bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3059: miR-518c-5p promotes the metastasis of oral cancer cells in a CXCR4-dependent and -independent manner
Authors: Kinouchi Makoto , Uchida Daisuke , Kuribayashi Nobuyuki , Tamatani Tetsuya , Nagai Hirokazu , Kawamata Hitoshi , Miyamoto Youji 
Published: August 2015

Abstract
We have demonstrated that CXCR4 system is involved in the metastatic process of oral cancer. Recently, we identified the miR-518c-5p as a downstream target of the CXCR4 system, which was involved in the metastasis of B88, a CXCR4-expressing oral cancer cell line (2014 AACR annual meeting). In this study, we examined the function of miR-518c-5p in an oral cancer cell line, CAL27, which did not express CXCR4 and did not exhibit metastatic potential in vivo. We transfected a miR-518c expression vector into parental CAL27 cells and isolated a stable transfectant, CAL27-518c. We could detect the upregulation of miR-518c-5p in the miR-518c transfectants compared with mock cells, which was completely inhibited by treatment with the miR-518c-5p LNA inhibitor. The growth and migration of CAL27-518c cells were significantly enhanced compared with those of mock cells. The miR-518c-5p inhibitor significantly impaired the enhanced cell growth and migration of CAL27-518c cells, indicating that these phenomena were mainly dependent on the expression of miR-518c-5p. Next, we examined the function of miR-518c-5p in vivo. miR-518c or mock transfectants were inoculated into the masseter muscle or the blood vessels of nude mice. Tumor volume, lymph nodes metastasis, and lung metastasis were significantly increased in the mice inoculated with miR-518c transfectants. These results indicate miR-518c-5p promotes the metastasis of oral cancer in a CXCR4-dependent and -independent manner.
Citation Format: Makoto Kinouchi, Daisuke Uchida, Nobuyuki Kuribayashi, Tetsuya Tamatani, Hirokazu Nagai, Hitoshi Kawamata, Youji Miyamoto. miR-518c-5p promotes the metastasis of oral cancer cells in a CXCR4-dependent and -independent manner. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3059. doi:10.1158/1538-7445.AM2015-3059
Abstract 3061: In vivo role of miR-32 in prostate cancer
Authors: Latonen Leena , Scaravilli Mauro , Zhang Fuping , Ruusuvuori Pekka , Poutanen Matti , Visakorpi Tapio 
Published: August 2015

Abstract
The androgen receptor (AR) signaling pathway is central to the emergence of castration-resistant prostate cancer (CRPC). We set out to identify androgen-regulated microRNAs (miRNAs) that may contribute to the development of CRPC. We found miR-32 to be an androgen regulated miRNA which is differentially expressed in CRPC compared to benign prostatic hyperplasia (BPH) and able to provide a significant growth advantage to LNCaP cells by reducing apoptosis
To study how increased miR-32 expression contributes to prostate cancer formation and/or progression in vivo, and to search for in vivo targets of miR-32 in the prostate tissue, we have established transgenic mice expressing miR-32 specifically in the prostate. FVB/N mouse strain was used to create transgenic mice with probasin promoter (ARR2PB) driving expression of miR-32 androgen-responsively in prostate epithelium post-puberty. The mice develop and breed normally, and express the transgene specifically in the ventral and dorsolateral lobes of the prostate, with no transgene expression detected in anterior prostate or seminal vesicles up to six months of age. To provoke lesions in prostate epithelium, the miR-32 mice were cross-bred with mice heterozygous for tumor suppressor Pten. Histological analysis of the prostates of ARR2PB-miR-32xPten+/- mice shows increased number of prostatic intraepithelial neoplasia (PIN) lesions in the dorsal prostate compared to Pten+/- mice. In addition, transgenic miR-32 can induce goblet cell metaplasia in prostate epithelium in lateral to ventral prostate, in addition to stromal responses, in the prostate in the Pten+/- background.
In search for in vivo targets of miR-32, we have performed a gene expression microarray analysis comparing the wild type and ARR2PB-miR-32 prostate tissue. Several candidate targets have been identified, and will be discussed further for their potential cancer relevance.
We find that miR-32 is potentially an important gene in the progression of prostate cancer and a putative drug target. We are currently analyzing histology of the miR-32 transgenic mouse prostates further, and assessing tissue targets of miR-32. With the transgenic mouse model, we aim to determine whether miR-32 is an oncomiR for prostate cancer in vivo, and will assess the potency of miR-32 as a therapeutic target.
Citation Format: Leena Latonen, Mauro Scaravilli, Fuping Zhang, Pekka Ruusuvuori, Matti Poutanen, Tapio Visakorpi. In vivo role of miR-32 in prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3061. doi:10.1158/1538-7445.AM2015-3061
Abstract 3062: miR-671-5p promotes epithelial-to-mesenchymal transition by downregulating FOXM1 expression in breast cancer
Authors: Tan Xiaohui , Fu Yebo , Chen Liang , An Shejuan , Lee Woojin , Lai Yinglei , Rezaei Katayoon , Tabbara Sana , Teal Christine B. , Man Yan-gao , Siegel Robert , Brem Rachel F. , Fu Sidney W. 
Published: August 2015

