bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1786: Effect of DUSP2 on pancreatic cancer lymphatic dissemination
Authors: Tsai Shaw-Jenq , Wang Chu-An , Chang I-Heng 
Published: August 2019

Abstract
More than 90% of pancreatic cancers are originated from the exocrine ducts of the pancreas, which is called pancreatic ductal adenocarcinoma (PDAC). PDAC is notorious for the high early metastatic rate and low 5-year survival rate. Vascular endothelial growth factor C (VEGF-C), a member of the VEGF family, was first identified as the master lymphangiogenic factor in embryonic development. Overexpression of VEGF-C in cancers has been tightly linked to lymphangiogenesis and is highly associated with lymphatic invasion and metastasis; however, the underlying mechanism responsible for VEGF-C overexpression remains largely unknown. Constitutive activation of MAPK pathway was characterized as feature of pancreatic cancer. In genetic mouse model of pancreatic cancer, MAPK signaling is required to initiate and maintain the pancreatic intraepithelial neoplasia lesions. In normal cells, MAPKs mediated signaling is crucial to various cell functions and the activation can be balanced by the action of dual specificity phosphatases (DUSPs). Previously, we have demonstrated that hypoxia can suppress DUSP2 by which mediates tumor malignancy and drug resistance. Herein, we further identify that DUSP2 is a master regulator in controlling lymphangiogenesis and early lymphovascular invasion of PDAC. Expression of DUSP2 is silenced in PDAC, which contributes to aberrant production of VEGF-C. VEGF-C expression is controlled by DUSP2 at multiple levels including transcription, maturation, and extracellular vesicle-associated secretion. Our findings provide the proof of concept that blocking DUSP2/Exo-VEGF-C axis may serve as an attractive therapeutic approach to inhibit early dissemination of pancreatic cancer.
Citation Format: Shaw-Jenq Tsai, Chu-An Wang, I-Heng Chang. Effect of DUSP2 on pancreatic cancer lymphatic dissemination [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1786.
Abstract 1788: Targeting ornithine decarboxylase down-regulates multiple pathways involved in precancerous lesion formation of esophageal squamous cell cancer
Authors: Xie Yifei , Wu Qiong , Zhao Jimin , Liu Kangdong 
Published: August 2019

Abstract
Precancerous lesion of esophageal squamous cell cancer (ESCC) owns the characteristic of bidirectional instability, which can develop to cancer or reverse to normal epithelium by appropriate interference. Therefore, the feature of precancerous lesion provides possibility for ESCC chemoprevention. In the current study, we found that ornithine decarboxylase (ODC) protein level is higher in esophageal precancerous lesions compared with normal esophageal epithelium. Knocking down ODC suppresses cell proliferation and clone formation of ESCC. Moreover, difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, decreases N-nitrosomethylbenzylamine (NMBA)-induced rats’ esophageal precancerous lesions. Further molecular study indicated that ODC down-regulates p38, ERK in the MAP kinase pathway and AKT/mTOR/p70S6K pathway, which are involved in the carcinogenesis process. Overall, our results indicate that ODC may be a potential target for ESCC chemoprevention.
Citation Format: Yifei Xie, Qiong Wu, Jimin Zhao, Kangdong Liu. Targeting ornithine decarboxylase down-regulates multiple pathways involved in precancerous lesion formation of esophageal squamous cell cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1788.
Abstract 1796: p53 regulation of osteoblast differentiation is mediated through specific microRNAs
Authors: Pendleton Elisha , Shah Shivang , Couture Oliver , Kusper Teresa , Broachwalla Mustafa , Alt Lauren , Fay Michael , Chandar Nalini 
Published: August 2019

