bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4419: FOXP3 mediated transcriptional regulation of microRNAs in breast cancer
Authors: Liu Wei , Gao Song , Li Xin , Hu Fengpin , Wang Lizhong 
Published: August 2018

Abstract
MicroRNAs (miRs) have potential as non-invasive biomarkers, but their relevance as biomarkers is limited by inconsistent results, and their regulatory mechanisms remain elusive. In the present study, our results show that the levels of miR-200c and 141 in tumor cells and in circulation differ for mice and for humans between cases with metastatic breast cancer, cases with localized breast cancer, and healthy female controls. The levels of miR-200c and 141 are low in primary tumor cells but are high in the circulation of patients with metastatic breast cancer. Further, we suggest the potential cell origin of circulating miR-200c and 141 and describe their transcriptional regulation in cultured cells and during tumor progression in animal models of spontaneous breast cancer. These results could provide useful insights in early prediction of tumor metastasis and influence treatment strategies for patients at high risk of developing metastatic breast cancer.
Citation Format: Wei Liu, Song Gao, Xin Li, Fengpin Hu, Lizhong Wang. FOXP3 mediated transcriptional regulation of microRNAs in breast 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 4419.
Abstract 4421: A novel long non-coding RNA competes with endogenous RNA and mediates prostate cancer progression
Authors: Shi Xiao-Lei , Xiao Yu-Tian , Liu Fei , Yang Yue , Nian Xin-Wen , Zhu Ya-Sheng , Ren Shancheng , Sun Yinghao 
Published: August 2018

Abstract
Prostate cancer (PCa) remains the leading cancer among men worldwide. There is a critical need for new biomarkers to predict PCa progression and emerging mechanisms of resistance. Long non-coding RNAs(lncRNAs) play pivotal roles in a plethora of cellular processes. Understanding the molecular mechanisms of lncRNAs implicated in the progression of PCa could have an important impact on cancer detection, diagnosis and prognosis.
We previously identified 17 lncRNAs that were found to be differentially expressed in oriental PCa patients. Here, We focused on one uncharacterized lncRNA, which is highly expressed in locally advanced or metastatic PCa, and named it lncAPP. Silencing of lncAPP in PCa inhibitied proliferation and tumour invasion both in vitro and in vivo, resulting in a less aggressive phenotype. In addition, we found that expression of lncAPP in PCa correlated with epithelial-to-mesenchymal-transition(EMT). Using miRDB and Target Scan prediction algorithm, we identified a list of putative lncAPP-binding miRNAs. Specifically, using RNA immunoprecipitation assay and luciferase reporter assay, we demonstrated that lncAPP functions as a molecular sponge for miR218 to facilitate expression of ZEB2 and CDH2.
In conclusion, we discovered a novel lncRNA which is highly expressed in PCa patients of poor prognosis. The expression of lncAPP is associated with tumor progression. We conclude that lncAPP is an intriguing therapeutic target in PCa.
Citation Format: Xiao-Lei Shi, Yu-Tian Xiao, Fei Liu, Yue Yang, Xin-Wen Nian, Ya-Sheng Zhu, Shancheng Ren, Yinghao Sun. A novel long non-coding RNA competes with endogenous RNA and mediates prostate cancer progression [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 4421.
Abstract 4426: Automated miRNA purification from plasma, serum or exosomes
Authors: Mandrekar Michelle , English Jami , Horejsh Douglas , Moreland Chris , Karlen Herly , Urh Marjeta 
Published: August 2018

