bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5318: The breast epithelial stem cell line D492 overexpressing miR200c-141 is resistant to mesenchymal transition.
Authors: Hilmarsdottir Bylgja , Sigurdsson Valgardur , Bergthorsson Jon T. , Sigridur Franzdottir R. , Magnus Magnusson K. , Gudjonsson T 
Published: August 2014

Abstract
MicroRNAs (miRs) are highly conserved, small RNA molecules that regulate key biological processes. miRs can act as tumor suppressors or oncogenes and their expression is often deregulated in cancers. The miR200 family is found in two clusters at chromosome 1 (miR200ba-429) and 12 (miR200c-141). Downregulation of the miR200 family has been linked to epithelial to mesenchymal transition (EMT) and recent studies show that members of this family are regulators of epithelial integrity in many tissues. We have recently shown that D492, a breast epithelial cell line with stem cell properties which generates branching structures when cultured in reconstituted basement membrane (rBM), undergoes EMT in coculture with endothelial cells. This is evidenced by formation of a stable spindle-like phenotype, suppression of keratin expression and cadherin switch from E- to N-cadherin (Sigurdsson et al. PLoS ONE 2011). In this study we have mapped the miRNA expressional changes in D492 compared to its mesenchymal-derivative D492M. Among the most profound changes were suppression of the miR200 family. Treatment of D492M with the demethylating agent 5-aza-2′-deoxycytidine reversed the EMT phenotype and reestablished E-cadherin expression. Bisulfite sequencing showed that the promoter region of miR200c-141 was methylated in D492M but not in D492. No methylation was seen in the promoter regions of E-cadherin or miR200ba-429 in either cell line. Overexpression of miR200c-141 in D492M reversed the EMT phenotype resulting in loss of N-cadherin and Snail expression and gain of E-cadherin and EpCAM expression. Interestingly, overexpression of miR200c-141 in D492M failed to reverse keratin expression back to an epithelial phenotype. When cultured in rBM D492M-200c-141 cells form irregular branching and showed no EMT phenotype. Interestingly, overexpression of miR200c-141 in D492M and D492 inhibits endothelial induced mesenchymal transition in rBM. This indicates that silencing of the miR-200c-141 with promoter methylation is associated with endothelial induced-EMT. In conclusion, our data suggests that overexpression of miR-200c-141 in D492 and D492M inhibits and reverses EMT, respectively, and this support the view that miR200c-141 may be a potent tumor suppressor and important regulator of epithelial integrity in the human breast.
Citation Format: Bylgja Hilmarsdottir, Valgardur Sigurdsson, Jon T. Bergthorsson, Franzdottir R. Sigridur, Magnusson K. Magnus, T Gudjonsson. The breast epithelial stem cell line D492 overexpressing miR200c-141 is resistant to mesenchymal transition. [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 5318. doi:10.1158/1538-7445.AM2013-5318
Abstract 532: Differential expression of FGFR-1 and -2 in hormone responsive and resistant murine mammary carcinomas.
Authors: Sahores Ana , Guillardoy Tomás , Wargon Victoria , Lanari Claudia , Lamb Caroline 
Published: August 2014

