bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1740: SATB2 localizes to mitotic microtubules and centrosome of cell cycles and regulates G1 phase cell cycle via proteosomal-dependent CDK2 in SKOV-3 ovarian cancer cells.
Authors: Sin Eun Ah , Sohn Eun J. , Jung Ji Hoon , Lee Duckgue , Kim Bonglee , Jung Duck-Beom , Kim Ji-Hyun , Lee Hyo-Jeong , Kim Sung Hoon 
Published: August 2014

Abstract
Though special AT-rich sequence-binding protein 2 (SATB2) is known as a transcriptional regulator of skeletal development and osteogenic differentiation, the underlying role of SATB2 still remains unclear. In the present study, we found that SATB2 localized to the mitotic microtubules, centrosome and midbodies in mitotic cells with α-tubulin. SATB2 knockdown by siRNA transfection reduced the cell viability, and increased the number of ethidium homodimer positive stained cells in SKOV3 ovarian cancer cells. Consistently, cell cycle analysis revealed that SATB2 knockdown accumulated G1 arrest and downregulated the cyclin-dependent kinase 2 (CDK2) expression by western blotting, while immunofluorescence assay revealed that CDK2 and SATB2 were co-localized in SKOV3 cells. Furthermore, proteosomal inhibitor MG132 treatment reversed the downregulation of CDK2 induced by SATB2 knockdown in SKOV3 cells. Overall, our findings suggest that SATB2 regulates the mitosis and G1 phase cell cycle via proteosomal ubiquitination in SKOV3 ovarian cancer cells.
Citation Format: Eun Ah Sin, Eun J. Sohn, Ji Hoon Jung, Duckgue Lee, Bonglee Kim, Duck-Beom Jung, Ji-Hyun Kim, Hyo-Jeong Lee, Sung Hoon Kim. SATB2 localizes to mitotic microtubules and centrosome of cell cycles and regulates G1 phase cell cycle via proteosomal-dependent CDK2 in SKOV-3 ovarian cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1740. doi:10.1158/1538-7445.AM2013-1740
Abstract 1754: Dormant cancer cells are resistant to conventional therapies and induce tumor vessels after chemotherapy.
Authors: Yano Shuya , Mii Sumiyuki , Tome Yasunori , Hiroshima Yukihiko , Uehara Fuminari , Miwa Shinji , Fujiwara Toshiyoshi , Hoffman Robert M. 
Published: August 2014

Abstract
Dormant cancer cells were visualized with a fluorescence ubiquitination cell cycle indicator (FUCCI). FUCCI-expressing xenografts were established from MKN45 gastric cancer cells. Within 7 days after inoculation, FUCCI-expressing nascent tumors contained a mixture of cancer cells in G0/G1 phase and in S/G2/M phases. Nascent tumors treated with cyto-toxic agents showed that cancer cells in G0/G1 phase can survive and become dormant. As tumors grew, the proliferating area was only at the surface and the dormant area predominated. Chemotherapy killed only the minority population of proliferating cancer cells at the surface and had little effect on the majority of dormant cancer cells in the tumor center. Furthermore, we investigated tumor chemoresistance using nestin-driven GFP transgenic mice that have GFP-expressing nascent tumor vessels. Chemotherapy-treated tumors had much more and deeper tumor vessels than control tumors, suggesting that dormant cancer cells may protect themselves by inducing tumor vessels. This report suggests that dormant cancer cells play a large role in drug resistance.
Citation Format: Shuya Yano, Sumiyuki Mii, Yasunori Tome, Yukihiko Hiroshima, Fuminari Uehara, Shinji Miwa, Toshiyoshi Fujiwara, Robert M. Hoffman. Dormant cancer cells are resistant to conventional therapies and induce tumor vessels after chemotherapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1754. doi:10.1158/1538-7445.AM2013-1754
Abstract 1757: Gelfoam® histoculture enables cancer cells to mimic in vivo cell cycle behavior.
Authors: Yano Shuya , Mii Sumiyuki , Tome Yasunori , Hiroshima Yukihiko , Uehara Fuminari , Miwa Shinji , Hoffman Robert M. 
Published: August 2014