Abstract
microRNA (miRNA) dysfunction is associated with a variety of human diseases including cancer. Our previous study showed that miR-671-5p was deregulated during breast cancer progression. We aim to decipher the functional mechanism of miR-671-5p in breast cancer. We found that expression of miR-671-5p was decreased significantly in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) compared to normal and atypical ductal hyperplasia (ADH) in the microdissected formalin-fixed, paraffin-embedded (FFPE) tissues. Forkhead Box M1 (FOXM1), as an oncogenic transcription factor, was predicted as one of the direct targets of miR-671-5p, which was subsequently confirmed by luciferase assays. Forced expression of miR-671-5p in breast cancer cell lines downregulated FOXM1 expression, and attenuated the proliferation and invasion in breast cancer cell lines. Notably, overexpression of miR-671-5p resulted in a shift from epithelial-to-mesenchymal transition (EMT) to mesenchymal-to-epithelial transition (MET) phenotypes in MDA-MB-231 breast cancer cells and induced S-phase arrest. Moreover, miR-671-5p sensitized breast cancer cells to cisplatin, 5-fluorouracil (5-FU) and epirubicin exposure. Host cell reactivation (HCR) assays showed that miR-671-5p reduces DNA repair capability in post-drug exposed breast cancer cells. These data indicates that miR-671-5p functions as a tumor suppressor miRNA by directly targeting FOXM1 in breast cancer. Hence, miR-671-5p may serve as a novel therapeutic target for breast cancer management.
Citation Format: Xiaohui Tan, Yebo Fu, Liang Chen, Shejuan An, Woojin Lee, Yinglei Lai, Katayoon Rezaei, Sana Tabbara, Christine B. Teal, Yan-gao Man, Robert Siegel, Rachel F. Brem, Sidney W. Fu. miR-671-5p promotes epithelial-to-mesenchymal transition by downregulating FOXM1 expression in breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3062. doi:10.1158/1538-7445.AM2015-3062
Abstract 3070: MicroRNA-155 directly targets PDCD4 and activates BIC promoter through AP-1 dependent transcription to replenish miR-155 expression in SAS cells
Authors: zargar shabir A. , Karunagaran Devarajan 
Published: August 2015

Abstract
Pdcd4 (programmed cell death 4) has been demonstrated to be a tumor suppressor gene and is expressed at higher levels during apoptosis. PDCD4 is down regulated in a subset of oral cancers (tongue and buccal cavity) and an association between its down-regulation by miR-21 and tumorigenesis and invasion in oral carcinoma has been demonstrated. In this study we show that miR-155 directly targets PDCD4 in SAS (tongue squamous carcinoma) cells. We demonstrate a positive feedback loop between miR-155 expression and AP-1 dependent transcription through the down regulation of PDCD4. Analysis of miR-155 promoter (BIC) showed the presence of NF-κB and AP-1 (c-Jun and c-Fos) transcription factor binding sites and PDCD4 is known to inhibit AP-1 dependent transcription. Ectopic expression of PDCD4 in SAS cells drastically reduced the BIC promoter activity via inhibition of AP-1 dependent transcription and down regulated the levels of miR-155. We also generated the Lentiviral based miR-155 sponge stable cells to down regulate miR-155 in SAS cells, and found an increase in PDCD4 protein levels. The activity of BIC promoter was relatively low in miR-155 sponge stable cells compared to control sponge stable cells as analyzed by a dual luciferase reporter assay. We have also seen the reduced rate of proliferation in miR-155 sponge stable cells compared to control sponge stable cells. Thus our data show that miR-155 directly targets PDCD4 and consequently activates AP-1 dependent transcription in BIC promoter and increasing the levels of miR-155.
Citation Format: shabir A. zargar, Devarajan Karunagaran. MicroRNA-155 directly targets PDCD4 and activates BIC promoter through AP-1 dependent transcription to replenish miR-155 expression in SAS cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3070. doi:10.1158/1538-7445.AM2015-3070
Abstract 3071: MicroRNA-486 (miR-486) promotes invasion by targeting RECK in nasopharyngeal carcinoma cells
Authors: Lin Chin-Tarng , Wu Cheng-Der 
Published: August 2015

