bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 884: NSD3-short is an adaptor protein that couples BRD4 to the CHD8 chromatin remodeler
Authors: Shen Chen , Ipsaro Jonathan J. , Shi Junwei , Vakoc Christopher R. 
Published: July 2016

Abstract
The bromodomain and extraterminal (BET) protein BRD4 is a therapeutic target in acute myeloid leukemia (AML). Here, we demonstrate that the AML maintenance function of BRD4 requires its interaction with NSD3, which belongs to a subfamily of H3K36 methyltransferases. Unexpectedly, AML cells were found to only require a short isoform of NSD3 that lacks the methyltransferase domain. We show that NSD3-short is an adaptor protein that sustains leukemia by linking BRD4 to the CHD8 chromatin remodeler, by utilizing a PWWP chromatin reader module, and by employing an acidic transactivation domain. Genetic targeting of NSD3 or CHD8 mimics the phenotypic and transcriptional effects of BRD4 inhibition. Furthermore, BRD4, NSD3, and CHD8 colocalize across the AML genome and are each released from super-enhancer regions upon chemical inhibition of BET bromodomains. These findings suggest that BET inhibitors exert therapeutic effects in leukemia by evicting BRD4-NSD3-CHD8 complexes from chromatin to suppress transcription.
Citation Format: Chen Shen, Jonathan J. Ipsaro, Junwei Shi, Christopher R. Vakoc. NSD3-short is an adaptor protein that couples BRD4 to the CHD8 chromatin remodeler. [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 884.
Abstract 904: Heterozygous ATG7 inhibition enhances endocrine therapy responsiveness through regulation of damage associated molecular patterns and priming the immune system in ER+ breast tumors
Authors: Clarke Robert , Clarke Pamela A.G. , Wärri Anni , Cook Katherine L. 
Published: July 2016

Abstract
Breast cancer is the most prevalent cancer in women, with over 230,000 new cases diagnosed annually. The most common type of breast cancer, comprising over 70% of all cases, express the estrogen receptor (ER); these tumors are usually treated with an endocrine therapy such as an antiestrogen or aromatase inhibitor. Unfortunately, many of these tumors develop resistance, or in some instances express de novo resistance, which limits the curative potential of these therapies. Autophagy, a cellular process of “self-eating”, is implicated as possible contributor to endocrine therapy resistance in breast cancer. We previously showed that inhibiting autophagy through low-dose chloroquine treatment reversed antiestrogen therapy resistance in ER+ orthotopic breast tumors. We now show that heterozygous deletion of ATG7 decreased breast tumor multiplicity and increased endocrine targeting therapy sensitivity in a DMBA-model of ER+ mammary carcinogenesis. Knockdown of ATG7 through RNAi increased cytoplasmic to nuclear high-mobility group binding protein B1 (HMGB1) protein ratio, suggesting targeting ATG7 promotes damage associated molecular patterns (DAMP) signaling. Heterozygous deletion of ATG7 also increased cytoplasmic HMGB1 protein expression in tumor epithelial cells indicating targeting ATG7 promotes DAMP signaling in vivo. Furthermore, tumors from ATG7 heterozygous mice displayed increased CD68 staining indicating elevated macrophage infiltration. Corroborating previous literature showing the critical role of autophagy in T-cell maturation, splenic CD8+ T-cells were significantly reduced in tumor bearing ATG7 heterozygous mice. However, ATG7 heterozygous mice displayed increased tumor CD8+ T-cell population. These data suggest that while targeting ATG7 reduces overall circulating T-cell populations, inhibiting ATG7 enhances tumoral cytotoxic T-cell recruitment. Tumors from ATG7 heterozygous mice also showed a significant decrease in foxp3+ cells, indicating targeting ATG7 reduces immuno-suppressive T-reg population. Serum from ATG7 heterozygous mice showed increased circulating MDC, MCP-1, IL-6, and eotaxin cytokines. Taken together, these data suggests that ATG7 inhibition promotes an anti-tumor pro-inflammatory cytokine profile to enhance tumoral immune cell recruitment and promote endocrine therapy responsiveness.
Citation Format: Robert Clarke, Pamela A.G. Clarke, Anni Wärri, Katherine L. Cook. Heterozygous ATG7 inhibition enhances endocrine therapy responsiveness through regulation of damage associated molecular patterns and priming the immune system in ER+ breast tumors. [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 904.
Abstract 962: Deregulated transcription of mouse satellite sequences accelerates oncogenic processes via functional inhibition of YBX1 protein
Authors: Kishikawa Takahiro , Otsuka Motoyuki , Koike Kazuhiko 
Published: July 2016

