bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5239: MiR-148a promotes apoptosis in urothelial cell carcinoma of the bladder cells in part by targeting DNMT1
Authors: Lombard Alan , Mooso Ben , Libertini Steve , Lim Rebecca , Costanzo Nicole , Ghosh Paramita , Mudryj Maria 
Published: May 2015

Abstract
Introduction: MiRNAs are now recognized as major players in cancer. MiR-148a has been shown to be a tumor suppressor in the context of several cancers including prostate, gastric, and lung but a study investigating its role in bladder cancer has never been performed. Here we characterized the expression and role of miR-148a in bladder cancer.
Methods: Real time PCR was used to assess the levels of miR-148a across several bladder cancer cell lines. MiR-148a mimics were employed in T24 and UM-UC-3 cells to assess proliferation by CCK-8 proliferation assay, colony formation assay, and flow cytometry. Mimics were also used to assess apoptosis by immunoblot and annexin-V staining coupled to flow cytometry. Immunoblot was used to probe for targets of miR-148a and siRNA was used to knock-down DNMT1 to phenocopy miR-148a treatment results. CCK-8 proliferation assays and crystal violet staining were used to assess the additive effects of miR-148a with either cisplatin or doxorubicin on T24 and UM-UC-3 cells and CCK-8 proliferation assays were also used to assess the role DNMT1 plays in cisplatin sensitivity.
Results: All bladder cancer cell lines had significantly reduced expression of miR-148a than that of a control immortalized urothelial cell line. MiR-148a mimic treatment of T24 and UM-UC-3 cells led to large decreases in viability. Flow cytometry demonstrated an increase in S-phase and no major G1 or G2/M arrests in miR-148a mimic treated cells versus control oligo treated cells suggesting that the effects observed on viability were due to increased apoptosis. Immunoblots for cleaved caspase-3 and cleaved PARP along with annexin-V staining coupled to flow cytometry showed as expected a strong induction of apoptosis in miR-148a mimic treated cells. Immunoblots demonstrated that miR-148a targets DNMT1 and DNMT1 knock-down was able to partially phenocopy results from miR-148a mimic treatment suggesting DNMT1 is downstream of miR-148a. Finally, we found that miR-148a can be used with either cisplatin or doxorubicin for an additive effect in inducing apoptosis and that DNMT1 targeting is involved in sensitivity to cisplatin.
Conclusions: Our work demonstrates for the first time that miR-148a plays a tumor suppressive role in bladder cancer and suggests it could be used as a novel therapeutic agent either alone or in conjunction with chemotherapeutics.
Citation Format: Alan Lombard, Ben Mooso, Steve Libertini, Rebecca Lim, Nicole Costanzo, Paramita Ghosh, Maria Mudryj. MiR-148a promotes apoptosis in urothelial cell carcinoma of the bladder cells in part by targeting DNMT1. [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 5239. doi:10.1158/1538-7445.AM2014-5239
Abstract 5245: A network of microRNAs contolled by oncogenic B-Raf signaling in melanoma cells
Authors: Couts Kasey L. , Anderson Emily M. , Gross Maren M. , Sullivan Kevin , Ahn Natalie G. 
Published: May 2015

Abstract
Constitutive activation of the B-Raf/MKK/ERK signaling pathway a result of B-Raf activating mutations is a hallmark of over two-thirds of melanomas. The most prevalent mutation, B-RafV600E, promotes cancer cell behavior through mechanisms which are still incompletely defined. We utilized microRNA (miRNA) microarray profiling to identify a network of more than 20 miRNAs deregulated by B-Raf/MKK/ERK in melanoma cells, the majority of which modulate expression of key cancer regulatory genes and functions. Importantly, miRNAs within the network converge on protein regulation and cancer phenotypes, suggesting that these miRNAs might function combinatorially. Additionally, by altering functional levels of these miRNAs in cells with miRNA mimics and inhibitors we demonstrate that miRNAs augment effects on protein repression and cell invasion when co-expressed, and we also observe gene-specific latency and interference effects between miRNAs. Thus, B-Raf/MKK/ERK controls key aspects of cancer cell behavior and gene expression by modulating a network of miRNAs with cross-regulatory functions. The findings highlight the potential for complex interactions between coordinately regulated miRNAs within a gene expression network.
Citation Format: Kasey L. Couts, Emily M. Anderson, Maren M. Gross, Kevin Sullivan, Natalie G. Ahn. A network of microRNAs contolled by oncogenic B-Raf signaling in melanoma 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 5245. doi:10.1158/1538-7445.AM2014-5245
Abstract 5246: The role of mir-21 and Let-7a in HMGA2 associated colorectal cancer pathogenesis with different APC/k-ras status
Authors: Cheng Ya-Wen , Chen I-Chien 
Published: May 2015

