bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4426: Alcohol consumption and hepatitis B-associated microRNAs in hepatocellular carcinoma
Authors: Li Pin Xue , Zheng Hao , Saad Maarouf A. , Zou Angela E. , Wang Xiaoqi , Kwok James G. , Korrapati Avinaash , Qu Yuanhao , Honda Thomas K. , Wang-Rodriguez Jessica , Ongkeko Weg M. 
Published: July 2017

Abstract
Hepatocellular carcinoma (HCC) affects more than 500,000 new patients each year and is characterized by fast growing, heterogeneous tumors and low five-year survival rates. Despite the identification of HCC risk factors, including alcohol consumption and chronic hepatitis B (HBV) infection, early diagnosis of HCC and molecular understanding of how these risk factors promote HCC both individually and in combination remain elusive. microRNAs (miRNAs), non-coding transcripts ~22 nt in length, have emerged as central mediators of post-transcriptional and translational gene regulation, and have been increasingly implicated in the initiation and progression of many cancers, including HCC. However, the dysregulation profile of miRNAs in HCCs of varying etiologies remains largely unexplored. To identify dysregulated miRNAs specifically associated with alcohol use or with HBV in HCC patients, we analyzed next-generation RNA-sequencing data from 234 HCCs in The Cancer Genome Atlas (TCGA). Through differential expression analyses on cohorts stratified by alcohol consumption and HBV status, we discovered 10 miRNAs specifically dysregulated in alcohol-associated HCCs and 251 miRNAs specifically dysregulated in HBV-associated HCCs (FDR &lt; 0.05). Among these, two miRNAs, miR-944 and miR-223-3p, significantly overexpressed in HCC alcohol consumers, exhibited additional correlations with patient survival, tumor stage, and mutations in CTNNB1, MUC16 and TNN (p &lt; 0.05). We subsequently validated the upregulation of miR-944 and miR-223-3p in vitro following treatment of both normal liver and HCC cell lines with biologically relevant doses of alcohol and acetaldehyde, the first breakdown metabolite of ethanol. Knockdown of miR-944 and miR-223-3p significantly reduced cellular proliferation in both acetaldehyde-treated and untreated normal and HCC cell lines, and resulted in increased sensitivity to cisplatin. Inhibition of both miRNAs in HCC cell lines also restored the expression of several tumor suppressor genes targeted by miR-944 and miR-223-3p. Taken together, our findings enhance knowledge of the respective roles of miRNAs in alcohol- and HBV-mediated HCC, and highlight the increased transcriptomic resolution afforded by etiology-specific studies of cancer pathogenesis and progression.
Note: This abstract was not presented at the meeting.
Citation Format: Pin Xue Li, Hao Zheng, Maarouf A. Saad, Angela E. Zou, Xiaoqi Wang, James G. Kwok, Avinaash Korrapati, Yuanhao Qu, Thomas K. Honda, Jessica Wang-Rodriguez, Weg M. Ongkeko. Alcohol consumption and hepatitis B-associated microRNAs in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4426. doi:10.1158/1538-7445.AM2017-4426
Abstract 4428: A miRNA signature linked to human environmental risk defined from carcinogen-induced and genetically-driven colon carcinogenesis models
Authors: Chen Ying-Shiuan , Wang Rong , Dashwood Wan-Mohaiza , Löhr Christiane , Williams David E. , Ho Emily , Mertens-Talcott Susanne , Dashwood Roderick H. 
Published: July 2017