Abstract
We have previously shown a role for tumor suppressor gene p53 in the transcriptional activation of several bone-specific genes in osteoblast differentiation. In this study, we used a screen for microRNAs to look for ones that were p53 dependent and differentiation dependent. In a model of invitro osteoblast differentiation, our previous work has established that p53 levels generally increase around day 4 of differentiation and represent the timeline when p53 transcriptionally regulates bone-specific gene expression. In these experiments, we used MC3T3-E1 osteoblasts to stably reduced p53 levels using specific shRNAs. These cells were initially characterized for the reduction in p53 levels and then compared with MC3T3E1 cells stably transfected with a scrambled control (Control MC3T3E1 cells). MicroRNAs were isolated from day 0 and day 4 after treatment with differentiation promoting (DP) media. A microRNA profiling service utilizing a microarray detection system analyzed over 1000 different microRNAs in control and DP treated cells to determine differentiation specific microRNAs expression. This array provided us with information about a number of genes that underwent alterations during differentiation in a p53 dependent manner. We validated several of the changes using realtime PCR and selected two microRNAs to study in detail. These two microRNAs (mIR 34b and 140) were increased two fold during normal differentiation but showed a dramatic reduction in expression when p53 levels were reduced. We ectopically expressed these microRNAs in MC3T3-E1 cells and created stable lines. Cells carrying mIR34b showed a decrease in cell proliferation rates when compared to mIR140 expressing and control cells. P53 levels directly correlated with microRNA 34b expression but not mIR140. MiR 140 ectopic expression affected Bone morphogenetic protein expression (BMP2), an important bone anabolic agent that is also p53 regulated. Putative target binding sites for bone-specific transcription factors Runx2, SP7, Vitamin D receptor (VDR) were found for mIR34b and 140 and were utilized in luciferase reporter assays to confirm microRNA specific interactions. These studies provided evidence and confirmed for us that the p53 regulation of osteoblast differentiation is also mediated through specific microRNAs that directly target important bone-specific genes.
Citation Format: Elisha Pendleton, Shivang Shah, Oliver Couture, Teresa Kusper, Mustafa Broachwalla, Lauren Alt, Michael Fay, Nalini Chandar. p53 regulation of osteoblast differentiation is mediated through specific microRNAs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1796.
Abstract 1797: Serum microRNAs as immune modulators and biomarkers of breast cancer recurrence
Authors: Chen Lauren , Soni Mithil 
Published: August 2019

Abstract
MicroRNAs (microRNAs) are short sequences of RNA (about 22 nucleotides) that are involved in the regulation of gene expression. Previous studies have suggested that a number of microRNAs are recognized as new biomarkers for cancers. The aim of this study is to identify specific microRNAs in serum, which may serve as potential diagnostic and prognostic biomarkers and therapeutic targets for breast cancer. Quantitative real-time PCR (qRT-PCR) array analyses of microRNAs in sera from four pairs of recurrent and nonrecurrent breast cancer patients were performed. Those differentially expressed microRNAs were verified in serum samples from 42 breast cancer patients. The prognostic values of the selected microRNAs were statistically analyzed, determined by the correlation between microRNA expression and tumor parameters. High serum levels of miR-134 and miR-483-5p were found to be associated with some aggressive tumor behaviors. Kaplan-Meier analysis of four upregulated microRNAs (miR-134, miR-483-5p, miR-493-3p and miR-139-3p) indicated that serum level of miR-134 can predict tumor recurrence in breast cancer patients after primary treatment. Further functional analysis showed that overexpression of miR-134 has no significant effects on tumor growth but regulates macrophage M1/M2 polarization. Overall, our data suggested that serum microRNAs may promote tumor progression and recurrence via modulating inflammation and immune response and potentially serve as blood biomarkers for prediction of recurrence in breast cancer.
Note: This abstract was not presented at the meeting.
Citation Format: Lauren Chen, Mithil Soni. Serum microRNAs as immune modulators and biomarkers of breast cancer recurrence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1797.
Abstract 18: Doubled lifespan in APCMin/+ mice by targeting MTAP
Authors: Firestone Ross S. , Feng Mu , Schramm Vern L. 
Published: August 2019