Abstract
Tumors in vivo are well known to behave quite differently from cancer cells cultured on plastic or glass plates (monolayer culture). Therefore, cancer cell-cycle kinetics were visualized in Gelfoam® 3D-histoculture using HeLa cells and MKN45 cells expressing fluorescence ubiquitination cell cycle indicator (FUCCI), whereby quiescent cancer cells express mKusabira-Orange fluorescent protein (red) and proliferating cells express mAzami-Green fluorescent protein (green). Gelfoam® histoculture of FUCCI-expressing cancer cells results in tumor-like structures with quiescent cancer cells in the center and proliferating cells at the surface, similar to what occurs in vivo as visualized by FUCCI confocal microscopy. These results have profound implications for cell cycle studies, since most cellular and molecular studies of the cancer cell cycle are performed on plastic monolayer culture where characteristics of the cells may be quite different from the tumor in vivo.
Citation Format: Shuya Yano, Sumiyuki Mii, Yasunori Tome, Yukihiko Hiroshima, Fuminari Uehara, Shinji Miwa, Robert M. Hoffman. Gelfoam® histoculture enables cancer cells to mimic in vivo cell cycle behavior. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1757. doi:10.1158/1538-7445.AM2013-1757
Abstract 1764: Overexpression of the DNA repair regulator PARI in pancreatic cancers promotes genomic instability and tumorigenesis.
Authors: O'Connor Kevin , Dejsuphong Donniphat , D'Andrea Alan , Moldovan George-Lucian 
Published: August 2014

Abstract
Inappropriate homologous recombination (HR) causes genomic instability and cancer. We recently showed that the protein PARI, containing a UvrD-like helicase domain, is a novel PCNA interacting partner, required for preservation of genome stability in human and DT40 chicken cells (Moldovan et al, Molecular Cell 2012). Using cell-based and biochemical assays, we showed that PARI restricts unscheduled recombination by interfering with the formation of RAD51-DNA HR structures. Thus, we proposed that PARI is a long sought-after factor that suppresses inappropriate recombination events at mammalian replication forks.
We recently found that PARI is specifically overexpressed in pancreatic cancer cells (O'Connor et al, Cancer Research, in revision). PARI up-regulation results in DNA repair deficiency and genomic instability. Importantly, PARI knockdown compromises the proliferation of pancreatic cancer cells in vitro. PARI depletion results in an altered cell cycle, defined by S-phase accumulation, perturbed DNA replication, and activation of the DNA damage response pathway in the absence of exogenous DNA damage. Moreover, we found that in pancreatic cancer cells, PARI overexpression results in DNA damage tolerance by promoting replication of damaged DNA. Finally, using a xenograft tumor model in nude mice we show that PARI knockdown reduces pancreatic tumor growth in vivo. Thus, our work suggests that PARI is a potential target for pancreatic ductal adenocarcinoma therapy.
Citation Format: Kevin O'Connor, Donniphat Dejsuphong, Alan D'Andrea, George-Lucian Moldovan. Overexpression of the DNA repair regulator PARI in pancreatic cancers promotes genomic instability and tumorigenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1764. doi:10.1158/1538-7445.AM2013-1764
Abstract 1785: Ubiquitin specific protease 3 is a regulator of histone ubiquitination required for maintenance of genomic stability.
Authors: Sharma Nidhi , Zhu Qianzheng , Wang Qi-En , Wani Altaf A. 
Published: August 2014

