bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1942: Identification of a microRNA expression signature for radiochemosensitivity of colorectal cancer cells, involving miRNAs-320a, -224, -132 and let7g.
Authors: Salendo Junius , Spitzner Melanie , Kramer Frank , Jo Peter , Beissbarth Tim , Wolff Hendrik A. , Becker Heinz , Dobbelstein Mathias , Ghadimi Michael , Grade Marian , Gaedcke Jochen 
Published: August 2014

Abstract
Background: Preoperative 5-fluorouracil-based chemoradiotherapy is the standard treatment for locally advanced rectal carcinomas. However, the individual tumor response is very heterogeneous, ranging from complete resistance to regression. Therefore, ascertaining the role of microRNAs (miRNAs) in therapy response as well as identification certain miRNA as predictive markers for response remains very crucial.
Materials/Methods: Using an in-vitro model of 12 colorectal cancer cell lines, we compare the pretherapeutic miRNA expression profiles of these cell lines with the previously assessed radiochemoresistance of each cell lines, respectively. Differences in treatment sensitivity of the cell lines and miRNAs expression were then correlated. Colony formation assays in two independent cell lines were used for the functional validation in-vitro. To asses the clinical applicability miRNA expressions of 64 pretherapeutic biopsies from patients with locally advanced cancer treated with 5-FU based RCT were analyzed.
Results: We identified 36 miRNAs whose expression levels correlated significantly with the heterogeneous sensitivity of the cell lines to chemoradiotherapy (p &lt; 0.05). Microarray measurements were independently validated using semi-quantitative real-time PCR. miR-320, miR-132, miR-429, miR-224 and let-7g were then functionally validated in-vitro by transfection of corresponding miRNA mimics. Analysis of miRNA expression in rectal cancer patients biopsies showed high correlation of miR-224 expression with poor prognosis (p=0.043).
Conclusion: We identified 36 miRNAs that associated with response to chemoradiotherapy. Functional validations of miR-320, miR-132, miR-429, miR-224 and let-7g have been undertaken in-vitro underlining the regulatory effects of the specific miRNAs. Further miR-224 found out to be significantly correlated to Disease Free Survival (DFS). An independent prospective validation in a clinical trial will be performed.
Citation Format: Junius Salendo, Melanie Spitzner, Frank Kramer, Peter Jo, Tim Beissbarth, Hendrik A. Wolff, Heinz Becker, Mathias Dobbelstein, Michael Ghadimi, Marian Grade, Jochen Gaedcke. Identification of a microRNA expression signature for radiochemosensitivity of colorectal cancer cells, involving miRNAs-320a, -224, -132 and let7g. [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 1942. doi:10.1158/1538-7445.AM2013-1942
Abstract 1943: miR-148a overexpression reduces TRAIL resistance and tumorigenesis in NSCLC.
Authors: Joshi Pooja , Garofalo Michela , Croce Carlo M. 
Published: August 2014

Abstract
Non-small cell lung cancer (NSCLC) is the leading cause of death from cancer throughout the world. Although some advances have been made in lung cancer therapy, patient survival is still poor. Tumor-necrosis factor related apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis in malignant cells without inducing significant toxicity in normal cells. However, several carcinomas, including lung cancer, remain resistant to TRAIL. MicroRNAs (miRNAs) are small non-coding RNAs of ∼24 nt that can block mRNA translation and/or negatively regulate its stability. miRNAs are often aberrantly expressed in cancer and their function is linked to the regulation of oncogenes and/or tumor suppressor genes involved in cell signaling pathways. Several miRNAs have been implicated in increasing susceptibility or resistance to TRAIL-induced apoptosis by inhibiting key functional proteins.
In order to identify the miRNAs involved in TRAIL resistance in NSCLC, we evaluated the differential expression of miRNAs in H460 sensitive cells compared with H460R cells that have acquired TRAIL-resistance. MiR-148a was the most downregulated miR in the acquired resistant cells compared to the sensitive cells. Treatment of NSCLC cells with TRAIL after miR-148a overexpression decreased cell viability and increased apoptosis. Furthermore, miR-148a overexpression induced downregulation of matrix metalloproteinase 15 (MMP15) and Rho-associated kinase 1 (ROCK1) by targeting their 3’ untranslated regions as analysed by Western blot and luciferase reporter assay. Previous studies have shown that MMP15 acts as an anti-apoptotic factor involved in TRAIL resistance in cancer cells. Both, MMP15 and ROCK1 have been reported to be activators of tumor invasion and migration. Our preliminary functional studies using small interference RNA (siRNA) knockdowns of these genes in NSCLC cells support these data. A better understanding of the tumor-supressive role of miR-148a could be the key to developing an effective prognostic and therapeutic tool for treating NSCLC.
Citation Format: Pooja Joshi, Michela Garofalo, Carlo M. Croce. miR-148a overexpression reduces TRAIL resistance and tumorigenesis in NSCLC. [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 1943. doi:10.1158/1538-7445.AM2013-1943
Abstract 1952: Deregulated microRNA expression in the progression of salivary gland cancer.
Authors: Zheng Hao , Kiang Alan , Kuo Selena Z. , Rahimy Elham , Wang-Rodriguez Jessica , Ongkeko Weg M. 
Published: August 2014