Abstract
Nasopharyngeal carcinoma (NPC) is a common cancer in Taiwanese and people living in the southeastern region of China. In order to investigate NPC pathogenesis, our laboratory has previously established NPC-TW01 cell line, which was derived from a Taiwanese NPC patient. We also established a NPC-TW01N1 cell line, which was derived from the NPC xenograft in SCID mouse. Both NPC-TW01 and NPC-TW01N1 cell lines have an identical DNA profile (STR). NPC-TW01N1 cell line has higher malignant potency than NPC-TW01 line. For example, the proliferation and invasion capabilities of NPC-TW01N1 line were higher than that of NPC-TW01 line. When we used microRNA microarray to compare the endogenous microRNA expression profiles between NPC-TW01 and NPC-TW01N1 lines, the miR-486, miR-200a and other miRNAs showed higher expression in NPC-TW01N1 cell. Transfection of exogenous miR-486 or anti-miR-486 into NPC-TW01 cells or NPC-TW01N1 cells revealed that miR-486 involves in the regulation of NPC cell progression and invasion. To determine whether miR-486 targeted gene involves in progression and invasion, we analyzed microRNA targeted gene database, Ingenuity pathway databases, and cDNA expression microarrays from miR-486 transfected cells. We found that the RECK gene is one of miR-486 candidate targeted genes that involves in NPC cell progression and invasion. We used pmirGLO luciferase reporter vector assays to demonstrate that miR-486 directly targets RECK 3′ UTR. When we transfected miR-486 or RECK siRNA into NPC cells, we found that they can accelerate tumor progression and invasion. It is concluded that miR-486 and RECK genes maybe potential targets for NPC therapy.
Citation Format: Chin-Tarng Lin, Cheng-Der Wu. MicroRNA-486 (miR-486) promotes invasion by targeting RECK in nasopharyngeal carcinoma cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3071. doi:10.1158/1538-7445.AM2015-3071
Abstract 3073: Reorganization of metastamiRs in the evolution of metastatic aggressive high-risk neuroblastoma
Authors: Khan Faizan Haider , Ramraj SatishKumar , Aravindan Sheeja , Natarajan Mohan , Herman Terence H. , Aravindan Natarajan 
Published: August 2015

Abstract
MetastamiRs have momentous clinical relevance and have been correlated with disease progression in many tumors. In this study, we identified neuroblastoma metastamiRs exploiting unique mouse models of favorable and high-risk metastatic human neuroblastoma. Further, we related their deregulation to the modulation of target proteins and established their association with clinical outcomes. Whole genome miRNA microarray analysis identified 74 metastamiRs across the manifold of metastatic tumors. RT-qPCR on select miRNAs validated profile expression. Results from bio-informatics across the ingenuity pathway, miRCancer, and literature data-mining endorsed the expression of these miRNAs in multiple tumor systems and showed their role in metastasis, identifying them as metastamiRs. Immunoblotting and TMA-IHC analyses revealed alterations in the expression/phosphorylation of metastamiRs’ targets, including ADAMTS-1, AKT1/2/3, ASK1, AURKβ, Birc1, Birc2, Bric5, β-CATENIN, CASP8, CD54, CDK4, CREB, CTGF, CXCR4, CYCLIN-D1, EGFR, ELK1, ESR1, CFOS, FOSB, FRA, GRB10, GSK3β, IL1α, JUND, kRAS, KRTAP1, MCP1, MEGF10, MMP2, MMP3, MMP9, MMP10, MTA2, MYB, cMYC, NF2, NOS3, P21, pP38, PTPN3, CLEAVED PARP, PKC, SDF-1β, SEMA3D, SELE, STAT3, TLR3, TNFα, TNFR1, and VEGF in aggressive cells ex vivo and in a manifold of metastatic tumors in vivo. Clinical outcome association analysis with the validated metastamiRs’ targets correlated strongly with poor overall and relapse-free survival. For the first time, these results identified a comprehensive list of neuroblastoma metastamiRs, related their deregulation to altered expression of protein targets, and established their association with poor clinical outcomes. The identified set of distinctive neuroblastoma metastamiRs could serve as potential candidates for diagnostic markers for the switch from favorable to high-risk metastatic disease.
Citation Format: Faizan Haider Khan, SatishKumar Ramraj, Sheeja Aravindan, Mohan Natarajan, Terence H. Herman, Natarajan Aravindan. Reorganization of metastamiRs in the evolution of metastatic aggressive high-risk neuroblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3073. doi:10.1158/1538-7445.AM2015-3073
Abstract 3079: Mechanism of hsa-miR-15a in EMT and chemoresistance in colorectal cancer
Authors: Fesler Andrew , Zhai Haiyan , Ju Jingfang 
Published: August 2015

