bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4353: microRNA-196b induces epithelial-to-mesenchymal transition through targeting HOXA9 in non-small cell lung cancer cells
Authors: Son Ji Woong , Yu Seong-Lan , Lee Dong Chul , Lee Shin Yup , Park Chang Gyo , Lee Hoi Young , Kang Jaeku 
Published: May 2015

Abstract
MicroRNAs (miRNAs) play important roles as oncogenes or tumor suppressor through modulation of expression of target genes as posttranscriptional regulators. miR-196b has been previously reported dysregulation in multiple tumor types including gastric cancer, colorectal cancer, glioblastoma and breast cancer. However, there is unknown about the role of miR-196b in lung cancer. There has been reported reduction of invasiveness via Homeobox A9 (HOXA9) overexpression in non-small cell lung cancer (NSCLC) cells. We identified an inverse expression between miR-196b and HOXA9 in clinical samples compared to their corresponding normal counterparts. We demonstrated that HOXA9 expression was significantly regulated through alteration of miR-196b expression and miR-196b overexpression or knockdown of HOXA9 induced invasion in NSCLC cells. Moreover, the expression levels of matrix metalloproteinase (MMP) 9 and plasminogen activator, urokinase (uPA) associated with epithelial-mesenchymal transition (EMT) was induced by miR-196b overexpression or knockdown of HOXA9. In addition, the expression level of N-cadherin (Cdh2) was increased by upregulation of miR-196b and knockdown of HOXA9 decreased E-cadherin (Cdh1) expression. Therefore, our findings suggest that miR-196b may be potential therapeutic target in lung cancer.
Citation Format: Ji Woong Son, Seong-Lan Yu, Dong Chul Lee, Shin Yup Lee, Chang Gyo Park, Hoi Young Lee, Jaeku Kang. microRNA-196b induces epithelial-to-mesenchymal transition through targeting HOXA9 in non-small cell lung 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 4353. doi:10.1158/1538-7445.AM2014-4353
Abstract 4358: MicroRNA-198 inhibits non-small cell lung cancer migration and invasion through targeting OTX1 and VCP
Authors: Kim Jin-Ah , Yang Junguk , Jo Yeong Nang , Lee Chang Woo , Lee Ok-Jun , Choi Song-Yi , Kang Jong Soon , Yun Jieun 
Published: May 2015

Abstract
Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. In previous studies, microRNA-198 (miR-198) was shown to be significantly downregulated in lung adenocarcinoma-associated malignant pleural effusion and suggested as a diagnostic biomarker. Herein, we show that miR-198 regulates migration and invasion of NSCLS cells by directly targeting orthodenticle homeobox 1 (OTX1) and valosin containing protein (VCP). Expression of miR-198 suppressed migration and invasion of NSCLS cells, whereas inhibition of miR-198 expression increased the invasive efficiency of the cancer cells. MiR-198 directly targets 3′UTR of OTX1 and VCP, thus regulates their protein level. Furthermore, we found reduced levels of miR-198 in human NSCLS tissue samples compared to adjacent normal tissues. Our findings indicate that miR-198 regulates NSCLC cell migration and invasion, partially via the down-regulation of OTX1 and VCP. Thus, miR-198 may represent a potential therapeutic target for NSCLC intervention.
Citation Format: Jin-Ah Kim, Junguk Yang, Yeong Nang Jo, Chang Woo Lee, Ok-Jun Lee, Song-Yi Choi, Jong Soon Kang, Jieun Yun. MicroRNA-198 inhibits non-small cell lung cancer migration and invasion through targeting OTX1 and VCP. [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 4358. doi:10.1158/1538-7445.AM2014-4358
Abstract 4367: Tumor suppressor miR-30a inhibits LOX expression and progression in anaplastic thyroid cancer
Authors: Boufraqech Myriem , Nilubol Naris , Zhang Lisa , Sadowski Samira , Gara Sudheer Kumar , He Mei , Davis Sean , Quezado Martha , Kebebew Electron 
Published: May 2015

