this study, we have performed genome-wide small RNA sequencing on a panel of nine HNSCC cell lines and three normal primary oral keratinocyte cell lines, as well as matched primary tumor and normal tissues using the SOLiD parallel sequencing platform. A panel of microRNAs with altered expression was identified, including several novel oncogenic microRNAs which are upregulated in parallel with altered activation of NF-KB c-REL, TP53 family members ΔNp63α and TAp73, and potentially involved in the down-modulation of p53 and Notch1, two genes most often mutated or inactivated in HNSCC. To examine the hypothesis that these microRNAs could potentially be regulated by NF-KB and p53 pathways, NF-KB inducer TNF-α was used to treat an HNSCC cell line with high expression of mtTP53, ΔNp63α and TAp73. Genome-wide small RNA sequencing revealed significant changes in microRNA expression modulated by TNF-α that overlaps with the panel of constitutively dysregulated microRNAs in HNSCC. Furthermore, genome-wide ChIP-sequencing revealed that TNF-α modulated DNA binding activities of c-REL, ΔNp63α and TAp73 aligned within the regulatory regions of several differentially expressed microRNAs. Modulation of these microRNAs with anti-miR repression altered cell cycle and reduced proliferation in HNSCC cell lines, which confirmed the oncogenic activity of the microRNAs and their potential for therapeutic targeting.
Citation Format: Anthony D. Saleh, Han Si, Xingping Yang, Jamie Coupar, Zhong Chen, Carter Van Waes. Transcriptome sequencing identifies oncogenic microRNA signatures related to NF-kB, TP53 and Notch family members in head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3050. doi:10.1158/1538-7445.AM2013-3050
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 3056: miR-125b suppresses p14ARF and modulates p53-dependent and p53-independent apoptosis in prostate cancer cells.
Authors: Shi Xu-Bao , Amir Sumaira , Ma Ai-Hong , Xue Lingru , deVere White Ralph W. 
Published: August 2014

Abstract
Increasing evidence has revealed that miR-125b functions as a potential oncogene in different types of human cancer. Our previous studies demonstrated that miR-125b directly targets p53, Puma and Bak1 in human prostate cancer (CaP). To further elucidate the role of miR-125b in modulating the p53 network, we utilized a bioinformatics approach to identify miR-125b-regulated, CaP-relevant tumor suppressor gene, and identified p14ARF gene as a miR-125b target. We first evaluated the effect of miR-125b on the regulation of p14ARF expression, and found that miR-125b treatment induced reduction of p14ARF by 80% in LNCaP CaP cells and 60% in 22Rv1 CaP cells. Conversely, anti-miR-125b increased the p14ARF level by 40% in LNCaP and 30% in 22Rv1. We then performed luciferase assay to validate that the miR-125b binding site in the 3’UTR of p14ARF mRNA is responsible for the regulation of p14ARF by miR-125b. Since p14ARF accelerates Mdm2 degradation, resulting in p53 up-regulation, we thus assessed the effect of miR-125b on the expression of Mdm2 and p53. Compared with miRNA control, miR-125b treatment induced a dramatic increase in Mdm2 and a significant reduction of p53 in CaP cell lines, as well as in miR-125b-overexpressed xenograft tumor. Additionally, miR-125b treatment resulted in a reduction of interaction between p14ARF and Mdm2. Next, we examined the effect of miR-125b on CaP cell proliferation. Both LNCaP and 22Rv1 cells were transfected with miR-125b and cell proliferation was determined by clone formation assay. When compared with the control, miR-125b treatment increased clonogenic survival of CaP cells, while anti-miR-125b caused a dramatic reduction in the number of colonies. We evaluated the effect of downregulation of miR-125b on apoptosis in p53-positive 22Rv1 CaP cells. Data from TUNEL assay demonstrated that anti-miR-125 caused 63% of cells to undergo apoptosis. Similarly, in p53-negative PC3 CaP cells, miR-125b treatment induced a 2-fold increase in survival, while anti-miR-125b caused 50% of cells to undergo apoptosis. In summary, we observed that overexpression of miR-125b negatively regulates the expression of p14ARF, resulting in promotion of cell proliferation and inhibition of apoptosis. Inactivation of miR-125b using anti-miR-125b affects apoptosis involving both p53-dependent and p53-independent pathways. Therefore, our data suggest that miR-125b has a great potential to be used as a therapeutic target for CaP treatment.