Abstract
Epigenetic alterations such as non-coding microRNAs are critical factors in EMT and chemoresistance. Hsa-miR-15a, as one of the first miRNA identified to be associated with cancer, has been investigated for its role in several types of cancer. We are interested in understanding the molecular and cellular mechanism of hsa-miR-15a in colorectal cancer as hsa-miR-15a is down-regulated in colon cancer and associated with poor patient prognosis. In this study, we have identified several direct key targets of hsa-miR-15a that impact EMT transition, cell cycle and apoptosis. Our results show that the expression of BMI-1, an important regulator of EMT, was suppressed by hsa-miR-15a. The reduction of hsa-miR-15a in colorectal cancer patient samples was significantly inversely correlated with BMI-1 over-expression. Hsa-miR-15a also suppresses the expression of anti-apoptotic protein BCL-2. The suppression of BMI-1, BCL-2 as well as other key targets by hsa-miR-15a has potential for increasing chemosensitivity as well as disrupting cancer stem cell self renewal. In addition, hsa-miR-15a also has potential as a prognostic biomarker in colorectal cancer. This work will provide a further understanding of the mechanism of hsa-miR-15a loss in colorectal cancer and its clinical significance in relationship with its targets and pathways. The functional significance of hsa-miR-15a in regulating key targets and pathways establishes the foundation for hsa-miR-15a as a potential novel therapeutic strategy for treating colorectal cancer.
Citation Format: Andrew Fesler, Haiyan Zhai, Jingfang Ju. Mechanism of hsa-miR-15a in EMT and chemoresistance in colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3079. doi:10.1158/1538-7445.AM2015-3079
Abstract 308: The role of PTEN PDZ-binding domain in mammary gland tumorigenesis
Authors: Yan Mingfei , Or Penelope , Chan Andrew 
Published: August 2015

Abstract
PTEN functions as a key negative regulator of PI3K-Akt pathway through its lipid phosphatase activity. Mutations or loss of PTEN is frequently observed in brain, breast, prostate and endometrial cancer. PTEN also possesses a PDZ-binding domain (PDZ-BD) at its carboxyl terminus, which can be recruited by PDZ-containing proteins like ZO-1 to cell tight junction. Therefore, PTEN may have a potential role in regulating epithelial tight junction integrity. To study the role of PTEN PDZ-BD in breast epithelial tumorigenesis, a PTEN-ΔPDZ mice lacking this domain was generated and further crossed with MMTV-PyMT breast cancer model. As a result, PTENΔPDZ/MMTV-PyMT mice show enhanced tumor growth and metastasis. To elucidate tumor suppressive mechanisms of PTEN PDZ-BD, three-dimensional cultures of PTENΔPDZ mouse mammary epithelial cells (MMEs) was carried out. Though PTEN-ΔPDZ MMEs spheres have normal morphogenesis in 3D culture, they possess larger diameters than wild-type (WT). Besides, both tight junction (ZO-1) and adherent junction (E-Cadherin) of MMEs were examined in 3D culture, though no major differences in cell junction and polarity was observed between PTEN-ΔPDZ and PTEN-WT. Future work will study signaling activities of PTEN-ΔPDZ/MMTV-PyMT breast cancer cells, morphogenesis, polarity and cell junction of PTEN-ΔPDZ/MMTV-PyMT MMEs in 3D cultures.
This work was supported by NIH RO1 (CA133669), Hong Kong Research Grant Council (460713) and Hong Kong PhD Fellowship Scheme (PF12-13584)
Citation Format: Mingfei Yan, Penelope Or, Andrew Chan. The role of PTEN PDZ-binding domain in mammary gland tumorigenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 308. doi:10.1158/1538-7445.AM2015-308
Abstract 3094: Sprouty and cell proliferation in colorectal cancer
Authors: Zhang Qiong , Shim Katherine , Wright Kevin , Jurkevich Alexander , Khare Sharad 
Published: August 2015

