bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5190: Detection of radioresistant gene of esophageal cancer by the new cyclopedic gene analysis with transposon
Authors: Takesue Tomoko 
Published: May 2015

Abstract
Backgound Radiation is one of the most important therapies same as operation and chemotherapy for esophageal cancer. However a rate of therapeutic effect is low, 68.3% as a chemoradiation therapy for advanced esophageal cancer in Japan. Predicting an effect before radiation therapy is impossible, many patients suffer from side effect of radiation without enough therapeutic effect. To predict and improve an effect, it is need to identify genes and mechanism of radioresistance. Aim of this research is to detect radioresistant gene of esophageal cancer by the new cyclopedic gene analysis with transposon.
Methods Transposon is a base sequence which transports to other location in the genome at random. Inserting CMV promotor to transposon as a transcriptional activator, the following gene of transported transposon is overexpressed and the gene inserted transposon is knocked down. We can get various cells which have a different overexpressed or knocked down gene by transposon method. After drug treatment or irradiation for cells inserted transposon and CMV promotor, named transposon tagged cells, survived cells have overexpressed redioresistant genes or knocked down radiosensitive genes. We can pick up candidate redioresistant genes to detect the location of transposon in survived cells. We have already succeeded to acquire candidate chemoresistant genes of breast cancer and esophageal cancer.
Results Twenty days after irradiation of 9 to 11 Gy for transposon tagged cells, survived cells became colonies. Picking up survived colonies and analyzing its gene, nine genes were detected as a candidate gene. All genes were knocked down by inserting the transposon. Knock down of candidate genes were demonstrated by decreasing an amount of mRNA in survived colonies. Cells of survived colonies also showed higher survival rate after irradiation than the rate of parent esophageal cancer cells without transposon. These results mean that knocking down of the candidate gene relates to redioresistance actually. Cytochrome c oxidase subunit 1 is one of the gene detected by transposon method. Cytochrome c oxidase 1 is known as an enzyme of Cytochrome c which induce apoptosis after DNA damage from radiation by activating caspase cascade. This fact supports that knock down of cytochrome c oxidase 1 may suppress release of cytochrome c and then radiation induced apoptosis.
Conclusion Transposon method is able to analyze resistant genes comprehensively. To reveal resistant mechanism of detected gene, new target of treatment may be found.
Citation Format: Tomoko Takesue. Detection of radioresistant gene of esophageal cancer by the new cyclopedic gene analysis with transposon. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5190. doi:10.1158/1538-7445.AM2014-5190
Abstract 5197: MiR-629 targets TRIM33 to promote TGF-β/Smad signaling in clear cell renal cell carcinoma
Authors: Jingushi Kentaro , Nakata Wataru , Ueda Yuko , Kitae Kaori , Fujita Kazutoshi , Uemura Motohide , Nonomura Norio , Tsujikawa Kazutake 
Published: May 2015

Abstract
Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney, and clear cell RCC (ccRCC) represents the most common renal histology. To identify a novel biomarker or a candidate target of molecular-targeted drug for ccRCC, we focused on miRNA expression signatures obtained from ccRCC clinical specimens by miRNA-microarray. The expression signatures revealed that miR-629 was significantly up-regulated in ccRCC specimens compared to normal specimens. Inhibition of miR-629 through a hairpin miRNA inhibitor inhibited cell migration and invasion. We found that miR-629 directly targets the Tripartite motif-containing 33 (TRIM33) an inhibitor of TGF-β/Smad signaling pathway. Inhibition of miR-629 significantly suppressed TGF-β -induced Smad activation through up-regulation of TRIM33 expression and subsequent inhibition of Smad2/3 and Smad4 binding. Furthermore, miR-629 inhibition attenuated the effect of TGF-β on expression of EMT-related factors and cell migration and invasion. Finally, in human clinical specimens, TRIM33 was down-regulated where an association with pathological stage and grade. Our findings identify miR-629 as a potent regulator of TGF-β/Smad signaling pathway and functions as an oncomir, which may provide a novel therapeutic strategy for treatment of ccRCC.
Citation Format: Kentaro Jingushi, Wataru Nakata, Yuko Ueda, Kaori Kitae, Kazutoshi Fujita, Motohide Uemura, Norio Nonomura, Kazutake Tsujikawa. MiR-629 targets TRIM33 to promote TGF-β/Smad signaling in clear cell renal cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5197. doi:10.1158/1538-7445.AM2014-5197
Abstract 5204: MicroRNA-6734 induces p21 gene expression by targeting a complementary p21 promoter sequence and inhibits colon cancer cells
Authors: Kang Moo Rim , Yun Jieun , Oh Soo Jin , Lee Chang Woo , Park Ki Hwan , Kang Jong Soon 
Published: May 2015