Abstract
Colorectal cancer (CRC) is one of the leading causes of cancer death in both the Western world and Taiwan. Although CRC can be inherited, most CRCs are sporadic. The possible causes of colorectal cancer include a high fat diet, low fiber intake, obesity and sedentary lifestyle. A relatively limited number of oncogenes and tumor-suppressor genes_most prominently the APC, KRAS, and p53 genes are mutated in a sizeable fraction of CRCs. Even though numerous genes have been reported to be associated with tumorigenesis in CRC, only a few of them have been validated and used as biomarkers for predicting metastasis and treatment response in clinical applications. Our published paper showed that overexpression of high-mobility group AT-hook 2 (HMGA2) is associated with metastasis and unequivocally occurred in parallel with reduced survival rates of patients with CRC, and thus HMGA2 may potentially serve as a biomarker for predicting aggressive CRC with poor survivability and as an indicator of better response to radiotherapy. The Let-7a miRNA is a tumor suppressing miRNA that targets oncogenes, including HMGA2. Previous reports show that Let-7a miRNA may regulate miR-21 expression in cholesteatoma. The benign nature of cholesteatoma may be due to a balance between Let-7a and miR-21. The miR-21 has oncogene-like activity and is highly expressed in several types of cancers. Our present study also found that patients with high miR-21 expression had poor survival. In this study, we demonstrated the association of mir-21 and Let-7a in HMGA2 regulation in the pathogenesis of colorectal cancer and how the expression of these genes is associated with the clinical outcomes and radiotherapy response of CRC patients.
Citation Format: Ya-Wen Cheng, I-Chien Chen. The role of mir-21 and Let-7a in HMGA2 associated colorectal cancer pathogenesis with different APC/k-ras status. [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 5246. doi:10.1158/1538-7445.AM2014-5246
Abstract 5256: Mechanism of field cancerization
Authors: Czerniak Bogdan A. , Lee Sangkyou , Bondaruk Jolanta , Lee Sooyong , Majewski Tadeusz , Zhang Shizhen , Shen Li , Liu Yuexin , Guo Charles , Dinney Colin , Grossman H. Barton , Zhang Wei , Bar-Eli Menashe , Baggerly Keith , Behringer Richard , McConkey David , McConkey David , Knowles Margaret , Chung Woonbok , Issa Jean-Pierre 
Published: May 2015

