bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1057: Bioluminescent assays for investigating cellular energy metabolism
Authors: Leippe Donna M. , Sobol Mary , Valley Mike , Karassina Natasha , Duellman Sarah , Vidugiriene Jolanta , Cali Jim 
Published: July 2016

Abstract
Cellular energy metabolism is recognized to have a central role in many cell processes and is an increasingly important area of study in many research fields such as cancer, immunology, obesity, diabetes and neurology. To facilitate these studies, we have taken advantage of key features of bioluminescence, such as increased sensitivity and wide assay windows, to develop assays for measuring energy metabolites. These assays are easy-to-use plate-based assays with streamlined protocols that require minimal cell sample processing. The assays can be used to measure consumption of major fuel sources such as glucose and glutamine from the cell medium, as well as lactate and glutamate secretion. The sensitivity (1-5pmol/sample), broad linear range (0.1-100 uM) and wide dynamic range (maximum signal-to-background &gt; 100 fold) allow all four metabolites to be measured from the same sample of medium and over time, with earlier detection from fewer cells compared to other methods. The assays are also sensitive enough to detect intracellular levels of glutamine, glutamate and lactate and changes in those levels. Additional assays have been developed to measure glucose uptake and NAD/NADH levels in cells. Analysis of these metabolites provides information regarding the energetic state of the cell. In this poster we provide examples demonstrating the utility of these assays to detect a glycolytic shift in cancer cells, monitor cell growth and differentiation with associated changes in glucose uptake and glycolysis, and evaluate insulin sensitivity in primary adipocytes.
Citation Format: Donna M. Leippe, Mary Sobol, Mike Valley, Natasha Karassina, Sarah Duellman, Jolanta Vidugiriene, Jim Cali. Bioluminescent assays for investigating cellular energy metabolism. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1057.
Abstract 1060: Targeting serine hydroxymethyltransferase 2 (SHMT2) suppresses hepatocarcinoma
Authors: Woo Chern Chiuh , Chen Way Cherng , Philip Lee. Teck Hock 
Published: July 2016

Abstract
Glycolytic intermediate 3-phosphoglycerate branched from glycolysis pathway to fuel serine-glycine biosynthesis pathway. Several studies have shown that glycine consumption is strongly correlated to the proliferation rate of cancer cells. Therefore targeting serine-glycine biosynthesis pathway is a promising strategy due to the fact that many of its genes are up-regulated in cancer cells. These genes include PHGDH, PSAT1 and GLDC. Here, we demonstrate that targeting serine hydroxymethyltransferase 2 (SHMT2), also a member of serine-glycine biosynthesis pathway, is able to suppress hepatocarcinoma both in vitro and in vivo. SHMT2 simultaneously converts serine to glycine and tetrahydrofolate to 5,10-methylenetetrahydrofolate. We found that this gene is up-regulated in Hep3B, HepG2 and Huh-7 liver cancer cells versus THLE2 normal liver cells. Knockdown of SHMT2 effectively suppressed Huh-7 cell growth and tumorigenicity. No tumor was formed after inoculation of SHMT2-knockdown Huh-7 cells in nude mice as compared to 100% tumor formation with control Huh-7 cells. The data from tetracycline-inducible SHMT2-knockdown xenograft mouse model showed that SHMT2 inhibition could reduce tumor growth and tumor incidence as well as delayed tumor onset. We also found that SHMT2-knockdown Huh-7 cells were more vulnerable to the cytotoxicity of doxorubicin, a conventional chemotherapeutic agent, as compared to the control Huh-7 cells. On the other hand, overexpression of SHMT2, however, could not transform THLE2 cells into malignancy suggesting that SHMT2 might not a key driver in liver tumorigenesis. SHMT2 activity is correlated to cancer phenotype as shown by the NMR data via metabolic tracing with 13C-glycine. Supplementation of glycine, rather than 5,10-methylenetetrahydrofolate, could reverse the reduced tumorigenicity caused by SHMT2-knockdown. Taken together, our data support that SHMT2 is a potential target in the treatment of hepatocarcinoma.
Citation Format: Chern Chiuh Woo, Way Cherng Chen, Teck Hock Philip Lee. Targeting serine hydroxymethyltransferase 2 (SHMT2) suppresses hepatocarcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1060.
Abstract 1085: Serum miR-30e and miR-223 are promising non-invasive biomarkers for hepatocellular carcinoma
Authors: Ray Ratna B. , Bhattacharya Sourav , Steele Robert , Di Bisceglie Adrian M. , chakraborty Sounak 
Published: July 2016