Abstract
MicroRNAs (miRNAs) regulate gene expression by binding to the cellular transcript leading to translational repression or degradation of the target mRNA. However, miRNA have also been shown to induce gene expression by targeting promoter in a phenomenon referred to as RNA activation (RNAa). Recently, p21 promoter targeted small activating RNA, dsP21-322, has been shown to inhibit the growth of various cancer cells. The purpose of this study was to investigate the effects of miR-6734, which has a sequence homology with dsP21-322, on p21 gene activation and cell growth inhibition in HCT116 human colon cancer cells. miR-6734 induced p21 gene expression and the induction of p21 was decreased by treatment with miR-6734-5P inhibitor or p21 siRNAs. Furthermore, single transfection of miR-6734 induced p21 gene expression for 12 days which is an interesting feature of RNAa. Knockdown experiments revealed that induction of p21 by miR-6734 required the miRNA maturation protein Ago2 and nuclear transport protein TNRC6A. Functionally, miR-6734 suppressed cellular growth initiated G0/G1 phase arrest and increased the percentage of apoptotic cells by increasing caspase-3/7 activity in dose dependent manner. In addition, miR-6734-mediated cell cycle arrest and apoptosis was significantly suppressed by miR-6734-5P inhibitor, p21 siRNAs, Ago2 siRNAs and TNRC6A siRNA. These results suggest that endogenous miRNA may facilitate RNAa in cancer for specific gene expression and manipulate cancer cell phenotype.
Citation Format: Moo Rim Kang, Jieun Yun, Soo Jin Oh, Chang Woo Lee, Ki Hwan Park, Jong Soon Kang. MicroRNA-6734 induces p21 gene expression by targeting a complementary p21 promoter sequence and inhibits colon cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5204. doi:10.1158/1538-7445.AM2014-5204
Abstract 5206: Mir-134/487b/655 cluster regulates TGF-β-induced epithelial-mesenchymal transition and drug resistance to gefitinib by targeting MAGI2 in lung adenocarcinoma cells
Authors: Seike Masahiro , Kitamura Kazuhiro , Miyanaga Akihiko , Okano Testuya , Noro Rintaro , Gemma Akihiko 
Published: May 2015

Abstract
Epithelial-mesenchymal transition (EMT) has recently been recognized as a key element of cell invasion, migration, metastasis, and drug resistance in several types of cancer, including non-small cell lung cancer (NSCLC). Our aim was to clarify microRNA (miRNA) -related mechanisms underlying EMT followed by acquired resistance to epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI) in NSCLC. MiRNA expression profiles were examined before and after TGF-β1 exposure in four human adenocarcinoma cell lines with or without EMT. Correlation between expressions of EMT-related miRNAs and resistance to EGFR-TKI gefitinib was evaluated. MiRNA array and quantitative RT-PCR revealed that TGF-β1 significantly induced overexpression of miR-134, miR-487b, and miR-655, which belong to the same cluster located on chromosome 14q32, in lung adenocarcimona cells with EMT. MAGI2, a predicted target of these miRNAs and a scaffold protein required for PTEN, was diminished in A549 cells with EMT after the TGF-β1 stimulation. Overexpression of miR-134 and miR-487b promoted the EMT phenomenon and affected the drug resistance to gefitinib, whereas knockdown of these miRNAs inhibited the EMT process and reversed TGF-β1-induced resistance to gefitinib. Our study demonstrated that the miR-134/487b/655 cluster contributed to the TGF-β1-induced EMT phenomenon and affected the resistance to gefitinib by directly targeting MAGI2, whose suppression subsequently caused loss of PTEN stability in lung cancer cells. The miR-134/miR-487b/miR-655 cluster may be new therapeutic targets in advanced lung adenocarcinoma patients, depending on the EMT phenomenon.
Citation Format: Masahiro Seike, Kazuhiro Kitamura, Akihiko Miyanaga, Testuya Okano, Rintaro Noro, Akihiko Gemma. Mir-134/487b/655 cluster regulates TGF-β-induced epithelial-mesenchymal transition and drug resistance to gefitinib by targeting MAGI2 in lung adenocarcinoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5206. doi:10.1158/1538-7445.AM2014-5206
Abstract 5216: Epigenetic characterization and specific targeting of breast cancer stem cells
Authors: Liu Huiping 
Published: May 2015

