bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2476: Discovery of an androgen-responsive long noncoding RNA that associates with progression of ERG-overexpressing prostate cancers
Authors: Kohvakka Annika , Shcherban Anastasia , Kivinummi Kati K. , Annala Matti , Urbanucci Alfonso , Nykter Matti , Visakorpi Tapio 
Published: August 2018

Abstract
Androgen receptor (AR) signaling pathway has an important role in the growth and development of normal prostate, but also in tumorigenesis and progression of prostate cancer (PC). Although the mechanisms of AR signaling have been widely studied and utilized for treatment in advanced PC, the exact role of AR in development of primary PC is unclear. Former studies have found that AR cistrome is reprogrammed during tumorigenesis to bind novel genomic loci by master regulators, including the ETS family transcription factor ERG. While many AR-induced target genes are known, the effect of AR signaling on regulation of long noncoding RNAs (lncRNAs) is poorly understood, especially in the context of PC progression. Previously, we discovered multiple novel PC-associated transcripts (PCATs) to be aberrantly expressed in PC. Here, we evaluated the expression of 39 Tampere PCATs (TPCATs) in 87 radical prostatectomy specimens using high-throughput real-time PCR, and studied their association with time to PSA progression after prostatectomy. Six TPCATs were significantly associated with time to PSA progression, and four of them also associated with extracapsular extension. In addition, we assessed the expression of TPCATs in the TCGA prostate adenocarcinoma cohort, and found many to be correlated with ERG expression. Moreover, publicly available AR ChIP-seq data from PC tumors indicated that several ERG-associated TPCATs had AR-binding sites on their promoters, some of which overlapped with ERG binding sites. Most notably, we found one progression-associated TPCAT that was regulated by AR in an androgen-sensitive manner according to AR siRNA knockdown and DHT stimulation experiments in vitro. The same TPCAT was also highly associated with overexpression of ERG, and further validated to be a highly PC-specific lncRNA that was abundantly expressed in primary PCs. Taken together, these findings give more insight into the role of AR cistrome in the regulation of lncRNAs in primary PC, and introduce a potential novel prognostic marker to be used in early detection of aggressive PC.
Citation Format: Annika Kohvakka, Anastasia Shcherban, Kati K. Kivinummi, Matti Annala, Alfonso Urbanucci, Matti Nykter, Tapio Visakorpi. Discovery of an androgen-responsive long noncoding RNA that associates with progression of ERG-overexpressing prostate cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2476.
Abstract 2479: LncRNA GAS8-AS1 directs epigenetic modulation of the tumor suppressor GAS8 via MLL1/WDR5 to suppress hepatocarcinogenesis
Authors: Yang Ming 
Published: August 2018

Abstract
Long noncoding RNAs (lncRNAs) are vital players in hepatocellular carcinoma (HCC). We previously identified a significantly mutated lncRNA GAS8-AS1 locating in intron 2 of GAS8. However, its involvement in HCC is still largely unknown. In this study, we thoroughly functional evaluated its critical role in regulating chromatin dynamics, gene expression, cancer development and sorafenib multi-kinase target therapy in HCC. We for the first time declare that GAS8-AS1 and its host gene GAS8 act as novel HCC tumor suppressors employing a series of in vitro and in vivo assays. Consistent with this notion, a significantly decreased GAS8-AS1 or GAS8 expression exists in HCC tissues and is associated with poor prognosis of HCC patients. Interestingly, lncRNA GAS8-AS1 could evidently promote GAS8 transcription. Although GAS8-AS1 does not impact promoter DNA methylation of GAS8, we successfully annotated two lncRNA interacting proteins, Mixed Lineage Leukemia 1 (MLL1), a histone 3 Lys4 (H3K4) methyltransferase, and its partner WD-40 Repeat Protein 5 (WDR5) based on bioinformatics methodology. Chromatin immunoprecipitation and RNA immunoprecipitation assays elucidate that lncRNA GAS8-AS1 is required to maintain the GAS8 promoter in an open chromatin state. In accord with this, knockdown of GAS8-AS1 results in reduced MLL1/WDR5 binding, decreased H3K4me3 levels, diminished RNA Pol II functions and gene silencing of GAS8. GAS8-AS1 may function as part of a surveillance mechanism that keep activation of GAS8 promoter and transcription, which thus prevents hepatocarcinogenesis. Our results highlight the prevalent involvement of regulatory lncRNAs in cancers and provide pathogenic insights into HCC development and treatment.
Citation Format: Ming Yang. LncRNA GAS8-AS1 directs epigenetic modulation of the tumor suppressor GAS8 via MLL1/WDR5 to suppress hepatocarcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2479.
Abstract 2486: PTEN fusion gene promotes growth in cancer
Authors: Yu Yanping , Chang Silvia , Ren Baoguo , Michalopoulos George , Tseng George , Luo Jianhua 
Published: August 2018