Abstract
Introduction: MicroRNAs (miRNAs) are endogenous small noncoding RNAs 18-24 nucleotides in size that play important roles involving gene regulation associated with cancer, disease control and gene silencing. Because of the impact on disease progression, miRNA research is rapidly shifting towards biomarker discovery. Many of the commercially available miRNA purification methods involve organic extraction during preprocessing. Here, we describe a novel chemistry that enables RNA purification including smaller RNA such as miRNA. This chemistry offers significant advantages with a simple automated workflow, no organic extraction and minimal preprocessing.
Method: In this study we show successful purification of small RNA, including miRNA, from 100uL to 500uL liquid samples utilizing a novel chemistry on the Maxwell® RSC instrument, which can process between 1 and 16 samples. Proteinase K and Lysis Buffer C are added to the liquid samples and incubated before being transferred to the Maxwell cartridge for miRNA isolation. Sample types tested include plasma, serum and isolated exosomes. The miRNA were evaluated using RT-qPCR including miR-16, miR-21, and let-7a.
Results: The eluates had high levels of small RNA including miRNA at levels comparable to manual competitor methods that require organic extraction. Quantitative PCR showed that the eluates had little or no detectable DNA contamination. Integration of the chemistry onto this automated platform reduced hands-on time while maintaining high quality needed for use in downstream RT-qPCR amplification assays.
Summary: This novel chemistry and method enables purification of small RNA from a range of samples types and volumes. The purified RNA has little or no detectable DNA contamination. Phenol extraction is not required, improving safety and simplifying waste disposal. Also, the automation of this workflow decreases manual hands-on time, saving scientist time and reducing the risk of RNase contamination.
Citation Format: Michelle Mandrekar, Jami English, Douglas Horejsh, Chris Moreland, Herly Karlen, Marjeta Urh. Automated miRNA purification from plasma, serum or exosomes [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 4426.
Abstract 4430: Genistein regulates non-coding RNA HOTAIR and epithelial-to-mesenchyme transition in renal cancer cells
Authors: Sumida Mitsuho I. , Tanaka Yuichiro , Dahiya Rajvir , Yamamura Soichiro 
Published: August 2018

Abstract
Renal cell carcinoma (RCC) is one of the most common malignancies. Despite the development of therapeutic regimens, the prognosis of patients with RCC is poorly understood. Genistein, a naturally occurring isoflavone, has been reported to have anti-cancer effects on a variety of cancer types. While several studies have shown that genistein inhibits kidney cancer progression in various in vitro and in vivo models, the basic molecular mechanisms of genistein action have not been investigated in kidney cancer. In malignancies, long non-coding RNAs (lncRNAs) are differentially expressed in various tissues and have important functions in cell proliferation, motility and apoptosis. HOX transcript antisense RNA (HOTAIR) is a lncRNA localized in the Homeobox C gene cluster on chromosome 12. HOTAIR is necessary to target the polycomb repressive complex 2 (PRC2) in trans to the HOXD locus and can interacts with (PRC2, which enhances H3K27 trimethylation and represses the expression of tumor suppressors. HOTAIR is highly expressed in various cancers and involved in their progression and metastasis. In our study, we investigated the molecular mechanisms of genistein action through a novel pathway that represses HOTAIR. We found that HOTAIR expression is higher in renal cancer cell lines compared to normal controls. Genistein treatment was found to significantly decrease HOTAIR expression in renal carcinoma cell lines (786-O and ACHN cells). Genistein treatment also reduced expression of epithelial-to-mesenchyme transition (EMT)-related proteins, causing reduced cell migration, invasion, and increased apoptosis. We performed RNA immunoprecipitation assays, and found that genistein inhibits HOTAIR binding to PRC2. One of the other EMT markers, a tight junction protein ZO-1, is upregulated by genistein. We further investigated whether genistein represses PRC2 recruitment to the ZO-1 promoter by inhibiting binding of HOTAIR to PRC2. In this study, we revealed detailed mechanism of antitumor action of genistein. These insights indicate that genistein is a potent therapeutic agent not only for renal cancer but also for a broad spectrum of cancers.
Citation Format: Mitsuho I. Sumida, Yuichiro Tanaka, Rajvir Dahiya, Soichiro Yamamura. Genistein regulates non-coding RNA HOTAIR and epithelial-to-mesenchyme transition in renal cancer cells [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 4430.
Abstract 4433: Upregulation of BLU tumor suppressor gene by miR-34a
Authors: Ohno Shinichiro , Sambu Yoshihiro , Oikawa Keiki , Naito Yoshitaka , Harada Yuichirou , Kuroda Masahiko 
Published: August 2018