Abstract
Hepatocellular carcinoma (HCC) is the world's third most common cancer and causes 600,000 deaths annually. Early detection is the key for improving the survival of HCC patients. Current diagnostic markers, such as alpha fetoprotein or fibroscan have their own limitations. Investigating serum microRNA as biomarkers for early diagnosis of cancer has become an important tool in clinical research. In this study, we tested the hypothesis that serum microRNAs (miRNAs) can be used as a potential biomarker for HCC. We analyzed serum miRNA using reverse transcriptase-quantitative PCR (qRT-PCR) from serum samples. Our study revealed that two miRNAs, miR-30e and miR-223, were expressed at significantly lower levels (P &lt; 0.003) in the sera of HCC patients as compared to healthy volunteers. Further, expression of these miRNA was compared between sera from chronic liver disease (CLD) and HCC patients. miR-30e and miR-223 expression was significantly lower in HCC sera as compared to sera from CLD patients. Both miRNA expression levels were lower in HCC liver biopsy specimens as compared to normal liver RNA. Taken together, our results indicated that serum miR-30e and miR-223 are useful biomarkers of HCC irrespective of etiology.
Citation Format: Ratna B. Ray, Sourav Bhattacharya, Robert Steele, Adrian M. Di Bisceglie, Sounak chakraborty. Serum miR-30e and miR-223 are promising non-invasive biomarkers for hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1085.
Abstract 1095: S100A4 is post-transcriptionally inhibited by miR-505-5p and miR-520c-3p in colorectal cancer
Authors: Mudduluru Giridhar , Ilm Katharina , Fuchs Steffen , Stein Ulrike 
Published: July 2016

Abstract
The calcium binding protein S100A4 induces epithelial mesenchymal transition (EMT), migration, invasion, angiogenesis and metastasis. Its induced expression is reported in several cancer types and correlates with poor prognosis. S100A4 is transcriptionally regulated by Sp1, AP1 and CCAAT/enhancer binding protein β transcription factors and its regulation epigenetically controlled by CpG hyper methylation. However, apart from S100A4 functional and transcriptional regulatory aspects, post-transcriptional regulation is not yet elucidated. In this study, we show that specific microRNAs (miR) target the 3’UTR of S100A4. Luciferase-reporter assays with wild-type and mutated miR-505-5p and miR-520c-3p seed sequences of S100A4-3’UTR confirmed the specificity of targeting. Similarly, overexpression of these miRs reduced the S100A4 and inhibition of these miRs function increased the S100A4 protein significantly. Moreover, co-transfection of either S100A4 expressing vector or siRNA-S100A4 along with the miR-505-5p and miR-520c-3p significantly altered the S100A4 mediated migration and invasion in colorectal cancer (CRC) cell lines (p = 0.05). Both these miRs were down-regulated in CRC cell lines and 5 Aza treatment increased these miRs expression and reduced the S100A4 protein amounts. Moreover, in a panel of CRC resected patient tissues (n = 59), miR-520c-3p significantly down regulated (p = 0.03). miR-520c (located in Chr 19, in a big cluster) upstream region was checked for methylation status using methylation specific PCR and combined bisulfite restriction analysis (COBRA) in CRC cell lines, metastatic and non-metastatic CRC resected tissues. We found the upstream promoter region hyper methylated irrespective of metastasis status of patients and in all CRC cell lines checked. 5 Aza treatment of S100A4 less or no expressing cells line Colo206 and Colo320 showed induced miR-520c expression and reduced S100A4 protein in Colo320. Colo206 cells did not show any alternations in expression of S100A4. Taken together, our findings demonstrate that S100A4 is post-transcriptionally regulated by tumor suppressor genes miR-505c and miR-520c and especially miR-520c expression is epigenetically silenced in CRC.
Citation Format: Giridhar Mudduluru, Katharina Ilm, Steffen Fuchs, Ulrike Stein. S100A4 is post-transcriptionally inhibited by miR-505-5p and miR-520c-3p in colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1095.
Abstract 1099: Up-regulated miR-96-5p inhibits apoptosis by targeting FOXO1 in hepatocellular carcinoma
Authors: Iwai Naoto , Yasui Kohichiroh , Tomie Akira , Kitaichi Tomoko , Dohi Osamu , Gen Yasuyuki , Itoh Yoshito 
Published: July 2016

Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers and the third leading cause of cancer death worldwide, especially in Asia and sub-Saharan Africa. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and can act as tumor suppressors or oncogenes. To identify miRNA involved in HCC, we performed a genome-wide miRNA gene expression analysis using the human miRNA microarray (Agilent) in paired tumor and non-tumor tissues from patients with primary HCC. The array-based miRNA expression profiles were validated by quantitative PCR. We identified miR-96-5p as the most significantly upregulated miRNA in HCC tumors. Although miR-96-5p has been recognized as an oncogenic miRNA, its role in the pathogenesis of HCC remains unknown. Our study showed that the inhibition of miR-96-5p reduced proliferation of HCC cells and induced apoptosis. Furthermore, we found that the forkhead box O1 (FOXO1) gene was a target of miR-96-5p. FOXO1, a transcription factor, plays an essential role in cell fate decisions. FOXO1 can induce apoptosis through mitochondria-dependent and mitochondria-independent pathways. Collectively, our results suggested that miR-96-5p may function as an oncogenic miRNA through inhibiting apoptosis by targeting FOXO1 in HCC.
Citation Format: Naoto Iwai, Kohichiroh Yasui, Akira Tomie, Tomoko Kitaichi, Osamu Dohi, Yasuyuki Gen, Yoshito Itoh. Up-regulated miR-96-5p inhibits apoptosis by targeting FOXO1 in hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1099.
Abstract 110: Molecular profiling of Tudor domain-containing proteins identifies PHF20L1 as a candidate oncogene in breast cancer
Authors: Jiang Yuanyuan , Liu Lanxin , Shan Wenqi , Yang Zeng-Quan 
Published: July 2016

Abstract
Tudor domain-containing proteins (TDRDs), which recognize and bind to methyl-lysine/arginine residues on histones and non-histone proteins, play critical roles in regulating chromatin architecture, transcription, genomic stability, and RNA metabolism. Dysregulation of several TDRDs have been observed in various types of cancer. However, neither the genomic landscape nor clinical significance of TDRDs in breast cancer has been explored comprehensively. Here, we performed an integrated genomic and transcriptomic analysis of 41 TDRD genes in breast cancer (TCGA and METABRIC datasets) and identified associations among recurrent copy number alterations, gene expressions, clinicopathological features, and survival of patients. Among seven TDRDs (PHF20L1, ARID4B, SETDB1, LBR, TDRKH, TDRD10, and TDRD5) that had the highest frequency (&gt;10%) of gene amplification, the plant homeodomain finger protein 20-like 1 (PHF20L1) was the most commonly amplified (17.62%) TDRD gene in TCGA breast cancers. Different subtypes of breast cancer had different patterns of copy number and expression for each TDRD. Notably, amplification and overexpression of PHF20L1 were more prevalent in aggressive basal-like and Luminal B subtypes and were significantly associated with shorter survival of breast cancer patients. Furthermore, knockdown of PHF20L1 inhibited cell proliferation in PHF20L1-amplified breast cancer cell lines. PHF20L1 protein contains N-terminal Tudor and C-terminal plant homeodomain domains. Detailed characterization of PHF20L1 in breast cancer revealed that the Tudor domain likely plays a critical role in promoting cancer. Mechanistically, PHF20L1 might participate in regulating DNA methylation by stabilizing DNA methyltransferase 1 (DNMT1) protein in breast cancer. Thus, our results demonstrated the oncogenic potential of PHF20L1 and its association with poor prognostic parameters in breast cancer. Furthermore, our findings provide strong foundations for further research and therapeutic targeting of PHF20L1 or other TDRDs in breast cancer.
Citation Format: Yuanyuan Jiang, Lanxin Liu, Wenqi Shan, Zeng-Quan Yang. Molecular profiling of Tudor domain-containing proteins identifies PHF20L1 as a candidate oncogene in breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 110.
Abstract 1101: The role of miR-601 in prostate cancer progression
Authors: Fleming Jessica L. , Hlavin Bell Erica , Andrews Kathryn , Chakravarti Arnab 
Published: July 2016