Abstract
Fibroblast growth factor (FGF) receptors (FGFRs) are dysregulated in a number of developmental and neoplastic conditions. In human breast cancer samples we have previously demonstrated a significant association between FGFR2 expression and estrogen receptors as well as a positive correlation of FGFR1 and high histological grade. Most breast carcinomas that express hormone receptors respond initially to an endocrine therapy, but over time, they develop resistance (acquired hormone resistance). Others fail to respond from the beginning (constitutive resistance). Using a breast cancer mouse model, we have previously demonstrated that antiprogestin-responsive tumors (C4-HI) show a higher expression level of progesterone receptor isoform A than PR isoform B (PRB), while tumors with constitutive (C4-2-HI) or acquired resistance (C4-HIR) to antiprogestins, display a higher expression level of PRB. Moreover, we have demonstrated, in an antiprogestin-responsive tumor that FGFR2 activated by FGF2 released by the stromal compartment participate in tumor growth activating PR. The aim of this study is to investigate the expression of FGF2, FGFR1, FGFR2 in C4-HI, C4-HIR and C4-2-HI tumor variants. By immunohistochemistry and western blot we observed a decrease in FGFR2 expression for C4-2-HI (p&lt;0.001) and C4-HIR (p&lt;0.01) as compared to C4-HI. Moreover, we found an increased expression of FGF2 and FGFR1 by western blot (p&lt;0.05) and immunohistochemistry in the epithelium of the resistant tumor variants. Similar results were obtained with another family of antiprogestin responsive and unresponsive tumors (59-HI and 59-2-HI). These data suggest that in this mammary tumor model hormone resistance may be characterized by a switch from paracrine to autocrine FGF2 signaling together with a decrease in FGFR2 and an increase in FGFR1. These results contribute to understand the role of the FGFR pathway in hormone resistance and support the use of FGFR inhibitors combined with hormonal therapy to delay the onset of hormone resistance.
Citation Format: Ana Sahores, Tomás Guillardoy, Victoria Wargon, Claudia Lanari, Caroline Lamb. Differential expression of FGFR-1 and -2 in hormone responsive and resistant murine mammary carcinomas. [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 532. doi:10.1158/1538-7445.AM2013-532
Abstract 5324: MicroRNA-23b contributes to stem cell overpopulation in colon carcinomas.
Authors: Viswanathan Vignesh , Opdenaker Lynn , Boman Bruce 
Published: August 2014

Abstract
How stem cell (SC) overpopulation drives colorectal cancer (CRC) development and growth is unclear. Because microRNAs (miRNAs) normally regulate SC populations, we reasoned that aberrant expression of these miRNAs are involved in CRC. Our goal was to identify such miRNAs. We hypothesized that there is a miRNA expression signature for SCs in the normal colonic crypt and that these miRNAs are aberrantly expressed in colon cancer SCs (CSCs). Accordingly, we used a 368-gene microarray chip to identify miRNAs that show differential expression in the crypt bottom (the SC niche) vs. the crypt top. A subset of 16 miRNAs were found to be significantly (p &lt; 0.05) over- or under-represented in the crypt bottom. Four of the 16 - hsa-mir-206, hsa-mir-7, hsa-mir-25, hsa-mir-23b -were differentially expressed in CRC vs. normal colonic epithelium. Computational target prediction analysis indicated that miR-23b targets mRNAs encoding colon SC-specific markers (ALDH1, LGR5 and LRIG1). MicroRNA-23b was down-regulated in the crypt bottom and upregulated in ALDH+ (vs. ALDH-) cells isolated from HT29 and SW480 CRC lines. Manipulation of miR-23b levels (using a precursor construct) in these cell lines decreased proliferation by causing G0/G1 cell-cycle growth arrest (vice versa with the anti-miR-23b construct). Decreasing miR-23b levels in HT29 cells inhibited their colony and colonosphere-formation ability, indicating that miR-23b has a role in CSC self-renewal. Thus, miR-23b appears to be expressed at low levels in normal colonic SCs; when upregulated in CSC, it appears to contribute to CSC overpopulation and CRC development. Targeting miR-23b may represent an innovative approach to target CSC overpopulation in CRC treatment.
Citation Format: Vignesh Viswanathan, Lynn Opdenaker, Bruce Boman. MicroRNA-23b contributes to stem cell overpopulation in colon carcinomas. [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 5324. doi:10.1158/1538-7445.AM2013-5324
Abstract 5328: MicroRNA-181a suppresses salivary adenoid cystic carcinoma metastasis by targeting the ERK/Slug pathway.
Authors: He Qianting , Zhou Xiaofeng , Li Su , Chen Zhujian , Chen Dan , Cai Yuchen , Liu Zhonghua , Zhao Tingting , Wang Anxun 
Published: August 2014