Abstract
Deletion or mutation of PTEN is frequent in a variety of human cancers and is an underlying mechanism for cancer development. Here, we report a PTEN-involved fusion gene and the corresponding genome breakpoint in human cancers. Pten fusion is highly recurrent in cancers and their matched lymph nodes and is located nucleoli. Targeted knockout of this fusion gene in Du145 and MCF7 cells impeded tumor cell growths, retarded S phase entry, and reduced invasiveness, and was prone to the UV- induced apoptosis. Knockout of PTEN-fusion blocked xenografted-tumor growth in mice, while forced-expression of PTEN -fusion through hydrodynamic injection into mice led to hepatocellular carcinoma. These findings indicate that the genome rearrangement of PTEN-fusion results in an oncogenic fusion protein in addition to the loss of Pten as an underlying mechanism in driving cancer development.
Citation Format: Yanping Yu, Silvia Chang, Baoguo Ren, George Michalopoulos, George Tseng, Jianhua Luo. PTEN fusion gene promotes growth in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2486.
Abstract 249: Genome-scale analysis of aberrant DNA methylation for emerging, high incidence of colorectal cancer in Taiwan
Authors: Chen KuoHsing , Lai Liang-Chuan , Chang Hsien-Fang , Chao Yu-Liang , Lin Been-Ren , Liang Jin-Tung , Cheng Ann-Lii , Chuang Eric Y. , Yeh Kun-Huei 
Published: August 2018

Abstract
Background:
The incidence of colorectal cancer (CRC) in Taiwan is increasing in decades, and the definite etiology remains elusive. This study aimed to explore the association of aberrant DNA methylations and the development of colorectal cancer in Taiwan.
Materials and methods: We prospectively collected 27 CRC patients' tumors, the adjacent normal colons (frozen specimens), and clinical characteristics, including age, sex, body mass index (BMI), stage at diagnosis and medical history of diabetes mellitus and hyperlipidemia. We conducted a genome-scale analysis of DNA methylation in these 27 CRC and 5 adjacent normal colon samples by using Illumina Methylation EPIC Beadchips. We used Wilcoxon rank-sum test (p &lt; 0.05) and β value difference (≧ 0.25 or ≦ -0.25) to evaluate the methylation differences between CRC and adjacent normal colon samples.
Results: Overall, 7,672 differentially methylated genes (DMGs) were found between 27 CRCs and 5 adjacent normal colons. Principle component analysis demonstrated that a distinct cluster of adjacent normal colon and CRC tissue samples. Pathway analysis (β value difference ≧ 0.4 or ≦ -0.4) showed that ERK/MAPK signaling, GP6 signaling, CREB signaling in neurons, CDK5 and IGF-1 pathways were the top 5 pathways that were involved by DMGs. Subgroup analysis revealed most DMGs (N = 5,228) are shared by all 3 subgroups, however, patients who had metabolic syndrome had fewest subgroup-specific DMGs between tumors and adjacent normal colons, compared to patients who had no metabolic syndrome with normal weight or overweight (BMI &lt; 25 or ≧ 25).
Conclusion: We demonstrated a genome-scale difference of aberrant DNA methylation in colorectal cancer in an East Asian population. These data will be validated further in a larger cohort.
Citation Format: KuoHsing Chen, Liang-Chuan Lai, Hsien-Fang Chang, Yu-Liang Chao, Been-Ren Lin, Jin-Tung Liang, Ann-Lii Cheng, Eric Y. Chuang, Kun-Huei Yeh. Genome-scale analysis of aberrant DNA methylation for emerging, high incidence of colorectal cancer in Taiwan [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 249.
Abstract 2490: Characterization of the role of DPPA3 in stemness regulation in hepatocellular carcinoma by DNA methylation
Authors: Yan Qian , Zhang Yu , Yu Dandan , Kam Ngar Woon , Guan Xin-Yuan 
Published: August 2018

Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers in the world with a very poor prognosis, which is closely associated with cancer stem cell (CSC). Global RNA-sequencing was used in different developmental stages of hepatocytes, including embryonic stem cell, endoderm, liver progenitor, and premature hepatocyte, as well as two pairs of nontumor and tumor tissues from HCC patients. We found that Developmental Pluripotency Associated 3 (DPPA3) was highest expressed in the stage of liver progenitor cells, and was down-regulated along with development. In HCC patients, DPPA3 was expressed in less than 1% tumor cells, while no staining was detected in normal counterparts. Functional assays revealed that DPPA3 overexpression increased HCC cells proliferation rate, the ability of foci formation and colony formation in soft agar, as well as migration and invasion. Furthermore, DPPA3 significantly increased HCC cells sphere formation frequency and sensitivity to chemotherapeutic agent including cisplatin, 5-Fu, and Sorafenib. In order to investigate the role of DPPA3 in CSC maintenance and stemness regulation in HCC, whole genome methylation sequencing was applied to compare methylation status between DPPA3- and empty vector-transfected cells. Results showed that DPPA3 reduced CG methylation level within functional regions in the genome. Of the 541 differentially methylated regions, the majority of them were involved in developmental process and cell differentiation. Overall, our findings give a novel insight into how methylation regulation controls the fate of cancer stem cells.
Citation Format: Qian Yan, Yu Zhang, Dandan Yu, Ngar Woon Kam, Xin-Yuan Guan. Characterization of the role of DPPA3 in stemness regulation in hepatocellular carcinoma by DNA methylation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2490.
Abstract 2491: Nuclear exporter protein XPO1 a novel prognostic and therapeutic target in gastric cancer
Authors: Muqbil Irfana , Mahdi Zaid , Choudhary Rahman , Baloglu Erkan , Senapedis William , Landesman Yosef , Shacham Sharon , Kauffman Michael , Kim Steve , Beydoun Rafic , Berri Richard N. , Shields Anthony , Mohammad Ramzi M. , Azmi Asfar S. 
Published: August 2018

Abstract
The high mortality rate associated with Gastric Cancer (GC) indicates the urgent need for actionable therapeutic targets. The nuclear exporter protein exportin 1 (XPO1/CRM1) is the exclusive exporter of many tumor suppressor proteins (TPSs) and growth regulators. XPO1 is often over-expressed in different malignancies leading to aberrant cytoplasmic localization of TSPs and subsequent inactivation. A detailed analysis on the correlation of XPO1 with inflammation-metaplasia-dysplasia-carcinoma sequence progression was performed using immunohistochemistry in 70 GC cases: (a) 10 cases from normal gastric mucosa, (b) 10 cases of stomach with intestinal metaplasia with and without inflammation, (c) 10 cases of mucosa with low-grade dysplasia (d) 10 cases of mucosa with high-grade dysplasia, (e) 10 cases of gastric adenocarcinoma and (f) 20 cases of metastatic gastric carcinoma. A correlation between XPO1 expression, the pathological and clinical features of the disease as well as survival were analyzed. Gastric cancer cell lines were exposed to the Selective Inhibitors of Nuclear Export (SINE) compounds (selinexor, KPT-8602, KPT-185, or the natural agent, leptomycin B (LMB), then analyzed using cytotoxicity and molecular assays. In addition, the activity of selinexor was evaluated in a sub-cutaneous xenograft of gastric cancer cell line NCI-N87. XPO1 served as a prognostic marker for poor outcome as positive staining of XPO1 in GC correlated with aggressive behavior of the disease. Targeting XPO1 using SINE compounds or LMB resulted in inhibition of GC cellular growth (IC50&lt;200 nM), induction of apoptosis and suppression of colony formation (p&lt;0.01). Molecular analysis revealed nuclear retention of several important TSPs, induction of pro-apoptotic proteins and suppression of pro-survival factor Bcl-2. Selinexor given orally at doses of 15 mg/kg twice a week for three weeks caused statistically significant reduction of NCI-N87 tumors in mice (p&lt;0.05). Efficacy studies of SINE compounds in patient derived models of GC are ongoing. Our findings strongly demonstrate the potential of XPO1 to serve not only as a prognostic marker but also as a therapeutic marker in GC that warrants further clinical investigations.
Citation Format: Irfana Muqbil, Zaid Mahdi, Rahman Choudhary, Erkan Baloglu, William Senapedis, Yosef Landesman, Sharon Shacham, Michael Kauffman, Steve Kim, Rafic Beydoun, Richard N. Berri, Anthony Shields, Ramzi M. Mohammad, Asfar S. Azmi. Nuclear exporter protein XPO1 a novel prognostic and therapeutic target in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2491.
Abstract 2496: YY1 regulates the germinal center reaction by inhibiting apoptosis
Authors: Trabucco Sally E. , Zhang Hong 
Published: August 2018