Abstract
Highly repetitive tandem arrays located at centromere and pericentromere regions of the chromosomes had been considered epigenetically silent by heterochromatin modification. However, the deregulated transcription of the non-coding satellite sequences exists in human and mouse pancreatic cancer tissues. This aberrant expression can be detected even in Kras-mutated pancreatic intraepithelial neoplasia (PanIN) tissues, which are pre-cancerous lesions to invasive pancreatic cancer. To examine the biological roles of these aberrantly expressed satellite RNAs during the carcinogenesis steps, we established genetically-modified mouse PanIN-derived cells, in which mouse major satellite (MajSAT) RNAs were ectopically expressed. MajSAT RNA expressing PanIN-derived cells showed the increased chromosomal instability and the rate of spontaneous point mutations in the genomic as well as in the mitochondrial DNAs. We identified YBX1 protein as a binding protein specifically with MajSAT RNA by RNA immunoprecipitation. MajSAT RNA inhibited nuclear translocation of YBX1 under oxidative damage, which reduced the DNA damage repair activity of YBX1. The mutation rate of genomic and mitochondrial DNAs, and transformation rate were rescued by YBX1 overexpression in these cells. These findings indicate that satellite transcripts at the early stage of cancer development may act as “mutagens” and accelerate oncogenic processes.
Citation Format: Takahiro Kishikawa, Motoyuki Otsuka, Kazuhiko Koike. Deregulated transcription of mouse satellite sequences accelerates oncogenic processes via functional inhibition of YBX1 protein. [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 962.
Abstract 964: Circulating biomarker miRNA-150 promotes tumor cell proliferation and progression by targeting SRC kinase signaling inhibitor 1 (SRCIN1) in non-small cell lung cancer
Authors: Lin Jing , Zhang Liren , Ye Yuanqing , Oba Taro , Gentile Emanuela , Gentile Emanuela , Wang Jing , Zhao Yang , Gu Jian , Wistuba Ignacio , Roth Jack A. , Wu Xifeng , Ji Lin 
Published: July 2016

Abstract
Circulating microRNAs (c-miRNAs) expression ratio (ER) signatures were evaluated as prognostic biomarkers and therapeutic targets in early stage non-small cell lung cancer (NSCLC) patients. In a population study with 171 stage I and II NSCLC patients, the miR-150 and associated ER signature miR27A/miR-150 (ER ≥0.86, HR = 3.92, p = 1.46E-4) were significantly associated with 5-year survival. The upregulated expression of miR-150 was detected in primary tissue samples (n = 245) by miRNA microarray profiling analysis and significantly associated with cancer recurrence (p = 0.027) and overall survival (HR = 0.88, p = 0.04). Ectopic expression of miR-150 in NSCLC H1299, A549, and H2023 cells transfected by miR-150 expression plasmids promoted tumor cell proliferation, tumor cell-induced colony formation and migration/invasion, while blocking the action of miR-150 with a synthetic miR-150 inhibitor or transduction with a miRZip-150 inhibitor expressed by a lentiviral vector significantly inhibited these biological activities. The SRC kinase signaling inhibitor 1 (SRCIN1) was predicted to be a potential target of miR-150 by bioinformatics tools.miR-150-targeted binding and cleavage in the 3’-UTR of SRCIN1 mRNA were confirmed by a novel stem-loop array-reverse transcription-PCR assay. Both SRCIN1 gene and protein expression were significantly downregulated by ectopic expression of miR-150 and upregulated by miR-150 inhibitors in H1299 and H2023 NSCLC cells, as demonstrated by qRT-PCR and Western-blotting assays, respectively. Modulation of key elements in the SRCIN1 signaling pathway by ectopic expression or inhibition of miR-150 were further determined by qRT-PCR and predicted by ingenuity pathway analysis. Our findings suggest that circulating miR-150 and its associated ER signatures could serve as novel prognostic biomarkers for early stage NSCLC and function as an oncogenic miRNA that promotes lung cancer cell proliferation, invasion, and metastasis by direct targeting SRCIN1signaling pathway thus identifying SRCIN1 as a potential therapeutic target.
Citation Format: Jing Lin, Liren Zhang, Yuanqing Ye, Taro Oba, Emanuela Gentile, Emanuela Gentile, Jing Wang, Yang Zhao, Jian Gu, Ignacio Wistuba, Jack A. Roth, Xifeng Wu, Lin Ji. Circulating biomarker miRNA-150 promotes tumor cell proliferation and progression by targeting SRC kinase signaling inhibitor 1 (SRCIN1) in non-small cell lung 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 964.
Abstract 97: A novel PTPRK-FILIP1 fusion gene in invasive mucinous adenocarcinoma of lung without known driver mutations
Authors: Hong Sung-Hye , Lee Geon Kook , Song Sang Hoon , Lee Seung Youn , Kim Jin Young , Han Ji-Youn 
Published: July 2016