Abstract
miR-34a is down-regulated in several tumor tissues and well known as strong tumor suppresser miRNA. However, the mechanisms of tumor suppression by miR-34a remain unclear. To elucidate the mechanisms of tumor suppression by miR-34a, we performed microarray analysis of miR-34a transfected cells. Interestingly, we found that the number of up-regulated genes was larger than down-regulated genes by the transfection of miR-34a. The tumor suppresser BLU (ZMYND10) is strongly up-regulated by miR-34a that primarily expressed in the normal lung and down-regulated in non-small cell lung cancer (NSCLC). Therefore, we investigated the possibility that miR-34a inhibits lung cancer development through inducing BLU expression. It was recently reported that miRNA also regulate transcription in the nucleus through binding to the lncRNA from promoter locus. Because, the predicted two binding sites of miR-34a are located in the BLU promoter locus, we searched the lncRNA expressed from the BLU promoter locus. As a result, we identified the lncRNA from the BLU promoter and siRNA against the lncRNA also induced BLU expression. These results suggest that miR-34a induced tumor suppresser BLU through the binding to the promoter-associated lncRNA.
Citation Format: Shinichiro Ohno, Yoshihiro Sambu, Keiki Oikawa, Yoshitaka Naito, Yuichirou Harada, Masahiko Kuroda. Upregulation of BLU tumor suppressor gene by miR-34a [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 4433.
Abstract 4449: Synthetic lethality between CSTF2 and CSTF2T in lung adenocarcinoma and melanoma cell lines
Authors: Popow Johannes , Wieshofer Corinna , Schlattl Andreas , Woehrle Simon , Neumüller Ralph , Petronczki Mark P. , Boettcher Jark , Koegl Manfred , Pearson Mark 
Published: August 2018

Abstract
Genomic instability is a hallmark of cancer and can result in the deletion of genes with no apparent or as yet unknown relevance to tumor survival and proliferation. Although the deletion of such genes may be tolerated due to functional compensation it, however, entails a cancer cell specific vulnerability as the tumor cell relies on the function of compensating redundant genes. Recurrent deletions of cleavage stimulation factor subunit 2 Tau (CSTF2T) have been observed in several tumor samples (TCGA). During meiosis CSTF2, a paralogue of CSTF2T, which resides on the X-chromosome, is transcriptionally silenced and the zygote depends on the activity of CSTF2T. As a result, CSTF2T knockout mice exhibit male sterility which corroborates that CSTF2 and CSTF2T form a functionally redundant pair of genes with an essential function (Dass et al. 2007). With the aim to apply these findings to tumor biology, we therefore tested whether tumor cells with homozygous CSTF2T deletions depend on CSTF2 using CRISPR-based growth competition assays and confirmed this concept in lung adenocarcinoma and melanoma cell line models. Our data establish synthetic lethality between CSTF2 and CSTF2T and suggest inhibition of CSTF2 in CSTF2T deficient tumors as a new therapeutic concept.
Citation Format: Johannes Popow, Corinna Wieshofer, Andreas Schlattl, Simon Woehrle, Ralph Neumüller, Mark P. Petronczki, Jark Boettcher, Manfred Koegl, Mark Pearson. Synthetic lethality between CSTF2 and CSTF2T in lung adenocarcinoma and melanoma cell lines [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 4449.
Abstract 4462: RUNX1 global binding and gene regulation in mammary epithelial cells revealed novel Runx1 mediated cellular activities
Authors: Hong Deli , Fritz Andrew J. , Tye Coralee E. , Page Natalie A. , Boyd Joseph R. , Lian Jane B. , Stein Janet L. , Stein Gary S. 
Published: August 2018