Abstract
Heterocyclic amines (HCAs) produced during high-temperature cooking have been studied extensively in terms of their genetic effects, but recent work has implicated epigenetic mechanisms involving non-coding RNAs. We reported that colon tumors induced in the rat by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) have altered microRNA (miRNA) signatures linked to dysregulated pluripotency factors, such as c-Myc and Krüppel-like factor 4 (Klf4). The corresponding miRNAs prioritized from PhIP-induced colon tumors were examined in other target organs from a one-year carcinogenicity bioassay, and compared with miRNAs dysregulated in the Apc-mutant polyposis in rat colon (Pirc) genetic model. Multiple let-7 family members were downregulated in colon, skin, lung, small intestine, and Zymbal’s gland tumors, and were associated with Myc and Hmga2 upregulation. A “PhIP miRNA signature” with the profile mir-21high | mir-126low | mir-29low | mir-215low | mir-145low was linked to reduced expression of Klf4 in multiple target organs of the rat, and was predictive of poor prognosis in human pan-cancer and colorectal cancer datasets (https://cancergenome.nih.gov/). Findings from The Cancer Genome Atlas suggested that PhIP signature miRNAs might serve as an arbiter of HCA exposure, defining a subset of human tumors linked to environmental carcinogen exposure. We conclude that future studies should examine the miRNA signatures of other HCAs, and determine their possible predictive value for human risk assessment. This work was supported in part by NIH grants CA090890, CA122959, ES00210, and ES023512, the John S. Dunn Foundation, and a Chancellor’s Research Initiative. We are most thankful to Robert Hawk for providing a graduate student fellowship in aid of Y-S Chen.
Citation Format: Ying-Shiuan Chen, Rong Wang, Wan-Mohaiza Dashwood, Christiane Löhr, David E. Williams, Emily Ho, Susanne Mertens-Talcott, Roderick H. Dashwood. A miRNA signature linked to human environmental risk defined from carcinogen-induced and genetically-driven colon carcinogenesis models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4428. doi:10.1158/1538-7445.AM2017-4428
Abstract 4429: An exhaled microRNA panel interrogation and validation as risk biomarkers for lung cancer
Authors: Spivack Simon D. 
Published: July 2017

Abstract
Background: There is a need for non-invasive airway-based biomarkers in lung carcinogenesis for both risk assessment of the ex-smoker, and earlier diagnosis. Recent studies have revealed that microRNAs play important regulatory roles in carcinogenesis. Exhaled breath condensate (EBC) contains airway lining fluid molecules, including nucleic acids, presumably in part from epithelial cellular origins. Here we further develop and begin validation of the detection of microRNAs in EBC from lung cancer patients and controls.
Methods: Exhaled breath condensate (EBC) was collected non-invasively, using a handheld device in ambulatory subjects. MicroRNA expression profiling using RNA-specific RT-qPCR was performed in EBC in an initial batch (E) of 88 individuals (41 lung cancer cases, 47 controls), and a second batch D of 88 individuals (41, cases and 47 controls). We generated a 39 miR panel based on literature-derived microRNAs, combined with a lung tissue-based discovery effort we have performed using microRNA-seq on lung tumors and surrounding non-tumor tissue. The qPCR primers were designed using our previously published RNA-specific realtime RT-PCR technique. All samples were run twice with positive and negative controls.
Results: Qualitative analyses of the first donor batch E was performed on 39 microRNAs measured in 41 cases and 47 controls. Chi-square analysis (univariate) within the training set (batch E) revealed that exhaled miR-31, 33, 105, 200b, 944, 1269a were significantly different between the initial set of cases and controls; their absence marked the cases. In the validation batch (D) preliminary analysis, exhaled miRs 200b (this time present in cases, p=0.044) and 944 (again absent in cases, p=0.052) were case-control discriminant. In addition, test set batch D showed case-control discrimination for additional miRs 130b-3p (present in cases, p=0.035), 212 (absent in cases, p=0.009), 1910a (absent in cases, p=0.006) and other microRNAs that were not seen in the qualitative training set (batch E). Importantly, multi-miR discriminant signatures, quantitative analysis, and risk ROC/modelling analyses are pending as of this AACR abstract deadline.
Conclusion: This new exhaled biomarker platform can yield case-control discriminant microRNA sets, including a subset of miRs that can validate in test sets. Once further distilled and validated, our goal is to apply this non-invasive biomarker approach to prospective cohorts for non-invasive lung cancer risk assessment, in order to better select higher risk individuals who should undergo CT screening.
Note: This abstract was not presented at the meeting.
Citation Format: Simon D. Spivack. An exhaled microRNA panel interrogation and validation as risk biomarkers for lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4429. doi:10.1158/1538-7445.AM2017-4429
Abstract 4444: MicroRNA hsa-miR-145 expression in hepatocellular carcinoma correlates with patient survival
Authors: Nakajima Go , Hayashi Kazuhiko 
Published: July 2017