Abstract
one of the most aggressive human malignancies with a median survival time of less than one year. A better understanding of the molecular events involved in ATC initiation and progression that could be targeted for therapy is gravely needed. There is limited data on the role of miRNAs in ATC. Screening of miRNA expression profile in thyroid cancer samples showed significant downregulation of miR-30a in ATC compared to differentiated thyroid cancer and normal tissue. Ectopic expression of miR-30a in vitro decreased invasion and migration of ATC cells with downregulation of epithelial-mesenchymal transition (EMT) markers and Lysyl Oxidase (LOX) expression, a predicted target of miR-30a. Using an in vivo mouse model of ATC metastases, miR-30a significantly decreased lung metastasis with decreased vimentin, CD44 and LOX expression in lung metastases tumor tissue. We also found that LOX and its downstream target TWIST-1 are highly expressed in ATC, and the expression of both were significantly, inversely correlated with miR-30a expression (p= 0.0026). In addition, the analysis of 454 primary thyroid cancer samples from The Cancer Genome Atlas dataset demonstrated upregulation of LOX and downregulation of miR-30a in high-risk thyroid cancer. These findings suggest that LOX and miR-30a are prognostic markers for aggressive thyroid cancer.
To determine whether LOX is a direct effector of miR-30a, the 3′UTR region of LOX was cloned into a luciferase reporter plasmid. Transient transfection of 3′UTR-LOX along with miR-30a in ATC cell lines led to a decrease in luciferase activity when compared to the co-transfection of 3′UTR-LOX with negative control miRNA, demonstrating that LOX is a direct target of miR-30a.
In vitro treatment of 4 ATC cell lines with β-aminoproprionitrile (BAPN), an irreversible inhibitor of LOX, had no effect on cell proliferation but inhibited cell invasion and migration and significantly decreased EMT markers and CD44 expression. Moreover, BAPN-treated mice with metastatic human ATC tumors had significantly fewer tumors and smaller size of lung metastases. Our data taken together support a critical role of miR-30a in ATC progression, which is mediated by LOX, and suggests that miR-30a and LOX is possible therapeutic target in ATC.
Note: This abstract was not presented at the meeting.
Citation Format: Myriem Boufraqech, Naris Nilubol, Lisa Zhang, Samira Sadowski, Sudheer Kumar Gara, Mei He, Sean Davis, Martha Quezado, Electron Kebebew. Tumor suppressor miR-30a inhibits LOX expression and progression in anaplastic thyroid 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 4367. doi:10.1158/1538-7445.AM2014-4367
Abstract 4369: The microRNA-218-survivin axis regulates cervical cancer cell migration and invasion
Authors: Kogo Ryunosuke , How Christine , Bruce Jeff , Shi Willa , Yip Kenneth W. , Ailles Laurie , Liu Fei-Fei 
Published: May 2015

Abstract
MicroRNA (miR)-218 down-regulation has been reported in numerous human malignancies. In cervical cancer, we identified that lower miR-218 expression was significantly associated with poorer overall survival, disease-free survival, and pelvic/para-aortic lymph node recurrence. Further analyses of cervical cancer data from The Cancer Genome Atlas (TCGA) identified that this down-regulation was associated with a genomic locus loss (hsa-mir-218-1:4p15.31, hsa-mir-218-2:5q34, n=105). The objective of the current study was to elucidate the cellular and molecular functions of miR-218. MiR-218 transfection into cervical cancer cells (SiHa and ME-180) significantly reduced cell migration (by 66% and 89%, respectively), invasion (by 49% and 67%, respectively), and clonogenic capacity (by 42% and 53%, respectively), relative to control-transfected cells (P&lt;0.05). In order to identify clinically relevant miR-218 target genes, we used an integrated trimodal approach, incorporating DNA microarray (Affymetrix Human Genome U133 Plus 2.0) analyses of 79 clinical samples, miR-218 transfection, and miRDB target prediction. The most significant target was survivin (BIRC5); miR-218 transfection confirmed a reduction in survivin mRNA and protein expression in both SiHa and ME-180 cells. Furthermore, a direct interaction between the survivin-3′UTR and miR-218 was validated using a luciferase reporter assay. siRNA knockdown of survivin in SiHa and ME-180 significantly reduced cell migration (by 76% and 83%, respectively), invasion (by 79% and 88%, respectively), and clonogenic capacity (by 98% and 97%, respectively), relative to control cells (P&lt;0.05). YM155, a small-molecule survivin suppressant, effectively reduced survivin mRNA and protein levels in a concentration- and time-dependent manner. This compound correspondingly decreased cervical cancer cell proliferation and clonogenic survival. Our results suggest that the miR-218-survivin axis plays an important role in cervical cancer progression.
Citation Format: Ryunosuke Kogo, Christine How, Jeff Bruce, Willa Shi, Kenneth W. Yip, Laurie Ailles, Fei-Fei Liu. The microRNA-218-survivin axis regulates cervical cancer cell migration and invasion. [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 4369. doi:10.1158/1538-7445.AM2014-4369
Abstract 4376: Upregulation of miR-21 in cisplatin-resistant ovarian cancer via JNK-1/c-Jun pathway
Authors: Echevarria Ileabett M. , Encarnacion Joel , Valiyeva Fatma , Vivas Pablo 
Published: May 2015