Abstract
We developed a strategy that combines histologic and genetic mapping that permits interrogation of the chronology of genetic changes associated with cancer development on a whole-organ scale. By using this approach, we analyzed the sequence of genetic alterations contiguous to the tumor suppressor RB1 and identified a set of alternative target genes that we term “forerunner” (FR) genes whose silencing was associated with development of clonal plaque-like mucosal field effects initiating bladder carcinogenesis.
Expression and methylation studies identified five candidate FR genes (ITM2B, LPAR6, MLNR, CAB39L, and ARL11). In vitro mechanistic studies demonstrated that three of these genes (ITM2B, LPAR6 and ARL11) control cell survival and proliferation consistent with their loss of function being contributory to tumorigenesis, and in vivo genetic ablation of Lpar6 in a mouse model resulted in activation of basal/stem cell transcriptional programs involving STAT3 and NFκB causing proliferative expansion of the basal layer of the urothelium. Whole genome analyses of the field effects in a representative whole-organ map revealed a sequential accumulation of alterations in RHO/RAC/Cdc42 pathways that control invasion and cell motility.
These studies identify FR genetic alterations in tissue fields as one of the earliest events in carcinogenesis and provide comprehensive description of field cancerization in a primary human tumor. The results have important implications for the development of novel detection markers and chemoprevention therapeutic strategies.
Citation Format: Bogdan A. Czerniak, Sangkyou Lee, Jolanta Bondaruk, Sooyong Lee, Tadeusz Majewski, Shizhen Zhang, Li Shen, Yuexin Liu, Charles Guo, Colin Dinney, H. Barton Grossman, Wei Zhang, Menashe Bar-Eli, Keith Baggerly, Richard Behringer, David McConkey, David McConkey, Margaret Knowles, Woonbok Chung, Jean-Pierre Issa. Mechanism of field cancerization. [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 5256. doi:10.1158/1538-7445.AM2014-5256
Abstract 5258: Overexpressed TYRO3 in colorectal cancer regulates tumorigenesis and metastasis
Authors: Chien Chun Wei , Lai Yen-Yu , Lin Bo-Wen , Lin Shao-Chieh , Lee Jenq-Chang , Tsai Shaw-Jenq 
Published: May 2015

Abstract
Colon cancer is a multiple-step disease with less 10% survival rate at late stage. To achieve improvement of colon cancer therapy, we aim to find novel oncogenes that contribute to colon cancer progression. By our in-house bioinformatic tool prediction, we identified TYRO3 to be a potential oncogene. TYRO3, a receptor tyrosine kinase, was reported to be overexpressed in melanoma via genomic screening; however, its role in cancer initiation, progression, and malignancy remains largely unknown. Herein, we showed that compared to normal colon tissue, TYRO3 is overexpressed in polyps and colon cancer tissue. The expression level in colon cancer is significantly associated with cancer malignancy. Overexpression of TYRO3 increased cell proliferation, motility, and anchorage-independent colony formation in vitro. Furthermore, we confirmed TYRO3 tumorigenic potential by xenograft model and metastatic assay in vivo. To investigate novel mechanisms mediated by TYRO3, we performed next generation sequencing (RNS-seq) to identify genes that were upregulated under TYRO3 overexpression. Results showed that TYRO3 significantly enriched genes involved in epithelial-mesenchymal transition and tumorigenesis, which is consistent with our hypothesis and finding. Taken together, these data provide evidence to support that TYRO3 plays an important role in malignant process of colon cancer progression likely through its novel functions in the nucleus.
Citation Format: Chun Wei Chien, Yen-Yu Lai, Bo-Wen Lin, Shao-Chieh Lin, Jenq-Chang Lee, Shaw-Jenq Tsai. Overexpressed TYRO3 in colorectal cancer regulates tumorigenesis and metastasis. [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 5258. doi:10.1158/1538-7445.AM2014-5258
Abstract 5261: Aberrant expression of HDAC6 sustains malignant progression by preventing epidermal growth factor receptor degradation in gastric cancer
Authors: Park Se Jin , Bae Hyun Jin , Eun Jung Woo , Shen Qinngyu , Kim Hyung Seok , Shin Woo Chan , Park Won Sang , Lee Jung Young , Nam Suk Woo 
Published: May 2015