Abstract
The transcription factor RUNX1 is one of the most frequently mutated genes in breast tumors. However, the role of RUNX1 in the mammary gland is understudied. Previously, our group established that RUNX1 has tumor suppressor activities in both normal mammary epithelial and breast cancer cells, including inhibition of epithelial to mesenchymal transition (EMT), migration, and invasion. To better understand the cellular consequences mediated by RUNX1 loss-of-function in mammary epithelial cells, we performed global gene expression profiling (RNA-seq) in Runx1-depleted MCF10A cells. Upon loss of RUNX1, the expression of 1806 genes was significantly altered (with 2-fold change cutoff). Pathway analysis on these differentially expressed genes revealed that RUNX1 is involved in many cellular activities, including lipid metabolism, cell growth and cell cycle control, which were not previously reported. Consistent with expression profiling results, flow cytometry analysis showed the mitotic population in RUNX1 depleted cells was significantly decreased, indicating RUNX1 is important for proper cell division. To investigate the mechanisms by which RUNX1 controls expression of those differentially expressed genes, RUNX1 genome-wide occupancy analysis (ChIP-seq) was performed in MCF10A cells. We found that although RUNX1 binding is enriched at transcription start sites (TSS), RUNX1 also binds to loci distal to TSSs and multiple other regulatory elements. Therefore, RUNX1 has the capability to utilize multiple mechanisms to control target gene expression. Our results highlight crucial roles for RUNX1 in controlling normal growth of mammary epithelial cells, consistent with its tumor suppressor activities. Loss of RUNX1 leads to improper gene regulation and cell cycle defects, which may contribute to tumor progression in breast cancer. These RUNX1-mediated mechanisms point to novel intervention strategies for early stage breast cancer.
Citation Format: Deli Hong, Andrew J. Fritz, Coralee E. Tye, Natalie A. Page, Joseph R. Boyd, Jane B. Lian, Janet L. Stein, Gary S. Stein. RUNX1 global binding and gene regulation in mammary epithelial cells revealed novel Runx1 mediated cellular activities [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 4462.
Abstract 4468: Repression of CD44 expression by p53 in a breast cancer progression model
Authors: Liu Fang , Liu Zhengxue , Wang Guannan , Roy-Kundu Tanima , Matsuura Isao 
Published: August 2018

Abstract
CD44 is an important molecule in breast cancer. Although CD44 lacks its own signaling domain, it can associate with and co-stimulate signaling by a number of growth factor receptors, such as Her2 and EGF receptor 1. Knockdown of CD44 significantly reduces mammary tumor-initiating frequency and tumor weight. Disruption of tumor cell surface CD44 function induces apoptosis in metastatic mammary carcinoma cells in vivo. Some studies showed that the breast cancer stem cells are enriched in the CD44highCD24low population. The tumor suppressor p53 is mutated or functionally inactivated in over 70% of cancer. In breast cancer, p53 is mutated in ~35% cases, and ~50% breast cancers contain MDM2 or MDMX overexpression. A previous study showed that p53 repressed the expression of CD44 and that this activity was essential for the tumor-suppressor function of p53. We find that p53 potently represses the expression of CD44 in normal human breast epithelial cells. Mutation of the p53 binding site on the CD44 promoter greatly reduces the ability of p53 to repress CD44 expression. We show that p53 repression of CD44 expression is progressively reduced in a breast cancer progression model. Our ongoing studies are elucidating the underlying mechanisms. Our findings will help for better understanding and treatment of breast cancer.
Citation Format: Fang Liu, Zhengxue Liu, Guannan Wang, Tanima Roy-Kundu, Isao Matsuura. Repression of CD44 expression by p53 in a breast cancer progression model [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 4468.
Abstract 4489: Effect of cancer-associated fibroblasts on the progression of malignant melanoma cells
Authors: Fujikawa Heishiro , Yashiro Masakazu , Hatano Takaharu , Maeda Shusaku , Motomura Hisashi 
Published: August 2018