Abstract
Cisplatin has been the most accepted drug for the treatment of ovarian cancer for almost 40 years. Although the majority of patients with ovarian cancer respond to front-line platinum combination chemotherapy, many patients will develop cisplatin-resistance disease, which is extremely rapid and fatal. Although various mechanisms of cisplatin resistance have been postulated, the key molecules involved in such resistance have not been identified. MiRNAs are endogenously expressed small non-coding RNAs, which are evolutionarily conserved and function as post-transcriptional regulators of gene expression. Dysregulation of miRNAs have been associated with cancer initiation, progression and drug resistance. The oncogenic miRNA-21, one of the best-studied miRNAs, is upregulated in almost all human cancers. However, the regulation of miR-21 in cisplatin resistant ovarian cancer cells has not been assessed. In this study, we measured the miR-21 expression by real-time PCR and found upregulation of miR-21 in cisplatin resistant compared with cisplatin sensitive ovarian cancer cells. Chromatin immunoprecipitation studies demonstrated the association of the c-Jun transcription factor to the mir-21 DNA promoter regions. Blocking the JNK-1, the major activator of c-Jun phosphorylation, reduced the expression of miR-21 and increased the expression of its well-known target gene, PDCD4. Overexpression of miR-21 in cisplatin sensitive cells decreased PDCD4 levels and increased cell proliferation. Finally, targeting miR-21 reduced cell growth, proliferation and invasion of cisplatin resistant ovarian cancer cells. These results suggest that the JNK-1/c-Jun/miR-21 pathway contributes to the cisplatin resistance of ovarian cancer cells and demonstrated that miR-21 is a plausible target to overcome cisplatin resistance.
Citation Format: Ileabett M. Echevarria, Joel Encarnacion, Fatma Valiyeva, Pablo Vivas. Upregulation of miR-21 in cisplatin-resistant ovarian cancer via JNK-1/c-Jun pathway. [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 4376. doi:10.1158/1538-7445.AM2014-4376
Abstract 4378: miR-100 mediates resistance to paclitaxel in cervical cancer cells
Authors: Kato Rina , Nishi Hirotaka , Nagamitsu Yuzo , Sasaki Toru , Isaka Keiichi 
Published: May 2015