Abstract
MicroRNA deregulation plays a major role in the initiation and progression of many cancers. The objective of this study is to evaluate the role of miR-181a in the metastasis of salivary adenoid cystic carcinoma (SACC). We identified a panel of differentially expressed microRNAs in two pairs SACC cell lines with different metastatic potential using microarrays. Among these differentially expressed microRNAs, the down-regulation of miR-181a was further validated by quantitative RT-PCR. Functional analysis indicated that miR-181a inhibits SACC cell migration, invasion and proliferation in vitro and in vivo. Ectopic transfection of miR-181a inhibited the expression of NGF, VEGF, TGFβ2, ERK1/2, pERK1/2 and Slug in SACC-LM cells which had higher expression of these genes compared to SACC-83 cells; while inverse results were found in miR-181a LNA transfected SACC-83 cells. The direct targeting of miR-181a to the Slug and ERK2 mRNAs were confirmed by luciferase reporter gene assays. SiRNA-mediated knockdown of Slug, ERK2 led to reduced cell migration and invasion of SACC, and knockdown of ERK2 suppresses the expression of Slug. Taken together, these results suggest that microRNA deregulation (i.e., down-regulation of miR-181a) contributes to the metastasis of SACC. MiR-181a-mediated suppression of SACC metastasis may be achieved in part by directly targeting Slug and ERK2 and regulating ERK/Slug pathway.
Citation Format: Qianting He, Xiaofeng Zhou, Su Li, Zhujian Chen, Dan Chen, Yuchen Cai, Zhonghua Liu, Tingting Zhao, Anxun Wang. MicroRNA-181a suppresses salivary adenoid cystic carcinoma metastasis by targeting the ERK/Slug pathway. [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 5328. doi:10.1158/1538-7445.AM2013-5328
Abstract 533: Differential expression of IGF-II in Vietnamese women in triple negative breast cancer is dependent on biallelic or monoallelic IGF-II with ApaI SNP.
Authors: Radhakrishnan Vinodh Kumar , Tan Qianwei , De León Marino A. , De León Daisy D. 
Published: August 2014

Abstract
Triple negative breast cancer (TNBC) is more likely to be advanced, poorly differentiated, larger, and present in women of younger age and of lower socioeconomic status. Moreover, TNBC patients have worse outcomes when treated with currently available adjuvant chemotherapy. We have demonstrated that Breast cancer (BC) tumors from AA patients express significantly higher levels of IGF-II compared to Caucasian women (CA), and show a higher activation of the IGF signaling pathways in tumors progression (Kalla et.al., 2010). Thus we designed a study in younger Vietnamese women where TNBC incidence is increasing. A total of 24 paired BC samples were analyzed by gDNA PCR for IGF-II Apa I polymorphism to correlate with IGF-II mRNA and protein levels. The levels of IGF-II correlated with the imprinting status, i.e., Biallelic (BA; n=14)&gt;&gt;, Monoallelic with SNP (MAS; n=5)&gt;, and Monoallelic non-ApaI SNP (MA; n=5)&gt;. Higher IGF-II levels were expressed in tumor as compared to normal BC tissue samples. The free proIGF-II protein and mRNA levels were higher in biallelic tumor tissues as compared to the proIGF-II levels detected in monoallelic tumor samples. The growth factor receptors; Insulin receptor A (IRA), Insulin receptor B (IRB), Vascular endothelial growth factor receptor (VEGFR), Estrogen receptor-1 (ESR1), Progesterone receptor (PGR) and Human epidermal growth factor receptor (ERBB2) levels were determined to show if IGF-II monoallelic or biallelic dosage regulated the receptor levels. We conclude that biallelic IGF-II expression in TNBC tumors results in higher IGF-II mRNA, protein and related receptors levels than in monoallelic samples.
Citation Format: Vinodh Kumar Radhakrishnan, Qianwei Tan, Marino A. De León, Daisy D. De León. Differential expression of IGF-II in Vietnamese women in triple negative breast cancer is dependent on biallelic or monoallelic IGF-II with ApaI SNP. [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 533. doi:10.1158/1538-7445.AM2013-533
Abstract 5331: A novel function of p21 in inhibition of epithelial-mesenchymal transition through microRNAs.
Authors: Li Xiao L. , Hara Toshifumi , Choi Youngeun , Subramanian Murugan , Francis Princy , Bilke Sven , Walker Robert L. , Pineda Marbin , Yang Yu-an , Luo Ji , Wakefield Lalage M. , Park Ben H. , Brabletz Thomas , Chowdhury Dipanjan , Meltzer Paul S. , Lal Ashish 
Published: August 2014