Citation Format: Xu-Bao Shi, Sumaira Amir, Ai-Hong Ma, Lingru Xue, Ralph W. deVere White. miR-125b suppresses p14ARF and modulates p53-dependent and p53-independent apoptosis in prostate cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3056. doi:10.1158/1538-7445.AM2013-3056
Abstract 3077: TMPRSS2-ERG regulation of miRNA in prostate cancer.
Authors: Kim Jung , Wu Longtao , Jin Hong-Jian , Zhao Jonathan , Yu Jindan 
Published: August 2014

Abstract
Prostate cancer is the cause of the second highest number of cancer related deaths in men in the United States, with the highest number of new estimated cases every year. In addition, the survival rate in localized and regional prostate cancer is 100%, while metastatic prostate cancer is about 29%, with a wide spectrum of biological deregulations. MicroRNA (miRNA) is a small non-coding RNA, about 22 nucleotides long, that mostly targets the 3’UTR of a gene for translational repression or mRNA degradation. More recently, miRNAs have been shown to play an important role in tumorigenesis, cancer progression, and metastasis. MiR-200c is one of the miRNA widely studied in cancer, as it has a role in regulating epithelial-mesenchymal transition (EMT). One of the ways in which miR-200c inhibits EMT is through its ability to downregulate ZEB1, an EMT activator that primarily functions by repressing E-cadherin. ERG is a transcription factor that is often fused with TMPRSS2 in prostate cancer and promotes cancer progression. In our study, we investigated the interaction of ERG and miR-200c, two factors that play important role in cancer progression, in prostate cancer.
First, we identified ERG regulated miRNAs through utilizing miRNA profiling in LNCaP cells that were overexpressing ERG and in VCaP cells that have ERG knocked down. We selected miRNAs that are repressed upon ERG overexpression and derepressed upon ERG knockdown and also overlapped the results with ERG ChIP-seq data to identify ERG regulated miRNAs. Through this process we discovered that miR-200c is a good ERG-targeted miRNA. To validate the bioinformatics results, we used ERG overexpression in LNCaP and ERG knockdown in VCaP to measure mature miR-200c levels by miRNA assay. In addition, ERG ChIP-qPCR and miR-200c promoter luciferase assays showed that ERG binds at the miR-200c promoter. Next, to identify functional roles of miR-200c in ERG overexpressed cells, we performed invasion and migration assays to show that miR-200c plays an important role in the inhibition of ERG-mediated cancer progression.
This study identifies an important factor, miR-200c, whose loss mediates the progression of TMPRSS2:ERG fusion-positive prostate cancer. According to our results, it might be possible to use miR-200c as a future therapeutic for ERG positive patients. This work was supported in part by the Research Scholar Award RSG-12-085-01 (to J.Y.) from the American Cancer Society, Department of Defense PC080665 (to J.Y.) and NRSA pre-doctoral fellowship T32 CA080621 (to J.K.).
Citation Format: Jung Kim, Longtao Wu, Hong-Jian Jin, Jonathan Zhao, Jindan Yu. TMPRSS2-ERG regulation of miRNA in prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3077. doi:10.1158/1538-7445.AM2013-3077
Abstract 3078: Mifepristone suppresses triple-negative breast cancer cell growth via miR-153 mediated down-regulation of KLF5 expression.