Abstract
Invasive mucinous adenocarcinoma (IMA) accounts for 2 to 10% of all adenocarcinoma cases of the lung and has a poor prognosis. The KRAS mutation is the most commonly detected genetic alteration in IMAs. Recent progress has permitted the identification of novel fusions such as NRG1. In an effort to further discovery of new driver oncogenes, we have carried out whole-transcriptome sequencing of IMA. To exclude IMA cases with known driver oncogenes, we performed targeted sequencing using the Ion AmpliSeq Cancer Hotspot Panel. We also tested other currently known fusion genes in lung cancer including CD74-NRG1, TPM3-ROS1, SDC4-ROS1, SLC34A2-ROS1, CD74-ROS1, EZR-ROS1, LRIG-ROS1, KIF5B-RET, CCDC6-RET1, EZR-ERBB4, TRIM24-BRAF, KIAA1468-RET, EML4-ALK, and KIF5B-ALK using RT-PCR. Finally we found 10 IMA cases without known driver oncogenes and performed transcriptome paired-end sequencing (the Illumina HiSeq platform). We utilized and compared 3 bioinformatic pipelines, FusionMap, deFuse, and ChimeraScan to identify fusion events. Of 10 IMA cases tested, we found 2 novel fusions, PTPRK-FILIP1 and CEP85L-RNGTT, from a never-smoking female patient. They were shared across all three fusion-finder and never reported in TCGA fusion gene data portal. Only PTPRK-FILIP1 was showed an in-frame fusion between exon 2 of PTPRK and 5’ UTR of FILIP1. It was confirmed by RT-PCR analysis and Sanger sequencing. This precise fusion was not present in the matched normal tissue. The reading frame is preserved that both the start codon of PTPRK and FILIP1. However, PTPRK mRNA expression is increased until exon 2 because of the fusion includes only two exons of PTPRK. Otherwise, expression analysis showed significant increase of FILIP1 mRNA expression in the affected tumor pair sample. The protein product from FILIP1 is closely associated with the protein filamin A, which is associated with tumor proliferation, cell migration, and metastasis. Many studies have reported that filamin A as a poor prognostic factor. Considering its implication in tumor proliferation, cell migration, and metastasis, PTPRK-FILIP1 could be a novel target for IMA. This is the first report of PTPRK-FILIP1 fusion gene in IMA without known driver mutations. Further functional validation of FILIP1 fusion is planned.
Citation Format: Sung-Hye Hong, Geon Kook Lee, Sang Hoon Song, Seung Youn Lee, Jin Young Kim, Ji-Youn Han. A novel PTPRK-FILIP1 fusion gene in invasive mucinous adenocarcinoma of lung without known driver mutations. [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 97.
Abstract 971: A novel long noncoding RNA, onco-lncRNA 230, induces apoptosis and invasion in lung squamous cell carcinoma
Authors: Tang Cynthia Y. , Silva-Fisher Jessica M. , Dang Ha X. , White Nicole M. , Maher Christopher A. 
Published: July 2016