Abstract
Metastasis causes 90% of the mortality associated with solid tumors, such as breast cancer. However, the molecular mechanisms underlying metastasis remain poorly understood and no effective approaches are available to cure metastasis. The identification of cancer stem cells (CSCs), a subpopulation of cancer cells with stem cell properties, has brought us a new perspective on cancer, including leukemia and solid tumors. CSCs are proposed to mediate cancer relapse and metastasis due to their resistance to conventional therapies. Our work has demonstrated that breast cancer stem cells (BCSCs) are able to mediate spontaneous lung metastases in human-in-mouse xenograft models. We have also identified that miR-30c, a human breast tumour prognostic marker, regulates both invasion and chemo-resistance, through targeting TWF1, VIM, and downstream IL-11. TWF1 encodes an actin-binding protein and promotes epithelial-to-mesenchymal transition (EMT). An IL-6 family member, IL-11 was identified as a secondary target of TWF1 in the miR-30c signalling pathway. Expression of miR-30c inversely correlated with TWF1 and IL-11 levels in primary breast tumors and low IL-11 correlated with relapse-free survival in breast cancer patients. Our study demonstrates that miR-30c is transcriptionally regulated by GATA3 in breast tumors. Identification of a novel miRNA-mediated pathway that regulates chemo-resistance in breast cancer will facilitate the development of novel therapeutic strategies. Future ongoing interactive basic and translational research directions include: (1) to understand CSCs using cutting-edge single cell sequencing technology and functional studies; (2) to image CSCs (their dynamic behavior and interactions with immune cells and non-CSCs) during metastasis using bioluminescence imaging and intravital imaging systems; and (3) to target CSCs with novel therapeutics delivered by nanoparticles.
Citation Format: Huiping Liu. Epigenetic characterization and specific targeting of breast cancer stem cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5216. doi:10.1158/1538-7445.AM2014-5216
Abstract 5222: microRNA-148a is a prognostic oncomiR that targets MIG6 and BIM to regulate EGFR and apoptosis in glioblastoma
Authors: Kim Jungeun , Zhang Ying , Skalski Michael , Hayes Josie , Kefas Benjamin , Schiff David , Purow Benjamin , Parsons Sarah , Lawler Sean , Abounader Roger 
Published: May 2015

Abstract
In this study, we uncovered microRNA-148a (miR-148a) as a novel prognostic and oncogenic microRNA in glioblastoma (GBM). MiR-148a expression was significantly higher in human GBM tissues, cell lines and stem cells (GSCs) as compared to normal human brain and astrocytes. High miR-148a levels were a risk indicator for GBM patient survival. MiR-148a increased GBM cell and GSC growth, survival, migration, and invasion as well as GSC neurosphere formation. We identified the EGFR regulator, MIG6, and the apoptosis regulator, BIM as two direct targets of miR-148a and showed with rescue experiments that they mediate the oncogenic effects of miR-148a. Importantly, by inhibiting MIG6 expression, miR-148a reduced EGFR trafficking to the Rab7-expressing late endosome/lysosomal compartments. This coincided with a reduction of EGFR degradation and induction of EGFR expression and activation. Lastly, inhibition of miR-148a expression led to a strong inhibition of GSC and GBM xenograft growth in vivo. These findings represent the first comprehensive analysis of the role of miR-148a in GBM. They show that miR-148a expression levels are predictive of patient survival and that this microRNA enhances malignancy by inhibiting apoptosis and indirectly activating EGFR. These results also suggest that miR-148a is a potential target for GBM therapy.
Citation Format: Jungeun Kim, Ying Zhang, Michael Skalski, Josie Hayes, Benjamin Kefas, David Schiff, Benjamin Purow, Sarah Parsons, Sean Lawler, Roger Abounader. microRNA-148a is a prognostic oncomiR that targets MIG6 and BIM to regulate EGFR and apoptosis in glioblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5222. doi:10.1158/1538-7445.AM2014-5222
Abstract 5228: Characterization of miR-21 as a potential circulating biomarker for osteosarcoma
Authors: Nakka Manjula , Li Yiting , McGee Colin , Lau Ching , Man Tsz Kwong 
Published: May 2015