Abstract
The tumor suppressor p21 inhibits cell proliferation during the stress response. However, p21 can also directly regulate gene expression by repressing specific transcription factors. Here, we identified p21-regulated miRNAs by sequencing small RNAs from HCT116-p21+/+ and HCT116-p21-/- cells. Three abundant clusters, miR-200b-200a-429, miR-200c-141 and miR-183-96-182 were down-regulated in p21-depleted HCT116 and MCF10A cells. Loss of p21 induced epithelial-mesenchymal transition (EMT) and enhanced migration and invasion in multiple model systems. Identification of genome-wide targets of the miR-183-96-182 cluster indicated that miR-183 and miR-96 repressed common targets, including SLUG, ZEB1, ITGB1 and KLF4, to inhibit EMT, migration and invasion. In turn, elevated ZEB1 levels in HCT116-p21-/- cells directly repressed miR-183-96-182 cluster transcription, revealing a feedback loop. Re-introduction of miR-200, miR-183 or miR-96 in HCT116-p21-/- cells inhibited migration and invasion. These novel findings suggest that coordinated down-regulation of three miRNA clusters upon loss of p21 in unstressed cells promotes EMT, migration and invasion.
Citation Format: Xiao L. Li, Toshifumi Hara, Youngeun Choi, Murugan Subramanian, Princy Francis, Sven Bilke, Robert L. Walker, Marbin Pineda, Yu-an Yang, Ji Luo, Lalage M. Wakefield, Ben H. Park, Thomas Brabletz, Dipanjan Chowdhury, Paul S. Meltzer, Ashish Lal. A novel function of p21 in inhibition of epithelial-mesenchymal transition through microRNAs. [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 5331. doi:10.1158/1538-7445.AM2013-5331
Abstract 5337: MicroRNA-30c targets cytoskeleton genes involved in breast cancer cell invasion.
Authors: Bockhorn Jessica , Yee Kathy , Chang Ya-Fang , Prat Aleix , Huo Dezheng , Nwachukwu Chika , Dalton Rachel , Huang Simo , Swanson Kaitlin E. , Perou Charles M. , Olufunmilayo Olufunmilayo I. , Clarke Michael F. , Liu Huiping , Greene Geoffrey 
Published: August 2014

Abstract
Metastasis remains a significant challenge in treating cancer. MicroRNAs have emerged as important epigenetic regulators of various cellular processes during cancer development and progression. The goal of this study was to characterize signaling pathways for miRNA biomarkers that regulate breast cancer metastasis. Here we show that human breast tumor biomarker miR-30c regulates invasion by targeting the cytoskeleton network genes encoding Twinfilin 1 (TWF1) and Vimentin (VIM). Both VIM and TWF1 have been shown to regulate epithelial-to-mesenchymal transition (EMT). Similar to TWF1, VIM also regulates F-actin formation, a key component of cellular transition to a more invasive mesenchymal phenotype. To further characterize the role of the TWF1 pathway in breast cancer, we found that IL-11 is an important target of TWF1 that regulates breast cancer cell invasion and STAT3 phosphorylation. This miR-30c VIM/TWF1-IL11-pSTAT3 pathway will expedite the development of targeting strategies to prevent and treat breast tumor progression.
Citation Format: Jessica Bockhorn, Kathy Yee, Ya-Fang Chang, Aleix Prat, Dezheng Huo, Chika Nwachukwu, Rachel Dalton, Simo Huang, Kaitlin E. Swanson, Charles M. Perou, Olufunmilayo I. Olufunmilayo, Michael F. Clarke, Huiping Liu, Geoffrey Greene. MicroRNA-30c targets cytoskeleton genes involved in breast cancer cell invasion. [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 5337. doi:10.1158/1538-7445.AM2013-5337
Abstract 5342: Role of microRNAs in the development of prostate cancer.
Authors: Kumar Parameet , Dobi Albert , Petrovics George , Mohamed Ahmed , Srivastava Shiv , Biswas Roopa 
Published: August 2014