Abstract
BACKGROUND & AIMS: Sprouty (SPRY) proteins are evolutionarily conserved modulators of mitogen-activated protein kinase pathway. SPRY2 appears to function as a tumor suppressor in other cancers, whereas we reported that SPRY2 functions as an oncogene in colorectal cancer (CRC). To further understand the oncogenic potential of SPRY1 and SPRY2 in CRC, we investigated the mechanisms by which these proteins regulate cell proliferation in CRC. MATERIALS & METHODS: Human CRC cDNA arrays were employed to assess mRNA levels of SPRY1, SPRY2 and p21. SPRY1 and SPRY2 were knocked-down in CaCo2 colon cancer cells by siRNA. Effects of SPRY were assessed by immunoblotting, real time PCR, luciferase reporter assay, and confocal microscopy. Mouse embryonic fibroblasts (MEFs) derived from SPRY mutant mice were utilized to dissect SPRY functions in mesenchymal cells. RESULTS: In this study, surprisingly, we present evidence to suggest that concomitant activation of ERK, p-38 and AKT signaling cascades is insufficient to drive cancer cell proliferation in SPRY modulated cells. Suppression of SPRY in colon cancer cells upregulates p21, a cell cycle inhibitor. SPRY2 dependent p21 promoter activation may account for upregulation of p21 expression and inhibition of cancer cell proliferation. Underscoring the biological relevance of these findings, recombination of floxed SPRY1 and SPRY2 alleles in mouse embryonic fibroblasts (MEFs) resulted in increased expression of p21. Finally, in a human CRC cDNA array we established an inverse correlation of SPRY1 and SPRY2 with p21 mRNA expression. CONCLUSIONS: Together, this study indicates that SPRY is a target of therapeutic intervention in CRC.
Citation Format: Qiong Zhang, Katherine Shim, Kevin Wright, Alexander Jurkevich, Sharad Khare. Sprouty and cell proliferation in colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3094. doi:10.1158/1538-7445.AM2015-3094
Abstract 3102: AZD1152HQPA Accurin™ nanoparticles inhibit growth of diffuse large B-cell lymphomas and small cell lung cancer
Authors: Ashton Susan , Taylor Paula , Curtis Nicola , Pilling James , Dorval Thierry , Hrkach Jeff , Jewsbury Philip J. , Barry Simon T. 
Published: August 2015

Abstract
Inhibitors of the Aurora Kinases have been developed to treat both liquid and solid tumours. The prodrug AZD1152 is an inhibitor of Aurora kinase B that is clinically active in acute myeloid leukaemia. Despite this clinical proof-of-concept, the broader clinical utility of AZD1152 is limited by the requirement for continuous IV infusion, and the mechanism-related dose-limiting toxicities seen with this class of inhibitors, in particular bone marrow toxicity. To address these challenges and maximise the clinical utility, an Accurin nanoparticle containing AZD1152HQPA, the active metabolite of AZD1152, has been developed. In preclinical models, the AZD1152HQPA Accurin shows increased efficacy without the bone marrow toxicity seen with the prodrug formulation. In preclinical studies, models of Diffuse Large B Cell Lymphoma (DLBCL) and Small Cell Lung Cancer (SCLC) show sensitivity to monotherapy Aurora B kinase inhibitors. Consistent with this, AZD1152 inhibits the growth of subsets of DLBCL and SCLC cells lines in vitro, while in vivo, AZD1152HQPA Accurin consistently reduces the growth of DLBCL and SCLC models. When given at 25mg/kg on days 1 and 3, AZD1152HQPA Accurin gave either equivalent or superior activity to AZD1152 delivered at 25mg/kg on days 1, 2, 3 and 4. When the dose-schedule was explored, increasing the dose intensity increases the anti-tumour effect, while modifying the timing and dose intensity of each dose cycle also influenced the anti-tumour activity. In a DLBCL model, low dose AZD1152HQPA Accurin (25mg/kg delivered as a fractionated dose on day 1 and 3) gave tumour stasis or partial regression, while a higher dose (50mg/kg delivered weekly) gave increased tumour response, which was durable on repeated dosing. The timing of AZD1152HQPA Accurin doses had significant impact on the shape of the tumour response, indicating that optimal scheduling is important to maximize the benefits of sustained release and enhanced tumour accumulation of Accurin nanoparticles. Collectively the preclinical data indicate that the AZD1152HQPA Accurin has the potential for activity in SCLC and DLBCL; is able to be used flexibly; and has an improved therapeutic index.
Citation Format: Susan Ashton, Paula Taylor, Nicola Curtis, James Pilling, Thierry Dorval, Jeff Hrkach, Philip J. Jewsbury, Simon T. Barry. AZD1152HQPA Accurin™ nanoparticles inhibit growth of diffuse large B-cell lymphomas and small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3102. doi:10.1158/1538-7445.AM2015-3102