Abstract
Cytoplasmic deacetylase, histone deacetylase 6 (HDAC6) is a critical component of the lysomal protein degradation pathways. HDAC6 has been shown to be involved in carcinogenic transformation and to modulate the epithelial-mesenchymal transition in several cancers by way of the regulations of several critical cellular functions, but the biological roles in gastric carcinogenesis remains to be elucidated. In this study, we observed that HDAC6 is aberrantly over-expressed in a subset of gastric cancer, and that targeted-inactivation of HDC6 caused cell cycle and cell death pathways-independent growth inhibition. Additional experiments evidenced that ectopic overexpression of HDAC6 sustains epidermal growth factor receptor (EGFR) degradation in EGF-stimulated gastric cancer cells. In addition, we found that HDAC6 inactivation recovered rabaptin 5, a Rab5 interacting protein potentiating Rab5, a small GTPase that regulates early endocytic events. These findings suggest that aberrant overexpression of HDAC6 confers gastric cancer cells to sustain EGF-signaling by retardation of EGFR degradation by way of repression of rababtin-5, and HDAC6 is a bona fide target for therapeutic intervention in gastric cancers.
Note: This abstract was not presented at the meeting.
Citation Format: Se Jin Park, Hyun Jin Bae, Jung Woo Eun, Qinngyu Shen, Hyung Seok Kim, Woo Chan Shin, Won Sang Park, Jung Young Lee, Suk Woo Nam. Aberrant expression of HDAC6 sustains malignant progression by preventing epidermal growth factor receptor degradation in gastric cancer. [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 5261. doi:10.1158/1538-7445.AM2014-5261
Abstract 5262: Activating transcription factor 4 regulates RET autophosphorylation and ubiquitin-dependent degradation
Authors: Bagheri-Yarmand Rozita , Cote Gilbert J. , Gagel Robert F. 
Published: May 2015

Abstract
RET proto-oncogene, a receptor tyrosine kinase (RTK), activates a complex network of signal transduction pathways that when unregulated contributes to cell transformation. Germ line missense mutations, which give rise to constitutively active oncogenic RET, were found to cause multiple endocrine neoplasia type 2 (MEN2), a dominant inherited cancer syndrome that affects multiple neuroendocrine organs. Recent findings also suggest that impairment of RTK down-regulation or deactivation may be involved in tumorigenesis. The molecular mechanism that functions to attenuate RET signaling remain elusive. ATF4 is a central mediator of integrated stress response pathway. Activation of ATF4 results in tumor cell death under stress conditions thereby suggesting that ATF4 agonists constitute a potential therapeutic strategy for inhibiting tumor growth. Here, we report that ATF4 overexpression in medullary thyroid cancer cells harboring RET C634W mutation decreases RET protein expression but not the mRNA levels. In addition, ATF4 accelerates RET turnover and promotes its ubiquitination. Moreover, a RET kinase dead mutant is more stable than wild type or M918T RET suggesting that kinase activity is required for ATF4-mediated degradation. Finally, ATF4 depletion upregulates RET protein levels and RET autophosphorylation. Our findings unravel ATF4 as a feedback negative attenuator of RET signaling that could be used as a potential therapeutic target for medullary thyroid cancer or other malignancy with RET abnormalities.
Citation Format: Rozita Bagheri-Yarmand, Gilbert J. Cote, Robert F. Gagel. Activating transcription factor 4 regulates RET autophosphorylation and ubiquitin-dependent degradation. [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 5262. doi:10.1158/1538-7445.AM2014-5262
Abstract 5275: βII-spectrin(SPTBN1) suppresses tumor progression by inhibiting Wnt signaling via kallistatin in hepatocellular carcinoma
Authors: Zhi Xiuling , Lin Ling , Shivapurkar Narayan Shivapurkar , Marshall John L. , Johnson Lynt , He Aiwu R. 
Published: May 2015

Abstract
βII-spectrin(SPTBN1, β2SP), the most common nonerythrocytic member of the β-spectrin gene family, functions as an adapter protein for Smad3/Smad4 complex formation during TGF-β signal transduction, and is required for EMT during embryonic liver development. Moreover, β2SP is emerging as a tumor suppressor. We have reported that Loss of β2SP enhances the stem-like traits and invasiveness of HCC cells. The canonical Wnt pathway, known to be a critical regulator of self-renewal in stem cell, is also constitutively activated and implicated in the induction of EMT in cancer. Kallistatin (a serine protease inhibitor, SERPINA4), which was identified as a unique inhibitor of the Wnt pathway, is expressed primly in the liver. In this study, we investigated the mechanism by which β2SP influences stem cell traits and aggressive behavior of HCC cell lines. We found that cells with decreased β2SP have decreased β-catenin phosphorylation and increased β-catenin nuclear localization, indicative of activation of Wnt signaling. Furthermore, loss of β2SP results in the decease of Kallistatin expression, the Wnt inhibitor. Restore of kallistatin reversed the Wnt activation in HCC cells from decreased β2SP level. Our study provides evidence for the first time that loss of β2SP activates Wnt signal through suppressing kallistatin expression.
Note: This abstract was not presented at the meeting.
Citation Format: Xiuling Zhi, Ling Lin, Narayan Shivapurkar Shivapurkar, John L. Marshall, Lynt Johnson, Aiwu R. He. βII-spectrin(SPTBN1) suppresses tumor progression by inhibiting Wnt signaling via kallistatin in hepatocellular 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 5275. doi:10.1158/1538-7445.AM2014-5275
Abstract 5284: SSU72 functions as a gatekeeper monitoring for chromosome integrity in mammals
Authors: Kim Se-Hyuk , Jeon Yoon , Kim Hyun-Soo , Lim Han-Jeong , Lee Ho , Lee Chang-Woo 
Published: May 2015