Authors: Liu Rong , Chen Ceshi 
Published: August 2014

Abstract
Triple-negative breast cancer (TNBC) is one of the most malignant breast cancers without effective therapeutic approaches currently. It is reported that KLF5 is over-expressed in TNBC; and KLF5 depletion suppresses TNBC cell proliferation, cell survival and tumor growth in vivo significantly, which implies that KLF5 may be a therapeutic target for TNBC treatment. As a progesterone receptor antagonist, mifepristone (MIF) has been found to have anti-tumor activity in multiple hormone-dependent cancers, including luminal type breast cancers. Interestingly, we found that MIF is also able to suppress KLF5 protein expression in TNBC cell and inhibit TNBC cell growth in vitro and in vivo. We further demonstrated that MIF does not suppress KLF5 mRNA expression at all, but down-regulates KLF5 protein level via up-regulating miR-153 expression in TNBC cells. We found miR-153 mimics can down-regulates KLF5 protein level in TNBC cells similar to MIF does; and consistently, miR-153 inhibitor rescues MIF-induced down-regulation of KLF5 protein expression. Taken together, our findings suggest that MIF is able to inhibit TNBC growth possibly via suppressing KLF5 expression; and our research may provide a new possible chemotherapeutic for the treatment of TNBC.
Citation Format: Rong Liu, Ceshi Chen. Mifepristone suppresses triple-negative breast cancer cell growth via miR-153 mediated down-regulation of KLF5 expression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3078. doi:10.1158/1538-7445.AM2013-3078
Abstract 3084: miR509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF alpha.
Authors: Xing Fei , Okuda Hiroshi , Kobayashi Aya , Pandey Puspa R. , Sharma Sambad , Mo Yin-Yuan , Liu Yin , Wu Kerui , Watabe Kounosuke 
Published: August 2014

Abstract
Brain metastasis of breast cancer profoundly affects the cognitive and sensory functions as well as morbidity of patients, and the rate of one year survival among these patients remains less than 20%. Because of the location of metastatic lesions, a surgical approach is limited and most chemotherapeutic drugs are ineffective due to the blood brain barrier (BBB). Despite this clinical importance, the molecular basis of breast tumor metastasis to the brain is poorly understood. Recent active research in microRNA identified a series of this type of molecules that are involved in tumor progression in various tumors as oncogenes and tumor suppressors. In this study, we have isolated RNA from Formalin-Fixed Paraffin-Embedded (FFPE) samples obtained from primary breast tumors and also from brain metastatic lesions followed by microRNA profiling. The results of our profile analysis for these samples revealed that primary tumor samples expressed significantly high level of miR509 compared to brain metastatic lesions. We also found that this microRNA was capable of modulating two essential genes for invasion, RhoC and TNF alpha. Interestingly, high expression of TNF alpha was significantly and inversely correlated to brain metastasis-free survival of breast cancer patients. Importantly, we found that the expression of miR509 significantly suppressed the ability of cancer cells to metastasize to the brain in our animal model. We also examined the expression of TNF alpha in brain-metastatic lesions and found that it was indeed significantly up-regulated. Furthermore, the results of our in vitro experiments indicate that miR509 attenuates the abilities of invasion of breast cancer cells by modulating the RhoC expression. These results suggest that miR509 may serve as a biomarker or therapeutic targets for brain metastasis of breast cancer.
Citation Format: Fei Xing, Hiroshi Okuda, Aya Kobayashi, Puspa R. Pandey, Sambad Sharma, Yin-Yuan Mo, Yin Liu, Kerui Wu, Kounosuke Watabe. miR509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF alpha. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3084. doi:10.1158/1538-7445.AM2013-3084
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 3092: Deregulation of miR-10b in osteosarcoma.
Authors: Chen K. Amy , Sand Jordan P. , Janeway Katherine A. , Orkin Stuart H. 
Published: August 2014

Abstract
Osteosarcoma (OS) is the most common primary bone malignancy found in children and adolescents, but the underlying molecular pathogenesis is not yet well understood. Utilizing a genetically engineered mouse model of OS that faithfully recapitulates salient features of the human disease, we are able to examine potential molecular contributions, such as that of a class of small, regulatory RNAs called microRNAs (miRNAs), in the processes of tumor proliferation and tumor progression and/or metastasis.