Abstract
Prostate cancer (PCa) is the second most common cancer among men worldwide. In order to advance treatment options for these men, it is crucial to understand the molecular underpinning behind this cancer. Previously, our group identified miR-601 as a predictive biomarker in PCa. Few studies to date have functionally validated molecular biomarkers and currently nothing is known about the function of miR-601 in PCa. Based on our previous publication, we hypothesized that miR-601 is playing a role in PCa progression. In order to assess this, in vitro experiments were conducted in three PCa cell lines, DU-145, PC-3, and LNCaP. miR-601 was over-expressed and knocked down in each cell line and assays were performed evaluating cell proliferation, colony formation, and apoptosis. Additionally, to provide more information regarding miR-601-associated pathways, we identified putative gene targets of miR-601 using in silico prediction programs, microrna.org and TargetScan.org and evaluated top gene targets in vitro. The results of our experiments indicate that miR-601 is playing a role of a tumor suppressor. Over-expression of miR-601 in cell lines resulted in a significant reduction in cell viability. This was confirmed both by MTS as well as colony formation assays. We looked into the mechanism behind the reduction in cell viability and found that cells over-expressing miR-601 had reduced levels of full-length caspase-3, signifying that these cells are undergoing apoptosis. Two putative gene targets of miR-601 were identified and investigated in vitro, SIRT1, a histone deacetylase known to be both an oncogene and tumor suppressor, and BCL2L2, an anti-apoptotic gene known to be an oncogene. SIRT1 and BCL2L2 had strong scores on both online prediction programs as likely targets of miR-601. Our in vitro results confirmed this. We saw reduced mRNA and protein expression of these targets in cells over-expressing miR-601. Our data thus far suggest that miR-601 is acting as a tumor suppressor in PCa. Targeted therapies for miR-601 and/or its targets may be promising in the treatment of PCa, however additional work is needed to warrant this.
This work was supported by R01CA108633 (To AC), 1RC2CA148190 (To AC) U10CA180850-01 (To AC), 1R01CA169368 (To AC) from the National Cancer Institute (NCI), Brain Tumor Funders Collaborative Grant (To AC), Ohio State University Comprehensive Cancer Center Award (To AC).
Citation Format: Jessica L. Fleming, Erica Hlavin Bell, Kathryn Andrews, Arnab Chakravarti. The role of miR-601 in prostate cancer progression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1101.
Abstract 1106: Mir-223-5p works as an oncomir in vulvar carcinoma by TP63 regulation
Authors: Rocha Rafael , De Melo Maia Beatriz , Rodrigues Iara S. , Amaral Nayra S. , Ling Hui , Calin George A. , Soares Fernando A. 
Published: July 2016

Abstract
Recently, miR-223-5p was associated with metastasis in HPV negative vulvar samples and in several other tumor types. In the present study, we hypothesized that this microRNA would have a potential impact on in vitro vulvar cancer behavior. We artificially mimicked microRNA expression in vulvar cancer cell line, SW962, derived from lymph node metastasis of vulvar carcinoma, and performed in vitro assays as follows in the result section. Impaired cell proliferation (p&lt;0.01) and migration (p&lt;0.001) were observed when miR-223-5p was overexpressed. In contrast, increased invasive potential of the cells was observed (p&lt;0.004). By Luciferase assay we provide evidence that miR-223-5p targets TP63 through its 3’UTR direct ligation (p&lt;0.05). We also demonstrate that this microRNA is capable to decrease levels of p63 at both mRNA and protein levels (p&lt;0.001, and p&lt;0.0001; respectively). We further demonstrated that low p63 protein expression in samples from patients was correlated with deeper tumor (p&lt;0.0345) invasion and lower overall survival (p&lt;0.0494). Our study highlights the complexity surrounding p63 biological mechanisms and the importance of this protein as a prognostic factor in vulvar cancer. We also point out miR-223-5p overexpression as a putative pathological mechanism of tumor invasion and a promising therapeutic target. Also, it is plausible that the evaluation of p63 expression in vulvar cancer at the biopsy level may bring important contribution on prognostic establishment and in elaborating better surgical approaches for vulvar cancer patients.
Citation Format: Rafael Rocha, Beatriz De Melo Maia, Iara S. Rodrigues, Nayra S. Amaral, Hui Ling, George A. Calin, Fernando A. Soares. Mir-223-5p works as an oncomir in vulvar carcinoma by TP63 regulation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1106.
Abstract 1107: miR-29b acts as an oncogene or tumor suppressor gene depending on the external stimulus
Authors: Vassella Erik , Langsch Stephanie 
Published: July 2016