Abstract
Humans with Familial Adenomatous Polyposis (FAP) have increased risk of colon cancer. Mice with the APCMin/+ mutation provide an animal model of FAP. Interruption of epigenetic control by preventing salvage of S-adenosylmethionine from 5′-methylthioadenosine (MTA) was tested as a potential FAP therapy. 5′-Methylthioadenosine phosphorylase (MTAP) catalyzes the phosphorolysis of MTA to adenine and methylthioribose-1-phosphate for methionine recycling. The effect of MTDIA, a transition state analogue of MTAP, was tested as an oral agent in APCMin/+ mice. Survival analysis with 10, 20 and 30 mg/kg/day oral doses of MTDIA showed a 2-fold increase in mouse lifespan at the optimal 20 mg/kg/day dose. Metabolomic analysis (mouse liver) showed significant changes in metabolites relevant to methionine metabolism. The &gt;4-fold increase in MTA, confirmed the physiologic target. Histologic analysis of intestinal tissue revealed slowed tumor progression in treated mice. RNAseq and Western blots provide additional information about the consequences of MTAP inhibition.
Citation Format: Ross S. Firestone, Mu Feng, Vern L. Schramm. Doubled lifespan in APCMin/+ mice by targeting MTAP [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 18.
Abstract 180: Defining the metastasome in colorectal cancer: Novel hypotheses on tumor progression, metastasis evolution and therapy by whole genome sequencing
Authors: Allgayer Heike 
Published: August 2019

Abstract
Metastasis poses the highest challenge for personalized therapy, partly due to incomplete understanding of its molecular evolution. This work presents the most comprehensive whole-genome study of colorectal metastasis vs. matched primary tumors. The cohort presented supports both early and late dissemination models. 65% of somatic small mutations originated from a common ancestral truncal node, with 15% of small mutations being tumor- and 19% metastasis-specific, implicating a higher mutation rate in metastases. In tumor- and metastasis-specific mutations we observed elevated levels of BRCA-ness signatures. A multistage progression model was confirmed with new components ARHGEF7/ARHGEF33, and ploidy dependent co-occurring SOX9 and HK3 mutations. We found previously undescibed recurrently mutated non-coding elements including specific ncRNAs and 3’ UTRs which will be presented at the meeting, some of them known as potential dual protagonists in metastasis and efferocytosis-/PD-L1 mediated immunosuppression. Furthermore, we discovered genomic aberrations explaining microRNA expression changes during metastasis. Moreover, we found actionable metastasis-specific lesions (which will be reported at the meeting) which would not have been detected in whole genome sequencing of the corresponding primary tumor, suggesting a reconsideration and modifications of current personalized therapy concepts to prevent metastasis. Metastasis-specific small mutations were enriched in PI3K-Akt signaling, cell adhesion, extracellular matrix but also hepatic stellate activation pathway genes, suggesting the initiation of genetic programs for site-specific colonization during metastasis. Taken together, the results presented here reveal novel components of disease progression and metastasis evolution with evidence for metastasis-specific genomic lesions relevant for personalized therapy.
Citation Format: Heike Allgayer. Defining the metastasome in colorectal cancer: Novel hypotheses on tumor progression, metastasis evolution and therapy by whole genome sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 180.
Abstract 1810: LncCGU1 and AFP serve as important prognostic marker in non-hepatitis B non-hepatitis C hepatocellular carcinoma
Authors: Lin Kwang-Huei , Lin Yang-Hsiang , Liu Yu-Chin 
Published: August 2019