Abstract
Aim: MicroRNAs (miRNAs) are known as one of the regulator of gene expression at a post-transcriptional level. Previous study from our group identified forty nine miRNAs that are expressed differentially by comparing 26 pair samples of hepatocellular carcinoma (HCC) tumor tissue and non-tumor liver tissue using next-generation sequencer system, and hsa-miR-145, one of the candidate miRNA was chosen for this validation study. The expression of hsa-miR-145 in validation set HCC samples were measured by real-time PCR, and were examined the correlation between the miRNA expression and clinical data.
Patients and Methods: Forty-four patients diagnosed as HCC had undergone surgical removal from 1991 to 1997 at the Department of Surgery, Institute of Gastroenterology, Tokyo Women’s Medical University, Japan. The formalin-fixed paraffin embedded samples were prepared using the standard protocol. The paraffin blocks were cut into 10 micrometer sections, and the tumor and its adjacent non-tumor liver tissue were collected using laser-captured microdissection and total RNA including miRNA fraction were isolated. After synthesized cDNA using miRNA specific primer, real-time PCR was performed using miRNA specific primer/probe.
Results: The expression level of hsa-miR-145 was down-regulated in tumor compared to non-tumor liver tissue (P=0.0004). The patients were divided into two groups, higher/lower expression, the group of the higher hsa-miR-145 expression was significantly longer overall survival time compared to the lower expression group (P=0.0378).
Conclusion: The hsa-miR-145 may be potential prognostic factor for HCC patients.
Citation Format: Go Nakajima, Kazuhiko Hayashi. MicroRNA hsa-miR-145 expression in hepatocellular carcinoma correlates with patient survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4444. doi:10.1158/1538-7445.AM2017-4444
Abstract 4448A: MicroRNA profiling of prostate cancer tissue identifies a prognostic 4-miRNA model and implicates one novel microRNA in prostate cancer cell viability
Authors: Schmidt Linnea , Fredsøe Jacob , Kristensen Helle , Rasmussen Anne , Mouritzen Peter , Høyer Søren , Borre Michael , Ørntoft Torben , Sørensen Karina Dalsgaard 
Published: July 2017

Abstract
Purpose: New prognostic biomarkers for prostate cancer (PC) risk stratification are urgently needed. Here, we identify and validate a novel 4-microRNA prognostic ratio model for prostate cancer. We also identify a new microRNA with tumor suppressive characteristics in prostate cancer cell lines.
Methods: PC tissue samples from 123 radical prostatectomy (RP) patients, 58 of whom experienced biochemical recurrence, were profiled for genome-wide miRNA expression using RT-qPCR (training cohort). Initially, we identified 11 top candidate prognostic microRNAs (P &lt;0.05, univariate Cox regression). Based on these, all possible 2-4 microRNA ratio models were systematically tested for their potential to predict time to biochemical recurrence (BCR), as assessed by Kaplan-Meier, uni- and multivariate Cox regression analyses. The findings were validated in two independent RP cohorts. A novel microRNA, included in the final ratio model and with previously unknown function in prostate cancer, was over expressed using a microRNA mimic in PC3 and DU145 cells to evaluate its effect on prostate cancer cell viability and proliferation.
Results: We identified a new prognostic 4-microRNA ratio model ((miR-23a-3p*miR-10b-5p)/(miR-133a*miR-374b-5p)) that significantly predicted time to BCR independently of established clinicopathological variables in a training RP cohort (n=123). The ratio model was successfully validated in two independent RP cohorts including 112 and 476 patients, respectively. Ectopic expression of one of these microRNAs (miR-374b-5p) significantly inhibited viability and proliferation in two prostate cancer cell lines, suggesting it has a tumor suppressor function in PC.
Conclusions: Here, we describe the identification and independent validation of a 4-miRNA ratio model that allows risk stratifications of prostate cancer patients undergoing RP into different prognostic groups. Furthermore, we identify and functionally characterize a novel possible tumor suppressor miRNA in prostate cancer.
Citation Format: Linnea Schmidt, Jacob Fredsøe, Helle Kristensen, Anne Rasmussen, Peter Mouritzen, Søren Høyer, Michael Borre, Torben Ørntoft, Karina Dalsgaard Sørensen. MicroRNA profiling of prostate cancer tissue identifies a prognostic 4-miRNA model and implicates one novel microRNA in prostate cancer cell viability [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4448A. doi:10.1158/1538-7445.AM2017-4448A
Abstract 4450: The role of paired-like homeodomain 2B in non-small cell lung cancer progression
Authors: Lin Sheng-Yi , Huang Yu-Han , Lai Yi-Hua , Yu Sung-Liang , Su Sheng-Fang , Hong Tse-Ming , Chang Gee-Chen , Wang Chi-Chung , Chen Jeremy J.W. 
Published: July 2017