Abstract
Introduction
Malignant solid tumor is composed of not only cancer cells but also various types of stromal cells, which include fibroblasts, vascular endothelial cells, and immune cells. Currently, it has been reported that fibroblasts in tumor stroma, namely cancer-associated fibroblasts (CAFs), might affect cancer progression. Some studies suggested that CAFs have the stimulation-activity of the malignant potential of melanoma cells, but some reports mentioned their inhibitory-activity of melanoma cells. In this study, we investigated the effects of CAFs on the proliferation and invasion ability of malignant melanoma cells.
Material and Method
We used 2 malignant melanoma cell lines, MMAc and COLO679. Three CAFs were established from sebaceous carcinoma or skin malignant melanoma. Serum-free conditioned medium (CAF-CM) from CAF was prepared as follows. CAF were seeded into 100 mm plastic dishes with 10 ml of DMEM containing 2% FCS. To obtain CAF-CM, CAF were washed by PBS and then incubated for 3 days with serum-free DMEM. The conditioned medium was collected as CAF-CM. Serum-free DMEM was used as the control. CAFs were used before the 15th passage in culture. The effect of CAF-CM on the proliferation of the melanoma cells was determined by cytometry assay using Coulter Counter. The effect of CAF-CM on the motility of the melanoma cells was examined by Matrigel-invasion assay.
Result
CAF-CM significantly increased the proliferation of melanoma cell, in compared the control. Under the condition of adding 25% of CAF-CM, the number of MMAc cells were increased about 300% after 72 hours of incubation, and 105% after 120 hours of incubation that of COLO679 increased about 56% after 72 hours of incubation, 130% after 120 hours of incubation. CAF-CM significantly increased the invasion of MMAc cells. The invasion of MMAc cells were increased about 200% after 72 hours of incubation following the addiction of 25% CAF-CM. In contrast, CAF-CM did not affect on the invasion of COLO679 cells.
Conclusion
CAFs are associated with the proliferation and invasion of malignant melanoma cells.
Citation Format: Heishiro Fujikawa, Masakazu Yashiro, Takaharu Hatano, Shusaku Maeda, Hisashi Motomura. Effect of cancer-associated fibroblasts on the progression of malignant melanoma cells [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 4489.
Abstract 4505: Silencing connexin 43 induces cell cycle entry and invasion in non-neoplastic mammary epithelial cells
Authors: Fostok Sabreen F. , Bazzoun Dana , Lelievre Sophie A. , El-Sibai Mirvat , Talhouk Rabih S. 
Published: August 2018

Abstract
Studies demonstrated loss of connexin 43 (Cx43) expression in breast cancer cells in-vitro and in-vivo. Our previous studies have shown that silencing Cx43 in HMT-3522 S1 cells, non-neoplastic human mammary epithelial cells (S1 cells), altered apical polarity and mitotic spindle orientation under 3-dimensional (3-D) culture conditions. The purpose of this study is to investigate the effects of Cx43 loss on proliferation and invasion of non-neoplastic breast epithelium. Cx43 shRNA-transfected and control S1 cells were cultured under 2-D and 3-D conditions. Cx43-knockdown S1 cells exhibited enhanced proliferation both in 2-D and 3-D throughout the culture period, as shown by the increased cell counts and acinar size, respectively. In addition, cell cycle entry was enhanced, as indicated by the increased percentages of cells in S and G2/M phases and the reduced percentage of cells in G0/G1 phase. Cx43-silenced S1 cells upregulated the expression of proliferation genes, c-Myc and cyclin D1, in 2-D and 3-D, but maintained β-catenin levels. Furthermore, immunoprecipitation studies showed that Cx43 associated with β-catenin and ZO-2 in 2-D and 3-D cultures of S1 cells, and co-localized with β-catenin in 3-D, suggesting assembly of gap junction complexes in S1 cells. The loss of Cx43 caused mis-localization of β-catenin in 3-D cultures of S1 cells, suggesting involvement of the Wnt/β-catenin pathway downstream of Cx43 signaling. β-Catenin primarily exhibited apico-lateral distribution in S1 cells and re-localized to basolateral membrane domains in Cx43 knockdown cells. Silencing Cx43 enhanced migration of S1 cells by 40%, as shown by time-lapse imaging. In addition, Cx43-silenced S1 cells exhibited loss of the characteristic spheroid morphology and acquired a migratory phenotype in acini. Matrigel-invasion and MMP-9 activity were also enhanced. Cx43-silenced S1 cells were capable of invading the matrigel by two-fold compared to control cells. This was concomitant with enhanced expression and activity levels of Rho GTPases (RhoA, Rac1 and Cdc42), suggesting that Cx43 regulates non-canonical Wnt signaling, as a mechanism to induce migration and invasion. We propose a role for Cx43 loss in triggering proliferation and invasion events in non-neoplastic breast epithelium downstream of disrupted Wnt signaling.
Citation Format: Sabreen F. Fostok, Dana Bazzoun, Sophie A. Lelievre, Mirvat El-Sibai, Rabih S. Talhouk. Silencing connexin 43 induces cell cycle entry and invasion in non-neoplastic mammary epithelial cells [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 4505.