Abstract
Background: Thyroid hormone (T3) and its receptor (TR) are involved in cell metabolism and cancer progression. Hypothyroidism is a significantly elevated risk factor for hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is increased in the majority of patients with HCC and may be useful in the diagnosis and follow-up of cases of HCC. The relationship between T3/TR and AFP levels in HCC is still unclear. Design: We used microarrays to compare expression profiles of lncRNAs in HepG2-TRα1 cells treated with/without T3 and HCC specimens. The profiling results were validated using qRT-PCR. The overall survival and recurrence-free survival were analyzed using Kaplan-Meier method and further confirmed by online available datasets. Results: In the current study, long non-coding RNA CGU1 was downregulated by T3/TR in vitro. Notably, α-fetoprotein (AFP) mRNA levels were downregulated by T3/TR through repression of CGU1. Notably, AFP mRNA is strongly positively correlated with CGU1 and unfavorable prognosis in non-hepatitis B/non-hepatitis C HCC (NBNC-HCC) group patients. Conclusions: our data collectively suggest that T3/TR/ CGU1/AFP act as a potential prognostic marker in NBNC-HCC.
Citation Format: Kwang-Huei Lin, Yang-Hsiang Lin, Yu-Chin Liu. LncCGU1 and AFP serve as important prognostic marker in non-hepatitis B non-hepatitis C hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1810.
Abstract 1811: The long noncoding RNA KIAA0125 is aberrantly expressed in ameloblastomas
Authors: Sousa Silvia F. , Diniz Marina G. , França Josiane A. , Vilas-Boas Fabricio A. , Souza Fabricio T. , Calin George A. , Gomez Ricardo S. , Gomes Carolina C. 
Published: August 2019

Abstract
Long noncoding RNAs (lncRNAs) are transcribed RNA molecules that can interact with DNA or RNA, transcription factors, histones and other chromatin modifying proteins, affecting the expression level of a broad spectrum of genes. Because of their tissue-specific expression characteristics, lncRNAs hold strong promise as novel biomarkers and therapeutic targets for diseases. High-density whole-genome microarray analysis in ameloblastomas, an aggressive odontogenic tumor, and in adenomatoid odontogenic tumor (AOT), an indolent one, showed a high frequency of copy number alteration at chromosome band 14q32.33, which encompasses the lncRNA gene KIAA0125. To understand molecular mechanisms associated with their biological behavior and considering the copy-number gains observed at 14q32.33, we aimed to investigate the expression levels of the lncRNA KIAA0125 in ameloblastomas and in AOTs. The University Ethics Committee approved this study and patients signed informed consent. Thirteen frozen samples were included: five solid/multicystic ameloblastomas, four AOT, and four dental follicles. qPCR reactions were performed in triplicates and the relative changes in gene expression were obtained using the 2^-ΔΔCt formula. The reference gene HPRT1 was used for normalization and the human keratinocyte HaCat cell line was used as calibrator. Differences in the relative changes in gene expression between two groups of samples were assessed and the significance level was set at 0.05. All samples expressed more KIAA0125 than the calibrator. The ameloblastoma group showed higher expression levels of KIAA0125 when compared to dental follicles (p=0.042), while there was no difference between the expression in ameloblastomas and AOT (p&gt;0.05). The expression levels of KIAA0125 in AOT were not different from that of the dental follicle. Our findings suggest that lncRNA KIAA0125 is likely involved in ameloblastoma pathobiology. LncRNAs hold strong promise as therapeutic targets, and experimental validation of this lncRNA functions may lead to tailored therapies targeting KIAA0125 in extensive and recurrent ameloblastomas.
Citation Format: Silvia F. Sousa, Marina G. Diniz, Josiane A. França, Fabricio A. Vilas-Boas, Fabricio T. Souza, George A. Calin, Ricardo S. Gomez, Carolina C. Gomes. The long noncoding RNA KIAA0125 is aberrantly expressed in ameloblastomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1811.
Abstract 1814: Carboxyl-terminal truncated HBx represses lncRNA-LOC to promote cell metastasis
Authors: Lin Yang Hsiang , Yeh Chau-Ting , Lin Kwang-Huei 
Published: August 2019