Abstract
The transcription factor PITX2 (paired-like homeodomain 2) is well known to play an essential role in normal embryonic development. Emerging evidence suggests that PITX2 may be involved in human tumorigenesis. However, the functional role that PITX2 plays in tumor progression remain unclear. In this study, we investigated its function in human non-small cell lung carcinoma (NSCLC). Using real-time quantitative RT-PCR, we demonstrated that PITX2B is the most abundant isoform in lung cancer cells. Enforced expression of PITX2B could promote lung cancer cell morphological change, migration, invasion, anchorage-dependent growth ability and tumorigenesis in xenograft model mice. In addition, nuclear PITX2B localization was correlated with its oncogenic functions and two important nuclear localization signals (NLSs) were identified. Moreover, high expression of PITX2B was associated with poor overall survival (P&lt;0.05) in NSCLC patients. Importantly, silencing of PITX2B by siRNA caused a marked increase in autophagy based on LC3-II, Beclin-1, and p62 protein expression, acridine orange fluorescence of acidic vacuoles and electron microscopic detection of autophagosomes. Furthermore, we found that the autophagy induced by PITX2B knockdown preceded apoptosis in lung cancer cells. Treatment of lysosome inhibitor, NH4Cl, could provide a protective effect that increases cell viability. In conclusion, our studies not only provide new insights into how PITX2B may contribute to the tumor progression in lung cancer but also the autophagy induced by PITX2B knockdown that may be developed as an effective therapeutic strategy for the treatment of lung cancer.
Citation Format: Sheng-Yi Lin, Yu-Han Huang, Yi-Hua Lai, Sung-Liang Yu, Sheng-Fang Su, Tse-Ming Hong, Gee-Chen Chang, Chi-Chung Wang, Jeremy J.W. Chen. The role of paired-like homeodomain 2B in non-small cell lung cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4450. doi:10.1158/1538-7445.AM2017-4450
Abstract 4451: Elevated USP22 is a potential therapeutic target for human non-small cell lung cancer
Authors: Zhang Keqiang , Tong Tommy R , Yun Xinwei , Nelson Rebecca , Isaac Nardi , Salgia Ravi , Raz Dan 
Published: July 2017

Abstract
Elevated ubiquitin-specific protease 22 (USP22) is associated with enhanced malignancy, therapeutic resistance, and poor prognosis of various human cancers. In this study, the clinicopathological significance of USP22, therapeutic implication of targeting USP22, and underlying molecules of USP22 knockdown were investigated in human non-small cell lung cancer (NSCLC). Immunohistochemistry analysis revealed that USP22 protein was dramatically elevated in ~ 67% of 197 NSCLC tissues compared with adjacent normal lung tissues. Importantly, statistical analysis demonstrated that elevated USP22 was positively associated with advanced cancer stage and a trend to poor prognosis of NSCLC patients. Moreover, siRNA-mediated knockdown of USP22 induced a cell cycle arrest in G1/S phase and significantly suppressed cell proliferation and soft agar colony formations in NSCLC cell lines. In addition, knockdown of USP22 significantly enhanced cisplatin-induced genotoxic effects in NSCLC cell lines. Furthermore, USP22 silencing substantially down-regulated SIRT1 and upregulated p53 tumor suppressor in NSCLC cells, indicating downregulation of USP22 may boost p53-mediated tumor suppression and DNA damage response in NSCLC cells. Knockdown of USP22 also increased global histone H2B monoubiquitylation, H3K4 and H3K79 trimethylation leading to global gene expression profile changes in these NSCLC cells. These results suggest that targeting USP22 will have broad anti-cancer effects via altering multiple cancer signaling pathways. Taken together, data of this study further indicate that the elevated USP22 may potentially represent a prognostic factor and therapeutic target for NSCLC patients.
Note: This abstract was not presented at the meeting.
Citation Format: Keqiang Zhang, Tommy R Tong, Xinwei Yun, Rebecca Nelson, Nardi Isaac, Ravi Salgia, Dan Raz. Elevated USP22 is a potential therapeutic target for human non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4451. doi:10.1158/1538-7445.AM2017-4451
Abstract 4452: Study of the mechanisms of emetine dihydrochloride on inhibiting NSCLC tumor progression and attenuating EGFR signaling pathway
Authors: Lai Yi-Hua , Huang Wan-Ting , Lin Sheng-Yi , Huang Yao-Ting , Chen Yuh-Ling , Chen Hsuan-Yu , Chen Huei-Wen , Chen Jeremy J.W. 
Published: July 2017