Abstract
The germinal center (GC) reaction produces high-affinity antibodies for a robust adaptive immune response. If dysregulated, the same processes cause GC B cells to become susceptible to lymphomagenesis. It is important to understand how the GC reaction is regulated. In this study, we show that transcription factor YY1 is required to maintain a robust GC reaction in mice. Selective ablation of YY1 significantly decreased in the frequency and number of GC B cells during the GC reaction. This decrease of GC B cells was accompanied by increased apoptosis in these cells. Further, we found that loss of YY1 disrupted the balance between dark zones and light zones, leading to a preferential decrease in dark zone cells. Collectively, these results indicate that YY1 plays an important role in regulating the balance between dark zone and light zone cells in GCs and between survival and death of GC B cells.
Citation Format: Sally E. Trabucco, Hong Zhang. YY1 regulates the germinal center reaction by inhibiting apoptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2496.
Abstract 250: Multiple lines of evidence make ZDHHC3 a possible marker for breast cancer in African American women
Authors: Kinney Nicholas A. , Varghese Robin T. , Anandakrishnan Ramu , Garner Harold R. 
Published: August 2018

Abstract
Rates of breast cancer mortality continue to be divided among race and ethnicity without a definitive explanation. Between the years 2005-2009 the racial disparity in breast cancer mortality caused about 9 extra death per 100 breast cancer cases in African American women compared to Caucasian women. In addition, young African Americans tend to have more aggressive forms of breast cancer. The source of this health disparity likely stems from a complex combination of mammography rate and frequency; segregation; socioeconomic status; and genetics. We contribute to what is known about genetics by investigating microsatellites - a type of repetitive DNA - and possible links to the breast cancer mortality gap. Microsatellites are understudied compared to single nucleotide polymorphisms and have the capacity to affect gene expression. We screen 33,854 microsatellites in germline DNA of African American women with and without breast cancer: four are statistically significant. We preform further analysis of genes harboring these microsatellites; the results reveal that ZDHHC3 is particularly interesting. Its location (3p21) is already linked to early invasive breast cancer. Kaplan-Meier analysis shows that ZDHHC3 alterations may be associated with poor breast cancer survival. Data from cBioPortal suggests that ZDHHC3 mRNA expression is lower in African Americans compared to Caucasians. These independent lines of evidence make ZDHHC3 a candidate for further investigation.
Citation Format: Nicholas A. Kinney, Robin T. Varghese, Ramu Anandakrishnan, Harold R. Garner. Multiple lines of evidence make ZDHHC3 a possible marker for breast cancer in African American women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 250.
Abstract 2502: Role of TMEM97/σ2 receptor in breast cancer cell proliferation and responses to chemotherapy
Authors: Zhang Yuanqin , Wang Jiuhui , Nie Daotai 
Published: August 2018