Abstract
The ubiquitination of histones is crucial for the maintenance of genomic stability. Little is understood about the deubiquitinating enzymes that catalyze the removal of ubiquitin from histones in response to UV damage. In this study, we identify the ubiquitin-specific protease 3 (USP3) as a deubiquitinating enzyme which catalyzes the cleavage of ubiquitin from γH2AX and uH2A in response to UV damage. Using GFP-tagged USP3 we demonstrate that USP3 is a nuclear protein. To determine the function of USP3 in chromatin regulation we ectopically expressed USP3 in Hela cells and analyzed the ubiquitination status of histones. Our analysis demonstrated that the overexpression of the wild type USP3 (USP3wt), but not the catalytically inactive mutant (USP3C1685) resulted in a decrease in the ubiquitination of γH2AX and uH2A. This result was further supported by the functional ablation of USP3 by RNAi. The efficient reduction of the USP3 protein was accompanied by a significant increase in the levels of uH2A and the ubiquitination of γH2AX. In addition, we were also able to demonstrate that the depletion of USP3 increases the persistence of uH2A and Fk2 foci formation in response to UV damage. Together, our results implicate that USP3 is involved in the removal of ubiquitin marks from chromatin-bound proteins as a means to attenuate the damage signal. Thus, in the presence of UV damage, the functional ablation of USP3 may lead to a delay in cell cycle progression and the activation of checkpoint signals, which in turn could induce genotoxic stress. This work was supported by the PHS grant ES2388, ES12991 and CA93413.
Citation Format: Nidhi Sharma, Qianzheng Zhu, Qi-En Wang, Altaf A. Wani. Ubiquitin specific protease 3 is a regulator of histone ubiquitination required for maintenance of genomic stability. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1785. doi:10.1158/1538-7445.AM2013-1785
Abstract 1786: UV damage-induced histone H3 lysine 56 deacetylation regulates nucleotide excision repair and checkpoint signaling.
Authors: Battu Aruna , Wani Altaf Ahmad 
Published: August 2014

Abstract
Nucleotide excision repair (NER) is the major pathway in cells for the removal of bulky photoproducts and ensuring integrity of the genome. NER constitutes lesion recognition, excision of damaged DNA, synthesis of a DNA fragment, and ligation of the repair patch. Nonetheless, DNA within the cells is compacted into chromatin and lesion recognition requires chromatin to be remodeled to permit access of repair and checkpoint machinery to the damage site. Consequent to repair of the lesions, chromatin structure is restored to its original state so that cells resume cell cycle progression. Although several reports have demonstrated the role of chromatin remodelers, histone modifications and histone chaperones in DNA damage response (DDR), knowledge of how these epigenetic mechanisms control the DDR is largely in its infancy. We and others have recently observed that histone H3 is deacetylated on lysine 56 immediately in response to UV-induced DNA damage. Acetylation is promptly restored upon completion of repair and is necessary for recovery from DNA damage induced cell cycle arrest. However, the function of H3K56 deacetylation in the DDR remains to be determined. We found that UV-induced deacetylation of H3K56 is abrogated in the presence of TSA and sodium butyrate, both of which inhibit class I histone deacetylases (HDACs). Knockdown of either HDAC1 or HDAC2 alone did not affect UV-induced deacetylation of H3K56. However, simultaneous knockdown of both HDAC1 and 2 resulted in retention of H3K56 acetylation after UV irradiation. Consistently, both HDAC1 and HDAC2 localized to sites of UV damage. These observations are consistent with that reported by Miller et. al., indicating that HDAC1 and HDAC2 are responsible for the deacetylation of H3K56 in response to DNA damage. Since the deacetylation of H3K56 is one of the most immediate responses to UV-irradiation, we assumed it to play a crucial role in NER. Accordingly, we observed that CPD removal was affected in H1299 cells with histone H3K56Q mutation that mimics constitutive acetylation. Furthermore, we found that localization of the checkpoint kinase ATM to UV damage sites was affected in these cells. Consequently, ATM-mediated H2AX phosphorylation was also found to be defective in the mutant cells. Based on our observations, we speculate that HDAC1 and 2 mediated H3K56 deacetylation regulates NER and checkpoint signaling cascade in response to UV damage.
This work was supported by PHS grants ES2388, ES12991 and CA93413 and Pelotonia postdoctoral fellowship to AB.
Citation Format: Aruna Battu, Altaf Ahmad Wani. UV damage-induced histone H3 lysine 56 deacetylation regulates nucleotide excision repair and checkpoint signaling. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1786. doi:10.1158/1538-7445.AM2013-1786
Abstract 1797: Differential gene expression profiles of FFPE samples with SensationPlus™ and GeneChip™ arrays.
Authors: Chamnongpol Sangpen , Ujvari Andrea , Kourennaia Olga , Myers Kim , Bowers Lisa , Fisher Jesse , Post Marc , Kubu Chris 
Published: August 2014