Abstract
Ssu72 has been initially identified as a protein phosphatase in yeast. It is becoming increasingly clear that Ssu72 plays a major modifier in regulating the transcriptional dynamics through the dephosphorylation (hypophosphorylation) of RNA polymerase II C-terminal domain. Despite these intriguing reports, the physiological function of SSU72 remains unknown particularly in higher eukaryotes. Recently, We have reported that Ssu72 functions as a cohesin-binding phosphatase in regulating sister chromatid cohesion. In addition, we generated the SSU72 conditional knock-out mice, and identified that SSU72 requirement for monitoring hepatic chromosome ploidy and hepatic damage responses in mammals. Furthermore, this study includes the physiology of SSU72 loss-of-function and the novel molecular lesions caused by SSU72 loss in vitro and in vivo.
Citation Format: Se-Hyuk Kim, Yoon Jeon, Hyun-Soo Kim, Han-Jeong Lim, Ho Lee, Chang-Woo Lee. SSU72 functions as a gatekeeper monitoring for chromosome integrity in mammals. [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 5284. doi:10.1158/1538-7445.AM2014-5284
Abstract 529: nc886, a noncoding RNA of anti-proliferative role, is suppressed by CpG DNA methylation in human gastric cancer
Authors: Park Jong-Lyul , Kim Yong Sung , Kim Seon-Young , Lee Kwang Soo , Jeon Sung H. , Lee Kwanbok , Lee Yong Sun 
Published: May 2015

Abstract
nc886, a novel type of non-coding RNA, was initially identified as a microRNA precursor or a vault RNA, but it has been shown to be distinct from them and rather to be a cellular RNA ligand and inhibitor of PKR (Protein Kinase RNA-activated). PKR's roles in viral infection, cellular stresses, and cancer are well documented. nc886 has also been suggested to be a tumor suppressor, mainly inferred by its expression pattern as well as its genomic location at human chromosome 5q31, a locus for a tumor suppressor gene(s).
Here we have investigated nc886 in gastric cancer where its expression is suppressed due to CpG DNA hypermethylation at its promoter region in a cohort of paired tumor/normal tissues from 88 gastric cancer patients and a battery of gastric cell lines. CpG hypermethylation of nc886 and thus its diminished expression is significantly associated with poor survival in these cancer patients. nc886 inhibits cell proliferation when ectopically expressed in gastric cancer cells. nc886's tumor suppressive role is corroborated by the induction of well-known oncogenes such as FOS, NF-κB, and MYC upon nc886 knockdown. All these activities of nc886 are undoubtedly independent of mature microRNA or vault RNA, but presumably through PKR that is typically activated by viral infection and cellular stresses upon which those oncogenes are known to be induced. Our data indicate that nc886 is a tumor suppressor and could potentially be used as a diagnostic marker and a therapeutic agent in gastric cancer.
Citation Format: Jong-Lyul Park, Yong Sung Kim, Seon-Young Kim, Kwang Soo Lee, Sung Ho Jeon, Kwanbok Lee, Yong Sun Lee. nc886, a noncoding RNA of anti-proliferative role, is suppressed by CpG DNA methylation in human gastric cancer. [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 529. doi:10.1158/1538-7445.AM2014-529