Abstract
microRNAs (miRNAs), short regulatory sequences at the posttranscriptional level, are important mediators of signaling pathways that act as backups of transcriptional control. To identify miRNAs implicated in epidermal growth factor receptor (EGFR) signaling, transformed bronchial epithelial BEAS-2B cells were retrovirally transduced with KRASG12V and alterations in miRNA expression were assessed by microarray analysis. Here we show that miR-29b is significantly induced by mutant KRAS in bronchial epithelial and non-small cell lung cancer (NSCLC) cell lines as well as in primary NSCLC tissue. In agreement with these results, inhibitors of EGFR and MEK resulted in reduced levels of miR-29b while inhibitors of PI3K had no effect. KRASG12V-transduced BEAS-2B cells were significantly more protected from extrinsic apoptosis than control transduced cells, but co-transduction of cells with KRASG12V and anti-miR-29b constructs sensitized cells to apoptosis indicating that miR-29b is a mediator of KRAS-induced resistance to apoptosis. Protection from extrinsic apoptosis was due to enhanced nuclear factor κB (NF-κB) activity. The ubiquitin-editing enzyme tumor necrosis factor alpha-induced protein 3 (TNFAIP3/A20) is a negative regulator of NF-κB signaling. Enhanced NF-κB activity elicited by miR-29b was due to targeting TNFAIP3/A20. Overexpression of miR-29b-refractory TNFAIP3 restored NF-κB activity as well as extrinsic apoptosis, demonstrating that TNFAIP3 is a relevant target of miR-29b. Interestingly, miR-29b conferred sensitivity to cisplatin-induced intrinsic apoptosis by targeting Mcl-1. Thus, miR-29b tips the balance from extrinsic apoptosis towards intrinsic apoptosis. Our results indicate that miR-29b can act either as an oncogene or tumor suppressor gene depending on the external stimulus.
Citation Format: Erik Vassella, Stephanie Langsch. miR-29b acts as an oncogene or tumor suppressor gene depending on the external stimulus. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1107.
Abstract 1108: MicroRNA-211 enhances the oncogenicity of oral carcinoma through targeting TCF12 and up-regulating FAM213A expression
Authors: Chen Yi-Fen , Chang Kuo-Wei , Lin Shu-Chun 
Published: July 2016

Abstract
To address the oncogenic roles of miR-211, we generated K14-EGFP-miR-211 transgenic mouse lines. Upon the 4-nitroquinoline 1-oxide (4NQO) induction, the transgenic mice exhibited more extensive and severe tumorigenesis in tongue compared to the controls. 4NQO up-regulated miR-211 expression in oral squamous cell carcinoma (OSCC) cells. miR-211 directly targeted transcription factor 12 (TCF12), which mediated suppressor activities and was drastically down-regulated in OSCC tumors. GeneChip analysis, bioinformatic algorithm, reporter assay and ChIP assay pinpointed that Family with Sequence Similarity 213, Member A (FAM213A), an anti-oxidative molecule, was transcriptionally repressed by TCF12. Knockdown of FAM213A decreased oncogenic activity and ALDH1-positive cell population, and increased oxygen stress in OSCC cells. The expression of TCF12 and FAM213A was inversely correlated in head and neck carcinoma samples according to The Cancer Genome Atlas. OSCC patients carrying tumors with high FAM213A expression tended to have worse survival. Furthermore, 4NQO treatment down-regulated TCF12 and up-regulated FAM213A through modulating miR-211. The transgenic mouse model recaptures the molecular and histopathological changes as seen in human OSCC pathogenesis. This study highlights that miR-211 responds to oncogenic stimuli to promote the neoplastic process of OSCC by targeting TCF12 and up-regulating FAM213A.
Citation Format: Yi-Fen Chen, Kuo-Wei Chang, Shu-Chun Lin. MicroRNA-211 enhances the oncogenicity of oral carcinoma through targeting TCF12 and up-regulating FAM213A expression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1108.