Abstract
MicroRNAs (miRNAs) are a class of small noncoding RNAs that are implicated in various important biological processes by regulation of gene expression. Aberrant miRNA expression is suggested to be associated with various human disorders including cancer. In this study, we studied if miRNAs can be used as biomarkers in osteosarcoma (OS). OS is the most common malignant bone tumor in children and young adults. Despite the use of surgery and multi-agent chemotherapy, OS patients who respond poorly towards chemotherapy or develop relapses have a dismal outcome. Thus, it is of clinical significance if a biomarker approach can be developed to monitor tumor burden and detect early relapses in the patients, so that they can be treated as early as possible to improve the survival. To achieve this goal, we performed miRNA profiling on a cohort of OS plasma samples collected from the Texas Children's Hospital. miR-21 and other miRNAs were identified to be elevated in OS patients relative to a group of healthy controls. Circulating miR-21 has been detected in other types of cancer and in the tumor it is known to negatively regulate tumor suppressor genes involved in proliferation, apoptosis and invasion; however, its role in OS is still unclear. Hence, we first validated that miR-21 was elevated in a set of independent osteosarcoma plasma samples but not in the control samples. Using serial plasma samples from a group of patients, we found that the circulating miR-21 level was lower in the posttreatment plasma samples than in the pretreatment samples. These results suggest that circulating miR-21 may correlate with tumor burden of the patients. In addition, miR-21 was expressed in many OS tumors as detected by in situ hybridization on an OS tissue microarray. When tested on two OS cell lines, miR-21was significantly increased in the culture media between 24 and 48 hours after plating in a cell number dependent manner, suggesting that miR-21 could be released from the tumor cells. Taken together, our results suggest that miR-21 is expressed in OS and its level in plasma may reflect tumor burden in OS patients.
Citation Format: Manjula Nakka, Yiting Li, Colin McGee, Ching Lau, Tsz Kwong Man. Characterization of miR-21 as a potential circulating biomarker for osteosarcoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5228. doi:10.1158/1538-7445.AM2014-5228
Abstract 523: Detection of PIWI-piRNAS in the mitochondria of human normal and cancer cells
Authors: Kwon ChangHyuk , Tak Hyosun , Rho Mina , Chang Hae Ryung , Km Yon Hui , Kim Kyung Tae , Lee Eun Kyung , Balch Curt , Nam Seungyoon 
Published: May 2015

Abstract
Piwi-interacting RNAs (piRNAs) are a class of small non-coding RNAs that regulate differentiation in primordial germ cells, found mainly in the nucleus and cytoplasm. However, despite the essentiality of mitochondria to intrinsic apoptosis and energy metabolism, the presence of piRNAs (and their associated Piwi proteins) in this organelle remains largely unknown. In this study, a public database comparison of mitochondrial RNA-seq data from human normal (HEK293) and cancer (HeLa and 143B) cells revealed the presence of 29 mature piRNA sequences, with 12 of those piRNA sequences perfectly matching 7 tRNAs (Phe, Val, Leu, His, Ser, Glu, and Thr), suggesting piRNAs and tRNAs derive from a common precursor mitochondrial polycistronic transcript. Consistent with their known interaction with piRNAs, further examination revealed the presence of PIWI proteins in mitochondria. Moreover, the majority of the 29 piRNA sequences overlapped multiple longer sequences (expressed sequence tags, ESTs) that uniquely mapped to the mitochondrial genome. To our knowledge, this is the first report of Piwi and piRNAs in the mitochondria of mammalian normal and cancer cells.
Citation Format: ChangHyuk Kwon, Hyosun Tak, Mina Rho, Hae Ryung Chang, Yon Hui Km, Kyung Tae Kim, Eun Kyung Lee, Curt Balch, Seungyoon Nam. Detection of PIWI-piRNAS in the mitochondria of human normal and cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 523. doi:10.1158/1538-7445.AM2014-523
Abstract 5236: Identification of miR-888 as the first miRNA cancer-testis antigen
Authors: Hovey Adriann M. , Devor Eric J. , Dai Donghai , Leslie Kimberly K. 
Published: May 2015

Abstract
Cancer-testis (CT) antigens are a large family of genes that are exclusively expressed in human testes and are typically located on the X chromosome and part of multicopy gene families. Importantly, CT antigens are overexpressed in a variety of tumors. To date, all known CT antigens are protein-coding genes. Here we identify miR-888 as the first miRNA with features characteristic of a CT antigen. In a panel of 21 normal human tissues, miR-888 expression was high in testes, but minimal or absent in all other tissues. Analysis of cancer cell lines demonstrated expression of miR-888 in endometrial cancer cells, but not in choriocarcinoma, breast, ovarian or prostate cancer cells. In endometrial patient tumor specimens, miR-888 was 8-fold overexpressed relative to benign endometrium (p &lt; 0.01). In addition, expression of miR-888 was highest in endometrial carcinosarcomas (fold change = 22, p &lt; 0.01), a rare and aggressive type of endometrial tumor. Analysis of The Cancer Genome Atlas database revealed that miR-888 expression is significantly associated with high stage and grade endometrial tumors, which has also been observed for many other CT antigens. Furthermore, the miR-888 gene is part of a multicopy gene family on the X chromosome and evolved recently in primates through gene duplication. Therefore, we classify miR-888 as the first miRNA CT antigen and hypothesize that other miRNAs located on the X chromosome may also function as CT antigens. These findings have the potential to advance understanding of cancer-testis genes, their evolution and what role they play in testis and cancer biology.
Note: This abstract was not presented at the meeting.
Citation Format: Adriann M. Hovey, Eric J. Devor, Donghai Dai, Kimberly K. Leslie. Identification of miR-888 as the first miRNA cancer-testis antigen. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5236. doi:10.1158/1538-7445.AM2014-5236