MiRNA expression profile of tumors isolated from primary and secondary (metastatic) tumor sites of the mouse model revealed significant differential expression of miRNAs between the two groups. MiR-10b was significantly down-regulated in metastatic tumors in comparison with their primary counterparts, and thus was hypothesized to play important roles in the process of metastatic progression and/or tumorigenesis. To determine its impact on invasiveness and/or proliferation of the tumor cells, miR-10b was re-expressed in metastatic cell lines and introduced through tail-vein or intramuscular injections into scid/nude mice. Quantitative analysis using a bioluminescence imaging system showed delayed metastatic progression, lessened pulmonary tumor burden, as well as decreased primary tumor size in animals injected with tumor cells over-expressing miR-10b as compared to the controls. These data suggest that miR-10b down-regulation contributes to the processes of metastasis and tumorigenesis in OS through altered interaction with its target genes. Currently, putative miR-10b gene targets generated by microarray and RNA-seq analysis are being validated to provide a better understanding of the molecular mechanisms underlying miR-10b regulation in OS, and to facilitate the discovery of pathways amenable to manipulation with novel therapeutics.
Citation Format: K. Amy Chen, Jordan P. Sand, Katherine A. Janeway, Stuart H. Orkin. Deregulation of miR-10b in osteosarcoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3092. doi:10.1158/1538-7445.AM2013-3092
Abstract 3112: The homeoprotein DLX4 induces topoisomerase IIα expression but reduces sensitivity of tumor cells to topoisomerase II poisons.
Authors: Trinh Bon Q. , Ko Song Yi , Barengo Nicolas , Lin Shiaw-Yih , Naora Honami 
Published: August 2014

Abstract
Chemotherapeutic drugs such as anthracyclines and etoposide that target topoisomerase II (TOP2) induce tumor cell death by causing accumulation of DNA double-strand breaks (DSBs). Experimental studies have shown that overexpression of topoisomerase IIα (TOP2A) increases sensitivity to TOP2 poisons. However, the clinical value of TOP2A in predicting responsiveness to TOP2 poisons has been controversial and it is not known why some TOP2A-overexpressing tumors respond poorly to these drugs. We identified that expression of TOP2A, the gene encoding TOP2, is induced by DLX4, a homeoprotein that is overexpressed in breast and ovarian cancers. Analysis of breast cancer datasets revealed that TOP2A-High cases that expressed DLX4 at low levels responded more favorably to anthracycline-based chemotherapy than TOP2A-High cases that also highly expressed DLX4. Overexpression of TOP2A alone in tumor cells increased sensitivity to TOP2 poisons. However, DLX4 decreased sensitivity to these drugs irrespective of its induction of TOP2A. We identified that DLX4 stimulates repair of DSBs and interacts with Ku proteins that are components of the non-homologous end-joining machinery. DLX4 did not reduce levels of TOP2 poison-induced DSBs in Ku-deficient cells, but reduced the level of DSBs when Ku was reconstituted in these cells. Taken together, our findings indicate that DLX4 induces TOP2A expression, but reduces the sensitivity of tumor cells to TOP2 poisons by stimulating Ku-dependent repair of DSBs. These dual and opposing effects of DLX4 could explain why some tumors with elevated TOP2A levels are not highly sensitive to TOP2 poisons.
Citation Format: Bon Q. Trinh, Song Yi Ko, Nicolas Barengo, Shiaw-Yih Lin, Honami Naora. The homeoprotein DLX4 induces topoisomerase IIα expression but reduces sensitivity of tumor cells to topoisomerase II poisons. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3112. doi:10.1158/1538-7445.AM2013-3112
Abstract 3132: Beta-catenin regulates c-Myc and CDKN1A expression in breast cancer cells.
Authors: Xu Jinhua , Chen Yinghua , Khramtsov Andrey , Huo Dezheng , Goss Kathleen , Olopade Olufunmilayo I. 
Published: August 2014

Abstract
Basal-like breast cancer (BLBC) is associated with a poor prognosis and lacks therapeutic targets. The molecular pathways leading to the development of basal-like tumors are not well understood. We reported recently that nuclear and cytosolic accumulation of beta-catenin was enriched in BLBC, suggesting Wnt pathway activation in this specific subtype. c-Myc has been placed as a downstream effector of Wnt/beta-catenin pathway in colorectal cancer. However, exactly how the Wnt pathway regulates c-Myc in breast cancer and the biological significance of this regulation are poorly understood.