Abstract
Long non-coding RNAs (lncRNAs) are RNAs that are longer than 200 base pairs and do not translate into proteins but have been shown to play roles in all aspects of biological regulation. LncRNAs have also been shown to regulate gene expression including chromatin organization, transcriptional regulation, and post-transcriptional control. In addition, they are now emerging to be important players in our understanding of cancer and have been shown to promote tumorigenesis. However, the mechanisms driving the advancement of tumor progression to metastasis is poorly understood. To identify lncRNAs critical to tumorigenesis, our lab conducted a pan-cancer analysis of normal and primary tumor tissues from The Cancer Genome Atlas to discover lncRNAs that are commonly altered across cancer types, which we termed ‘onco-lncRNAs’. During our analysis, we discovered a novel unannotated onco-lncRNA, onco-lncRNA-230, that was significantly up regulated in head and neck squamous cell carcinoma (HNSC), lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC) tumors relative to matched adjacent normal tissues, when available. We chose to focus on onco-lncRNA-230 as it displayed more than seven fold increase in LUAD and more than thirty seven fold change in LUSC tumors relative to adjacent normal. First, we validated this finding by quantitative PCR which revealed greater than a two fold enrichment of onco-lncRNA-230 expression in two out of seven LUAD and all six LUSC cells lines compared to a normal lung cell line. Because we observed the greatest increase in expression in HCC95 LUSC cells, we next sought to determine if modulating the expression of onco-lncRNA-230 promotes oncogenic phenotypes. Silencing of onco-lncRNA-230 in HCC95 cells did not change cellular proliferation but significantly increased apoptosis. Furthermore, silencing onco-lncRNA-230 resulted in a decrease in cellular invasion by transwell assay. Taken together, this represents the first study reporting that onco-lncRNA-230 is dysregulated in multiple cancer types, significantly up-regulated in lung cancer patient samples and lung cancer cell lines, and confers oncogenic phenotypes. Moving forward, we intend to explore how onco-lncRNA-230 mechanistically promotes lung cancer with the objective of utilizing onco-lncRNA-230 as a novel cancer diagnostic and therapy.
Citation Format: Cynthia Y. Tang, Jessica M. Silva-Fisher, Ha X. Dang, Nicole M. White, Christopher A. Maher. A novel long noncoding RNA, onco-lncRNA 230, induces apoptosis and invasion in lung squamous cell 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 971.
Abstract 979: Identification of a novel long noncoding RNA within the LCK gene locus that regulates prostate cancer cell growth
Authors: Ta Huy Q. , Jackson Samuel R. , Whitworth Hilary , Bhadel Shriti , Gioeli Daniel 
Published: July 2016

Abstract
Prostate cancer remains the second most common type of cancer and frequent cause of cancer-related mortality in American men. Even though many patients with metastatic prostate cancer will initially respond to androgen deprivation therapy, virtually all patients will relapse and develop lethal castration-resistant prostate cancer. Long noncoding RNAs (lncRNAs) are emerging as critical regulatory elements of many cellular biological processes, and there is increasing evidence demonstrating that dysregulation of lncRNAs is associated with many human cancers, including cancers of the prostate, breast, and lung. We have discovered in a high-throughput RNAi screen identifying regulators of prostate cancer cell growth that knockdown of lymphocyte-specific protein tyrosine kinase (LCK) significantly decreases growth of prostate cancer cells in the presence and absence of androgen. Surprisingly, immunoprecipitation and western blot analyses show that LCK is not expressed at the protein level in prostate cancer cells. Rapid amplification of cDNA ends (RACE) and sequencing have revealed that a previously unannotated lncRNA lies within exon six and the 3’UTR of the LCK gene. While short hairpin RNAs (shRNAs) targeting the carboxy-terminus of the LCK gene decreases cell growth, expression of shRNAs specific for the amino-terminus has no effect on growth. Furthermore, only quantitative polymerase chain reaction (qPCR) primers directed toward the 3’ section of the LCK gene yield detectable levels of transcript. These data provide further validation for the existence of a lncRNA within the LCK gene locus. Remarkably, the lncRNA situated within the LCK gene is dramatically upregulated in response to androgen. Therefore, we have labeled this lncRNA “HULLK” for Hormone-upregulated lncRNA within LCK. Cellular fractionation and qPCR show that HULLK predominantly localizes to the cytoplasm. In addition to the effects on prostate cancer cell growth, we have data that alludes to the increase in transcript levels of several Src family members following depletion of HULLK. Thus, these studies indicate that the LCK gene contains a lncRNA involved in the regulation of prostate cancer cell growth and perhaps transcription. While additional analyses will be required to fully characterize HULLK, our data suggest that it may serve as a novel regulator of prostate cancer proliferation.
Citation Format: Huy Q. Ta, Samuel R. Jackson, Hilary Whitworth, Shriti Bhadel, Daniel Gioeli. Identification of a novel long noncoding RNA within the LCK gene locus that regulates prostate cancer cell growth. [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 979.
Abstract 991: Long non-coding RNA LINC01133 inhibits epithelial-mesenchymal transition and metastasis in colorectal cancer by interacting with SRSF6
Authors: Kong Jianlu , Zhang Honghe , Xu Enping , Huang Qiong , Chen Jian , Lai Maode 
Published: July 2016