Abstract
Formalin-fixed and paraffin-embedded (FFPE) tissue samples represent a largely untapped wealth of information on the transcriptional states of clinically archived materials for retrospective studies. Although the RNA is degraded during fixation and storage and has been considered unusable, Affymetrix has developed SensationPlus™, a target-preparation method that allows transcriptional profiling from 20 ng of FFPE total RNA using GeneChip™ arrays. We will demonstrate that SensationPlus™ expression profiles from decade old FFPE materials are extremely similar to data from their matched fresh frozen (FF) RNA counterparts.
Citation Format: Sangpen Chamnongpol, Andrea Ujvari, Olga Kourennaia, Kim Myers, Lisa Bowers, Jesse Fisher, Marc Post, Chris Kubu. Differential gene expression profiles of FFPE samples with SensationPlus™ and GeneChip™ arrays. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1797. doi:10.1158/1538-7445.AM2013-1797
Abstract 1805: LSD1 regulation of SKP2 expression in prostate cancer.
Authors: Ding Liya , Huang Haojie 
Published: August 2014

Abstract
Prostate carcinogenesis is a complicated process involving both genetic and epigenetic changes. Aberrant expression of LSD1 (Lysine-specific demethylase 1) has been reported in human prostate cancers. Although high expression of LSD1 is implicated in prostate tumorigenesis, the underlying molecular mechanisms are not fully understood. Here we reported that LSD1 promotes proliferation and migration of prostate cancer cells via up-regulation of SKP2 expression. Knockdown of LSD1 using small interfering RNA (siRNA) decreases SKP2 expression and inhibits prostate cancer cell proliferation and migration. Promoter luciferase reporter and chromatin immunoprecipitation (ChIP) experiments show that LSD1 regulates SKP2 expression by controlling the levels of H3K4 methylation in SKP2 promoter and this function of LSD1 is mediated through its demethylase activity. As demonstrated by immunohistochemistry, LSD1 and SKP2 proteins positively correlate with each other and their expression is associated with cell proliferation in human prostate cancer tissues. Our data not only identify SKP2 as a direct regulated target gene of LSD1 but also reveal that SKP2 plays an important role in contributing LSD1 mediated prostate cancer cell proliferation and migration, suggesting that the LSD1-SKP2 axis can serve as therapeutic targets for treatment of prostate cancers.
Citation Format: Liya Ding, Haojie Huang. LSD1 regulation of SKP2 expression in prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1805. doi:10.1158/1538-7445.AM2013-1805
Abstract 1806: AP-1 transcriptionally regulates expression of miR-155 in colon cancer cells.
Authors: Onyeagucha Benjamin C. , Mercado-Pimentel Melania , Flemington Erik , Nelson Mark A. 
Published: August 2014

Abstract
Accumulating evidence indicates elevated S100P promotes the pathogenesis of cancers, including colon cancer. S100P exerts its effects by binding to and activating the Receptor for Advance Glycation End-products (RAGE). The effects of up-regulated S100P/RAGE signaling on cell functions are well documented. Despite these overwhelming evidences, little is known about the downstream targets of S100P/RAGE signaling. In the present study, we demonstrated for the first time that activation of RAGE by S100P regulates oncogenic microRNA-155 (miR-155) expression through Activator Protein-1 (AP-1) stimulation in colon cancer cells. Both S100P and miR-155 expressions are up-regulated in colon tumor specimens. Ectopic S100P expression leads to elevation of miR-155 level. Conversely, knockdown of S100P results in a decrease in miR-155 levels. Exogenous S100P induces miR-155 expression, but blockage of the RAGE receptor with anti-RAGE antibody suppresses the induction of miR-155 by exogenous S100P. Attenuation Blockage of AP-1 activation by S100P, through pharmacological inhibition of MEK activation or genetic inhibition of c-Jun activation using dominant negative c-Jun (TAM67) suppresses miR-155 induction by exogenous S100P. Exogenous S100P treatment stimulates the enrichment of c-Fos, an AP-1 family member at the miR-155 promoter site. Finally, functional study shows that miR-155 knockdown decreases colon cancer cell cell cell growtholon formation and motilityotility in S100P stably transfected cells and parental cells. Taken together, these data demonstrate that the expression of miR-155 is regulated by S100P is dependent on RAGE activation and stimulation of AP-1. Furthermore, the results show that miR-155 is a downstream target of S100P/RAGE signaling and a critical player in S100P functions in colon cancer cells.
Citation Format: Benjamin C. Onyeagucha, Melania Mercado-Pimentel, Erik Flemington, Mark A. Nelson. AP-1 transcriptionally regulates expression of miR-155 in colon cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1806. doi:10.1158/1538-7445.AM2013-1806
Abstract 1830: Cancer-associated variants at 8q24 are correlated with expression of adjacent long non-coding RNAs involved in cell cycle regulation.
Authors: Kim Taewan , Croce Carlo M. 
Published: August 2014