In this study, we found that c-Myc is highly expressed in the basal-like subtype in comparison to the other four breast cancer subtypes by IHC staining. In addition, we confirmed the concordant expression of beta-catenin and c-Myc in basal-like breast tumors. Both c-Myc and beta-catenin proteins are highly expressed in the basal-like cell lines in comparison with non-basal-like cell lines. After silencing beta-catenin using siRNA, c-Myc expression was decreased in none-BLBC cells. In contrast, c-Myc mRNA and protein expression was up-regulated in the BLBC cell lines, suggesting that beta-catenin regulates c-Myc expression in a cell type dependent manner in breast cancer. Although we did not detect any TCF promoter activity in all breast cancer cell lines, decreased c-Myc promoter activity was observed after inhibiting beta-catenin by siRNA in non-BLBC cells; however, inhibition of beta-catenin or over-expression of dominant-negative LEF had no effect on c-Myc promoter activity in BLBC cell lines. In contrast, CDKN1A mRNA and p21 protein expression were significantly increased in all breast cancer cell lines upon beta-catenin silencing. Interestingly, inhibiting beta-catenin expression alone does not induce apoptosis in breast cancer cell lines despite c-Myc regulation,, but we observed a modest increase of cells in G1 and decrease of cells in S phase in the cell lines with beta-catenin silencing. Collectively, these findings suggest that the regulation of c-Myc in breast cancer cells is dependent on the molecular subtype, and that beta-catenin-mediated control of c-Myc and p21 may control the balance of cell death and proliferation in breast cancer by both TCF-dependent and TCF-independent mechanisms.
Citation Format: Jinhua Xu, Yinghua Chen, Andrey Khramtsov, Dezheng Huo, Kathleen Goss, Olufunmilayo I. Olopade. Beta-catenin regulates c-Myc and CDKN1A expression in breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3132. doi:10.1158/1538-7445.AM2013-3132
Abstract 3134: Exomic landscape of somatic variation in uterine leiomyomas.
Authors: Mäkinen Netta , Vahteristo Pia , Aaltonen Lauri A. 
Published: August 2014

Abstract
Uterine leiomyomas, or fibroids, are benign tumors for which the lifetime risk in women by the age of 50 has been estimated to be nearly 70%. Fibroids arise from smooth muscle cells of the myometrium. Regardless of their benign nature, leiomyomas can cause difficult symptoms, such as excessive bleeding, abdominal pain, pregnancy complications, and infertility. They are also the most common cause for hysterectomy. Considering the prevalence of these lesions, relatively little is known about the mechanisms of their growth and tumorigenesis. We have previously showed by exome sequencing that mediator complex subunit 12 (MED12) exon 2 is mutated in approximately 70% of sporadic uterine leiomyomas. The aim of this study is to examine molecular genetic background of MED12 mutation positive lesions, as well as to identify additional recurrent somatic variants from those fibroids that do not harbor MED12 mutations and cannot be explained for example by mutations in fumarase hydratase (FH) which has already previously been associated with the predisposition to uterine leiomyomas. We performed whole exome sequencing of 28 uterine leiomyomas and their corresponding myometrium pairs. Exome sequencing data of the uterine leiomyomas was filtered against data from the respective normal tissue, the 1000Genomes Project (93 FIN samples, Phase 1 release v2), rs-coded SNPs taken from the Database of Single Nucleotide Polymorphisms (dbSNP, Build 132), and 70 in-house control exomes to exclude germ line variation from the analysis. Both exomic regions and sequences within two base pairs of the exon-intron boundaries were analyzed. Synonymous coding and intronic variants were not included to the study. All potentially significant mutations and their somatic status were validated by Sanger sequencing. Based on our results, uterine leiomyomas harbor less mutations than malignant tumors. We have not identified mutations in genes, such as TP53 or PTEN, which are associated with tumor malignancy. In addition to MED12, there are no other recurrent point mutations or small insertion-deletion type of mutations in sporadic uterine leiomyomas. Our results emphasize the major role of MED12 in tumorigenesis of these lesions.
Citation Format: Netta Mäkinen, Pia Vahteristo, Lauri A. Aaltonen. Exomic landscape of somatic variation in uterine leiomyomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3134. doi:10.1158/1538-7445.AM2013-3134