Abstract
Objective Long non-coding RNAs (lncRNAs) play crucial roles in many biological and pathological processes, including tumor metastasis. The aim of this study was to investigate the expression and molecular function of LINC01133 in colorectal cancer (CRC).
Design LINC01133 expression was assessed in CRC cell lines and 219 clinical tissue samples by quantitative RT-PCR. Small interfering RNA-mediated knockdown was used to probe the biological functions of LINC01133, and its binding protein was isolated and identified using ChIRP-MS combined with western blot, and further validated by RNA immunoprecipitation assays.
Results We found that LINC01133 inhibited CRC cell migration and invasion by regulating the epithelial-mesenchymal transition (EMT), and was downregulated by TGF-β. We then showed that SRSF6 directly bound to LINC01133. Furthermore, we confirmed that that the EMT process regulated by LINC01133 in CRC cells depended on the presence of SRSF6. The expression of LINC01133 was markedly downregulated in CRC tissues relative to their corresponding normal mucosal tissues, and patients with tumors displaying higher LINC01133 expression had a better clinical outcome.
Conclusion These data suggest that LINC01133 inhibits the EMT and metastasis by directly binding to SRSF6 as a target mimic, and may serve as a prognostic biomarker and/or an effective target for anti-metastasis therapies for CRC.
Citation Format: Jianlu Kong, Honghe Zhang, Enping Xu, Qiong Huang, Jian Chen, Maode Lai. Long non-coding RNA LINC01133 inhibits epithelial-mesenchymal transition and metastasis in colorectal cancer by interacting with SRSF6. [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 991.
Abstract 995: The functional involvement of H19, a Long noncoding RNA, in human colorectal cancer
Authors: LING HUI , Ohtsuka Masahisa , Pichler Martin , Ivan Cristina , Matsushita Daisuke , Calin George 
Published: July 2016

Abstract
The clinical significance of long noncoding RNAs (lncRNAs), defined as transcripts longer than 200 bp that do not code for proteins, in colorectal cancer (CRC) remains largely uncharacterized. We selected 10 lncRNAs associated with CRC, analyzed their expression association with patient survival using The Cancer Genome Atlas (TCGA) CRC data, and identified H19 as the one significantly associated with CRC patient survival. Experimental data using CRC cell line models showed that downregulation of H19 significantly reduced cancer cell proliferation, anchorage-independent growth, and cell migration capacity. Flow cytometric analysis suggested a clear G1 arrest of CRC cells following depletion of H19 expression. Our mechanism study suggests that H19 is pivotal in maintaining Wnt signaling and notch signaling. These finding represent a novel mechanism of H19 function in colorectal cancer, and strongly support the translational importance of this lncRNA as cancer marker and therapeutic target.
Citation Format: HUI LING, Masahisa Ohtsuka, Martin Pichler, Cristina Ivan, Daisuke Matsushita, George Calin. The functional involvement of H19, a Long noncoding RNA, in human 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 995.