Abstract
Objectives: Hypoxia occurs during development of cervical cancer and is considered to correlate with its resistance to chemotherapy. We found that hypoxia induced miR-100 whose expression was low in cervical cancer. We sought to determine the regulators of the paclitaxel response during hypoxia in cervical cancer. Methods and Results: We found that the expression of miR-100 was significantly higher under hypoxic condition (1% O2) by realtime RT-PCR. According to the results of in silico analysis, miR-100 targeted human ubiquitin-specific protease (USP) 15. Hypoxia and overexpression of miR-100 respectively decreased the activity of luciferase-reporter containing the 3′-untranslated region (UTR) of USP15 with the predicted miR-100-binding site in cervical cancer cell lines, SiHa and HeLa. By western blot analysis, hypoxia enhanced the endogenous USP15 protein expression. USP15 mRNA level was also up-regulated by hypoxia using realtime RT-PCR. Overexpression of miR-100 induced paclitaxel resistance reducing apoptosis using MTT assays and annexin V staining. Conclusions: Our results provide evidence that regulation of USP15 expression by miR-100 represents a mechanism for paclitaxel resistance in cervical cancer. Our results suggest that miR-100 and USP15 could be a therapeutic target in paclitaxel-resistant cervical cancer.
Citation Format: Rina Kato, Hirotaka Nishi, Yuzo Nagamitsu, Toru Sasaki, Keiichi Isaka. miR-100 mediates resistance to paclitaxel in cervical 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 4378. doi:10.1158/1538-7445.AM2014-4378
Abstract 4406: Role of KRAS in modulating the metabolomic profile and the response of NSCLC cells to PI3K/mTOR and AMPK interfering agents
Authors: Caiola Elisa , Brunelli Laura , Marabese Mirko , Garassino Marina Chiara , Farina Gabriella , Broggini Massimo , Pastorelli Roberta 
Published: May 2015

Abstract
Background: Non-small-cell lung cancers (NSCLC) constitute the majority of lung cancer cases, whose risk is associated with environmental factors, such as air pollution, and smoking habits. KRAS mutations are present in about 20% of NSCLC patients, mostly at codon 12 and have been associated to tumor progression and resistance to chemotherapy in many types of cancer. Increasingly evidences seem to highlight that the definition of KRAS status is not sufficient to determine its predictive and/or prognostic role in NSCLC, and indicate that different KRAS mutations could differently impact on crucial cellular processes. An issue still to be addressed is whether different KRAS mutations may modulate cellular metabolism with possible implications on different response to anticancer treatments which specifically inhibit metabolism modulating pathways, such as the PI3K/AKT/mTOR axis.
Methods: We generated from the human NSCLC cell line NCI-H1299 clones overexpressing WT KRAS, and the three most common NSCLC KRAS mutations (G12C, G12V and G12D). The clones were used to determine in vitro response to PI3K, mTOR and AMPK interfering agents. We applied an explorative mass spectrometry-based untargeted metabolomics strategy to characterize the largest possible number of metabolites that might distinguish the different KRAS mutated clones.
Results: KRAS overexpressing clones resulted sensitive to the PI3K inhibitors BKM-120 and PIK-75 and to the PI3K/mTOR dual inhibitor BEZ-235. Metformin (acting on AMPK) did not display a cytotoxic activity on the clones at concentrations below or equal to 1mM. Metabolomics analyses revealed that clones harboring different KRAS mutations at codon 12 had different metabolic remodellings such as different redox buffering system and different glutamine-dependency.
Conclusion: The preliminary findings reported herein indicate that specific KRAS mutations at codon 12 are associated to different metabolomics profiles that might have an impact to the response to anticancer treatments. Combination studies including metformin and PI3K/mTOR interfering agents and more detailed metabolomics analyses are ongoing in order to clarify whether metabolic adaptations dependent on KRAS mutants might account for the behaviour of KRAS overexpressing clones treated with different drugs.
Citation Format: Elisa Caiola, Laura Brunelli, Mirko Marabese, Marina Chiara Garassino, Gabriella Farina, Massimo Broggini, Roberta Pastorelli. Role of KRAS in modulating the metabolomic profile and the response of NSCLC cells to PI3K/mTOR and AMPK interfering agents. [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 4406. doi:10.1158/1538-7445.AM2014-4406
Abstract 441: Functional characterization of recurrent CD74-NRG1 fusions in lung adenocarcinoma
Authors: Plenker Dennis , Fernandez-Cuesta Lynnette , Osada Hirotaka , Sun Ruping , Bos Marc , Daßler Juliane , Wright Gavin , Brambilla Elisabeth , Büttner Reinhard , Ansen Sascha , Haas Stefan , Yatabe Yasushi , Thomas Roman K. 
Published: May 2015