Abstract
The mechanism by which cancer risk variants at 8q24.21 increase cancer risk is unclear for lack of protein-coding genes in the region, although such variants have been strongly associated with cancer development. By sequencing three colorectal cancer-associated variants and examining the expression levels of the lncRNAs at 8q24.21, we show that expression of long non-coding RNAs (lncRNAs) in the region is correlated with risk alleles of the cancer-associated variants. We further report that the lncRNAs regulate cell cycle by modulating expression of cell cycle-related genes such as CDKN1A and GADD45, suggesting the potential oncogenic functions of the lncRNAs. Our data provide new insight of disease-related variants in a gene desert.
Citation Format: Taewan Kim, Carlo M. Croce. Cancer-associated variants at 8q24 are correlated with expression of adjacent long non-coding RNAs involved in cell cycle regulation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1830. doi:10.1158/1538-7445.AM2013-1830
Abstract 1832: Integrated analysis of clinical ChIPSeq data and public databases identified candidate long non-coding RNAs critically involved in gastrointestinal cancer.
Authors: Maruyama Reo , Yamamoto Eiichiro , Kumegawa Kohei , Tsuyada Akihiro , Ashida Masami , Suzuki Ryo , Tokino Takashi , Shinomura Yasuhisa , Suzuki Hiromu 
Published: August 2014

Abstract
Recent work has suggested various important functions and molecular mechanisms for long non-coding RNAs (lncRNAs) and they are also thought to play critical roles in cancer. However the importance of lncRNAs in cancer biology is still unclear. In this study, we sought to comprehensively identify novel lncRNAs that are critically involved in tumorigenesis and progression in gastrointestinal cancer. To identify candidate lncRNAs, we have applied the ChIP-Seq technology to clinical endoscopic biopsy specimens and characterized global histone modification patterns in more than 30 normal tissues and cancers. We developed an original lncRNA database based on several public databases. We then examined histone methylation status around putative lncRNAs and generated a list of candidate lncRNAs that may be important for cancer. In order to narrow the list down, we also utilized publicly available ChIPSeq data as well as bisulfite sequencing and RNASeq data to perform integrated analysis. Finally we identified ∼10 lncRNAs that are abnormally silenced by DNA methylation in gastrointestinal cancer and also identified other ∼10 lncRNAs that are abnormally overexpressed and potentially acting as oncogenic genes in cancer. We are examining gene expression level and epigenetic status of these lncRNAs in cancer cell lines and specimens by qRT-PCR, MSP, bisulfite pyro-sequencing and ChIP assay. Here we would like to show the advantage of making the best use of publicly available multi-omics data to promote long non-coding RNA research.
Citation Format: Reo Maruyama, Eiichiro Yamamoto, Kohei Kumegawa, Akihiro Tsuyada, Masami Ashida, Ryo Suzuki, Takashi Tokino, Yasuhisa Shinomura, Hiromu Suzuki. Integrated analysis of clinical ChIPSeq data and public databases identified candidate long non-coding RNAs critically involved in gastrointestinal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1832. doi:10.1158/1538-7445.AM2013-1832