Abstract
Prostate Cancer (CaP) is the most common non-cutaneous form of cancer in men. It is also the second leading cause of cancer mortality in men in the USA. Oncogenic activation of the ETS Related Gene (ERG) as a result of gene fusions is the most common genomic alteration in prostate cancer reported to date. ERG has a milieu of transcriptional targets that regulate genes involved in various cellular processes including oncogenesis, inflammation, cell invasion, and DNA damage. Moreover, knockdown (KD) of ERG in TMPRSS2-ERG expressing CaP cells (VCaP) suppresses the growth and invasiveness of VCaP cells and in xenograft models. ERG protein has been implicated as a key player in the progression from pre-invasive to invasive disease status of CaP. Therefore, understanding mechanisms by which ERG promotes CaP progression is essential for developing novel prognostic/therapeutic targets for CaP. Our analyses of miRNA expressions in the human TMPRSS2-ERG fusion harboring VCaP cells compared to ERG-suppressed (with siRNA against ERG) VCaP controls indicate altered expression of miRNAs. Interestingly, we find that ERG suppresses the expression of miR-449a, which has been shown to regulate proliferation of CaP cells. In silico analyses (IPA and Genomatix) of cellular pathways targeted by these miRs focus on regulatory networks that are indicative of EMT and include molecules like DES (desmin), PDGFRA (platelet-derived growth factor receptor, alpha polypeptide) and TGFBR1 (transforming growth factor beta receptor 1). These pathways are potential candidate therapeutic targets. These data form the basis of new insights into the miRNA alterations in the context of major oncogenic activation in prostate cancer. Moreover, these miRNAs will provide novel prognostic marker and therapeutic targets for prostate cancer and will ultimately define CaP associated miRNAs in the context of ERG positive and ERG negative prostate cancers.
Supported by: United States Military Cancer Institute [RB] and [SS].
Citation Format: Parameet Kumar, Albert Dobi, George Petrovics, Ahmed Mohamed, Shiv Srivastava, Roopa Biswas. Role of microRNAs in the development of 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 5342. doi:10.1158/1538-7445.AM2013-5342
Abstract 5345: MicroRNA mediated regulation of a novel gene, MIEN1, in cancer metastasis.
Authors: Rajendiran Smrithi , Vishwanatha Jamboor K. 
Published: August 2014

Abstract
Migration and invasion enhancer gene 1(MIEN1), previously known as C17orf37, C35, ORB3, XTP4, RDX12, and MGC14832, is located in the 17q12 region of the human chromosome. MIEN1 expression is minimal to negligible in normal cells and tissues compared to its abundant expression in various cancers, including breast, prostate, oral and gastrointestinal carcinomas. MIEN1 works as a signaling molecule through the AKT/NF-κB pathway by up-regulating key proteases, matrix metalloproteinase - 9, urokinase - type plasminogen activator and vascular endothelial growth factor. We have shown that MIEN1 plays an important role in the migration and invasion of cancer through increased filopodia formation, hence promoting metastasis. The overall objective of this study is to identify the mechanisms that lead to the differential regulation of MIEN1 between normal and cancer cells. Our hypothesis is that MIEN1 is post-transcriptionally regulated by specific microRNA(s) that is (are) down-regulated in cancer, thus explaining its aberrant increased expression in cancer. MicroRNA expression profiling pattern predict several microRNAs that can directly bind to 3′UTR of MIEN1 mRNA. In silico analysis followed by northern blotting and real time PCR indicate a novel microRNA that regulates MIEN1 expression. This was further confirmed by decrease or increase in RNA and protein levels of MIEN1 as well as its downstream signaling effectors, upon microRNA mimic or inhibitor addition, respectively. Direct binding of the microRNA with MIEN1 mRNA was further confirmed by luciferase reporter assays, while the scratch wound healing and tumor invasion assays showed the functional significance of this microRNA on migration and invasion. Since the importance of MIEN1 as a key signaling molecule in cancer is well established, understanding the mechanism(s) involved in the regulation of MIEN1 will aid in designing novel and effective therapeutic strategies to treat cancer patients.
Citation Format: Smrithi Rajendiran, Jamboor K. Vishwanatha. MicroRNA mediated regulation of a novel gene, MIEN1, in cancer metastasis. [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 5345. doi:10.1158/1538-7445.AM2013-5345