Abstract
Epidermal growth factor receptor (EGFR) is a transmembrane receptor protein and can mediate the cellular biological responses including regulation of cellular proliferation, differentiation, migration and survival. More than 60 % of non-small cell Lung cancers (NSCLCs) express relatively high level of EGFR. Therefore, EGFR has become an important therapeutic target for the treatment of NSCLC. However, almost all NSCLC patients ultimately develop drug resistance to targeted therapy agents. The most common secondary mutation is found to harbor EGFR mutation in T790M, which is acquired resistance to EGFR TKIs. In order to overcome the resistance of T790M mutation in lung cancer, we used EGFR pY1068 ELISA as drug-screening platform to screen the candidate compounds with the capacity to suppress EGFR activity from the compound library of more than 300 plant active ingredients. Among the compounds identified, the emetine could most significantly restrain EGFR pY1068 activity and reduce cancer cell viability. Moreover, the Western blotting results showed that emetine treatment can repress EGFR phosphorylation and expression in a dose-dependent manner as well as inhibit its downstream substrates including PI3K, STAT3 and Src in three different Iressa-resistant cell lines. In addition, emetine also could inhibit cell proliferation, migration, invasion, and clonogenicity in vitro and xenograft tumor growth in vivo. Taken together, our data suggest that emetine might be a novel inhibitory modulator of EGFR activity and might be through suppressing the phosphorylation and expression of PI3K, STAT3, and Src to inhibit lung cancer progression. These findings will help us to develop the anti-cancer drugs for lung cancer in the future.
Citation Format: Yi-Hua Lai, Wan-Ting Huang, Sheng-Yi Lin, Yao-Ting Huang, Yuh-Ling Chen, Hsuan-Yu Chen, Huei-Wen Chen, Jeremy J.W. Chen. Study of the mechanisms of emetine dihydrochloride on inhibiting NSCLC tumor progression and attenuating EGFR signaling pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4452. doi:10.1158/1538-7445.AM2017-4452
Abstract 4459: Glycine decarboxylase inhibits proliferation of ovarian cancer cells via SIRT1-mediated apoptosis
Authors: Shin So-Jin , Kim Jin-Young , Ha Eun-Young , Cho Chi-Heum 
Published: July 2017

Abstract
Glycine decarboxylase (GLDC) is a very recently identified metabolic oncogene that links glycine metabolism with tumorigenesis. We designed this study to determine the mechanistic role of GLDC in in ovarian cancer cells. First, we confirmed the expressions of GLDC in eight different ovarian cancer cell lines. And colony formation assay revealed decreased proliferation of OVCAR3 ovarian cancer cells transfected with siGLDC compared with that of control. Intriguingly, we found that knockdown of GLDC induced decreased S-adenosylmethionine (SAM)/ S-adenosylhomocysteine (SAH) ratio, which implicates methyl donor deficient state in OVCAR3 cells. Expressions of sirtuin 1 (SIRT1), heat shock protein (HSP) 90 and heat-shock factor protein 1 (HSF1) decreased while that of p53 increased in GLDC knock-downed cells, suggesting heat shock response. Addition of SAM into siGLDC knock-downed cell restored the expression of SIRT1. Inhibition of SIRT1 decreased Bcl2 and increased cytochrome c expressions. In summary, these results suggest GLDC induces methyl donor deficient state in OVCAR3 ovarian cancer cells, which in turn leads to apoptosis via SIRT1-mediated pathway.
Citation Format: So-Jin Shin, Jin-Young Kim, Eun-Young Ha, Chi-Heum Cho. Glycine decarboxylase inhibits proliferation of ovarian cancer cells via SIRT1-mediated apoptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4459. doi:10.1158/1538-7445.AM2017-4459