Abstract
In nearly 50% of all lung adenocarcinomas the oncogenic driver is still unknown. We performed transcriptome sequencing on 25 pan-negative lung adenocarcinomas of never smokers leading to the identification of the novel CD74-NRG1 gene fusion. In an additional cohort of 102 adenocarcinomas we could identify and validate four additional cases bearing the CD74-NRG1 fusion gene - all of the invasive mucinous subtype.
We then transduced NIH-3T3 cells with the fusion and found it localized on the cell surface in FACS experiments. As we found the identical breakpoint in CD74 in our fusion as in CD74-ROS1, we hypothesized that the functional active part needs to be NRG1. (Soda et al. 2012) The NRG1 isoform III-β3 that we found is generally not expressed in lung tissue - therefore the CD74 part leads to the expresseion of NRG1 III-β3 in the lung. As Neuregulins are known interaction partners of HER receptor family members we transduced the human adenocarcinoma cell lines H322 and H1568, that are HER receptor and KRAS wildtype, with the fusion and found phosphorylation of HER2 and HER3 in the transduced cells under starvation conditions compared to empty vector controls. (Hobbs et al. 2002) This holds true as well in the patient situation in which phospho-HER3 was only found in tumors expressing the fusion (p&lt;0.0001).
We could further show that the CD74-NRG1 fusion is associated with activation of the phosphoinsitide-3-kinase pathway activation and the mitogen-activated protein (MAP) kinase pathway . As functional consequence we could observe in several human adenocarcinoma cell lines increased colony forming ability in soft-agar assays showing the CD74-NRG1 fusion being a new oncogenic driver in lung adenocarcinoma. This finding may lead to new treatment options for patients harboring this fusion gene who do not benefit from any effective treatment option up to now.
Citation Format: Dennis Plenker, Lynnette Fernandez-Cuesta, Hirotaka Osada, Ruping Sun, Marc Bos, Juliane Daßler, Gavin Wright, Elisabeth Brambilla, Reinhard Büttner, Sascha Ansen, Stefan Haas, Yasushi Yatabe, Roman K. Thomas. Functional characterization of recurrent CD74-NRG1 fusions in lung adenocarcinoma. [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 441. doi:10.1158/1538-7445.AM2014-441
Abstract 4411: DRAK1 overexpressed in head and neck cancer suppresses the TGF-β1 tumor suppressor activity in head and neck cancer cells
Authors: Yang Kyung-Min , Kim WonJoo , Lee Jeong-Mi , Kim Seong-Jin 
Published: May 2015

Abstract
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and a highly malignant cancer associated with poor prognosis and low overall survival. Here, we describe a role of DRAK1 (DAP kinase-related apoptosis-inducing kinase 1) in head and neck cancer cells. DRAK1 is significantly overexpressed in primary head and neck tumors and cell lines. Overexpression of DRAK1 decreased the TGF-β1-induced transcriptional activity and expression of tumor suppressor target genes, including p15, p21, whereas DRAK1 silencing enhanced. Furthermore, endogenous depletion of DRAK1 enhanced the TGF-β1-induced cell growth inhibition and suppressed the tumorigenic ability of head and neck cancer cells in vivo. Interestingly, the gain- or loss-of-function of DRAK1 did not change the TGF-β1-induced phosphorylation of Smad2/3. DRAK1 specifically binds to Smad3 through its kinase domain, thereby blocking recruitment of Smad4 and translocation of Smad3 into nucleus. Thus, our findings suggest that aberrant expression of DRAK1 increases tumorigenic potential through the inhibition of TGF-β1 tumor suppressor activity in head and neck cancer cells.
*This work was supported by a National Research Foundation grant of Korea (2009-0081756) funded by the Korea government.
Citation Format: Kyung-Min Yang, WonJoo Kim, Jeong-Mi Lee, Seong-Jin Kim. DRAK1 overexpressed in head and neck cancer suppresses the TGF-β1 tumor suppressor activity in head and neck 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 4411. doi:10.1158/1538-7445.AM2014-4411