Abstract
Hepatocellular carcinoma (HCC) is one of the most common and aggressive human malignancy in the world. The poor prognosis of HCC is partly due to a high incidence rate of extrahepatic metastases. Several studies have shown that the relative risk of HCC among hepatitis B virus (HBV) carrier is higher than non-carrier group. Among the four proteins translated by HBV, X-gene (HBx) has been correlated with oncogenesis of HCC. Meanwhile, it is well known that random HBV genome integration can cause truncation of the HBV genome, especially on the HBx gene locus at the C-terminus (designated as Ct-HBx). The discovery of long non-coding RNA (lncRNA) transcripts has dramatically expanded our understanding of cell biology, especially in cancer. However, the underlying molecular mechanisms of lncRNAs that mediate the metastatic cascade and cancer progression remain largely unclear in liver cancer. In this study, lncRNA-LOC is significantly downregulated in HCC and negatively correlated with overall survival in HCC patients. LncRNA-LOC is negatively regulated by Ct-HBx in vitro and in vivo (HCC specimens). Two novel transcripts of LncRNA-LOC in HepG2 and Huh7 cell lines were identified by 5’ and 3’ rapid amplification of cDNA ends assays, respectively. Overexpression of lncRNA-LOC induced marked inhibition of cell migration, invasion and cell proliferation in vitro. On the other hand, these phenotypes were reversed upon knockdown of lncRNA-LOC in cells. Mechanically, levels of p-STAT3 (Tyr705 and Ser727), p-c-Jun (Ser63) and Snail were decreased in lncRNA-LOC-overexpressing cells, compared to control cells. Our data collectively highlight that novel regulatory associations among lncRNA-LOC, Ct-HBx, p-STAT3, p-c-Jun and Snail are an important determinant of metastasis in HCC cells and support the potential utility of lncRNA-LOC as a therapeutic strategy for HCC.
Citation Format: Yang Hsiang Lin, Chau-Ting Yeh, Kwang-Huei Lin. Carboxyl-terminal truncated HBx represses lncRNA-LOC to promote cell metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1814.
Abstract 181A: PIN1 and FOXP3 regulate SKP2 expression
Authors: Yang Wei-Hsiung , Wang Chiung-Min , Yang William H. 
Published: August 2019

Abstract
S-phase kinase-associated protein 2 (SKP2), a component of the E3 ubiquitin ligase SKP1-CUL1-Fbox complex, acts as an oncogene/oncoprotein as evidence suggests that overexpression of SKP2 results in cell cycle dysregulation and tumorigenesis as well as associates with poor prognosis in numerous cancers. The unique peptidyl-propyl isomerase PIN1, which isomerizes the cis-trans peptide bond between pSer/pThr and proline, regulates its target proteins’ cell localization, stability, and function. However, whether SKP2 is the target protein of PIN1 remains unknown. Herein, we demonstrate that SKP2 expression is regulated by PIN1 and FOXP3. First, we observed that knock-down PIN1 using siRNAs reduced SKP2 protein level in several cancer cell lines (MCF7, PC3, DU145, HepG2, and JEG3 cells). Secondly, we found that overexpression of PIN1 increased SKP2 protein level. Furthermore, PIN1 dose-dependently enhanced SKP2 promoter activity in gene reporter assay. Since FOXP3 is a known transcriptional repressor for the oncogene SKP2, we investigated whether PIN1 affects FOXP3-mediated SKP2 expression. Interestingly, we observed that PIN1 dose-dependently counteracted FOXP3-mediated SKP2 promoter activity. Finally, we demonstrated that mutations on PIN1 (W34A) and FOXP3 (Y342F) abolished PIN1-mediated and FOXP3-mediated SKP2 expression, respectively. Taken together, our results suggest that PIN1 functions as a novel regulator of SKP2 and with FOXP3 may be involved in tumor development and progression.
Citation Format: Wei-Hsiung Yang, Chiung-Min Wang, William H. Yang. PIN1 and FOXP3 regulate SKP2 expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 181A.