Abstract
Introduction:
Breast cancer is the most prevalent cancer for women both in the developed and the developing countries. In 2017, about 40,610 women are expected to die from breast cancer in the U.S. The sigma receptors (σRs) are transmembrane receptors with two subtypes, termed sigma-1 receptor and sigma-2 receptor. Sigma-2 receptor has been found overexpressed in numerous human cancer tissues, and compound targeting it are now in clinical trials for breast cancer diagnosis. But it's biological role in breast cancer is unknown because the encoded gene has not been clearly identified. Recently, it has been demonstrated that TMEM97, not progesterone Receptor Membrane Component 1 (PGRMC1), is a bona fide sigma-2 receptor. The identification of sigma-2 (σ2) receptor will make it possible to define its biological functions in breast cancer and develop modulator of σ2 receptor as potential cancer therapeutics.
Methods:
The expression of TMEM97/σ2 receptor in multiple cancer cells was evaluated by RT-qPCR. Regulation of P53 on TMEM97/σ2 receptor was determined by Western Blot after 48 hours Doxorubicin treatment of MCF7 cell and HCT116 wild type and P53-/- cells. PB28, an agonist of σ2 receptor and an antagonist of σ1 receptor, was used (0, 1μM, 10μM and 20μM for 4 days) to test its effects on MCF7 cell growth and colony formation. TMEM97/σ2 receptor was cloned and sequenced. We overexpressed TMEM97/σ2 receptor in MCF7 cells to characterize its role in cell proliferation, survival, and colony formation, with or without treatment of its agonist PB28.
Results and conclusion:
TMEM97/σ2 receptor is expressed in various cancer cell lines including lung, breast and prostate cancer, albeit at different levels. TMEM97 expression was reduced in MCF7 cells when p53 expression was stimulated by doxorubicin. PB28 reduced the number of viable cells and also reduced colony formation of MCF7 cells in a dose dependent manner. Meanwhile overexpression of TMEM97/σ2 receptor retarded cell growth in MCF7 cells and sensitized them to PB28 as evidenced by reduced IC50 when compared with control cells. The data suggest that TMEM97/σ2 receptor is expressed in breast cancer cells, with its expression suppressed by p53, and activation of this receptor led to reduced tumor cell proliferation.
Citation Format: Yuanqin Zhang, Jiuhui Wang, Daotai Nie. Role of TMEM97/σ2 receptor in breast cancer cell proliferation and responses to chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2502.
Abstract 2505: Baicalein reverses chronic stress-induced ovarian cancer promotion through GABA receptors
Authors: Li Ke , Kang Yu , Yu Yinhua 
Published: August 2018

Abstract
Studies suggest that chronic stress accelerate the progression of ovarian cancer, and the promotion effects can be abrogated by β-blockers. However, β-blockers should be assessed and tailored to each cancer patient as they will exert toxic effects in overdose. Baicalein, a widely used Chinese herbal medicine, identified as a new type of anticancer drug with an obvious function of anti-anxiety in animal experiments and whose mechanism may be mediated by GABA receptors. The focus of the current study was to determine whether baicalein could block the effects of chronic stress on tumor growth and investigate the underlying mechanism that relates to GABA receptors. Two kinds of ovarian cancer cell lines (OVCAR-8 and CAOV-3) were selected to be investigated in the inhibitory effect of baicalein on cancer cells. Cell CCK-8 assay, wound healing assay, transwell assay and flow cytometry were used for in vitro experiments. Chronic stress was induced by a restrained stress model in nude mice carrying xenografts in the presence and absence of treatment with baicalein. Xenograft sizes and weight were measured after 4 weeks. Norepinephrine was measured by HPLC and GABA was measured by immunoassays in blood and tumor tissues. Expression of GABA receptors in the xenografts was analyzed by real-time quantitative PCR, western blotting and immunohistochemistry (IHC). Our results showed that ovarian cancer cell lines exhibited significant promotion in the presence of NE concentrations of 10Μm and baicalein concentrations of 10μM could reverse its effects by Cell CCK-8 assay and wound healing assay. Daily restraint stress resulted in significantly increased tumor growth in tumor model of ovarian cancer in nude mice. And this increase was completely blocked with daily baicalein treatment. Chronic stress attenuated expression of GABA receptors in vivo and in vitro; conversely, baicalein increased expression of GABA receptors. Overall, our data suggest that baicalein stimulated GABA receptors activation to reduce tumor growth in ovarian cancer. Considering the stimulatory effects of chronic stress on cancer growth, our study implicates baicalein as a potential medicine for blocking the deleterious effects of chronic stress.
Citation Format: Ke Li, Yu Kang, Yinhua Yu. Baicalein reverses chronic stress-induced ovarian cancer promotion through GABA receptors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2505.