Abstract
Salivary gland cancer constitutes one of the five main subsets of cancer in the head and neck region. Nonresectable malignant tumors demonstrate a low 20-year survival rate due to radioresistance and a high propensity for metastasis. The molecular mechanisms underlying pathogenesis of salivary cancer remains poorly elucidated, and thus necessitates further investigation. MicroRNAs (miRNA) are small noncoding RNAs that are predicted to regulate up to 30% of protein-encoding genes. Signature miRNA expression profiles have been identified in various malignancies, implicating miRNAs in the progression of human cancer. In order to better understand the role of miRNAs in the progression of salivary cancer, we profiled the miRNA expression levels of normal salivary tissue, benign salivary tumor, and salivary cancer. A total of 17 formalin-fixed paraffin-embedded salivary tissues, including 4 normal, 4 pleomorphic adenoma (PA), 3 squamous cell carcinoma (SCC), 3 mucoepidermoid carcinoma (ME) and 3 adenocarcinoma (AC), were collected and the endogenous expression of 95 miRNAs was analyzed by microarray. A large number of miRNAs were observed to be aberrantly expressed and generally down-regulated in salivary cancer and salivary tumor tissues with respect to normal salivary gland tissues. An unsupervised clustering and a student t-test were performed with a threshold p-value less than 0.05, resulting in the identification of 22 miRNAs differentially expressed at a statistically significant level. Eight candidate miRNAs were selected and further validated by RT-qPCR. The results suggest three miRNAs in SCC (miR-200a, let-7-family, and miR-192) and three miRNAs in AC (miR-107, miR-15b and miR-200a) to be highly involved in the carcinogenetic process of salivary cancers. Furthermore, the up-regulated expression pattern of miR-203 is indicative of a tumorigenetic function in salivary tumors. Interestingly, miR-200b was found to be consistently and significantly down regulated (p=0.01, 19.03 fold decrease) in the three types of salivary cancer under investigation. Recent studies have implicated miR-200b in EMT and invasion in cancer cells by directly targeting E-cadherin transcriptional repressors. The miRNAs identified in this study may serve as potential biomarkers and targets for future miRNA based therapy.
Citation Format: Hao Zheng, Alan Kiang, Selena Z. Kuo, Elham Rahimy, Jessica Wang-Rodriguez, Weg M. Ongkeko. Deregulated microRNA expression in the progression of salivary gland 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 1952. doi:10.1158/1538-7445.AM2013-1952
Abstract 1953: Rapid quantitation of circulating microRNAs using a novel detection technology.
Authors: Duelli Dominik , Palma Jaime , Weldon Don , Doong Justin , Johnston Grace , Stacey Fellars , Hastings Michelle 
Published: August 2014

Abstract
The rapid implementation of quantifying microRNAs (miRNAs) in body fluids for diagnosis and prognosis could be improved by designing more rapid approaches. The current mainstream approach is quantitative reverse transcriptase PCR (qRT-PCR). Barriers for the applicability are lengthy time requirement for isolation and amplification of miRNAs, and polymerase inhibitors that copurify with miRNA, and compromise the accuracy of the approach. Here we provide an approach using a nano-particle technology that overcomes these limitations. This technology is based on the principle that a fluorophore-containing oligonucletide sequence is fluorescently silent unless displaced from a quencher by a specific substrate RNA. Once displacement occurs, the resulting fluorescence provides a measure of RNA concentration in the reaction. Our approach allows for the direct and rapid quantification of circulating miRNAs with minimal processing of blood plasma/serum and is done without the use of enzymes. Using circulating miRNAs with established roles in cancer and quality control, miR-16, miR-21 and miR-22 and miR-451, we identified optimal temperature, detergent and solvent-extraction parameters, to quantify accurately these miRNAs in plasma using a microplate fluorometer within an hour after plasma preparation. The stringency of our conditions can discriminate wild type from a single-basepair mismatch RNA, and is specific for mature miRNAs. Furthermore, this approach facilitates measurement of samples collected in heparin, an anticoagulant that severely inhibits polymerases used for qRT-PCR. This approach creates the possibility for rapid blood tests to quantify miRNA-associated events in real-time, and provides greater public access to miRNA studies by reducing the cost and time requirement of current accurate approaches of miRNA quantitation.
Citation Format: Dominik Duelli, Jaime Palma, Don Weldon, Justin Doong, Grace Johnston, Fellars Stacey, Michelle Hastings. Rapid quantitation of circulating microRNAs using a novel detection technology. [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 1953. doi:10.1158/1538-7445.AM2013-1953
Abstract 1957: MiR-200c can mediate either poor or good outcome in ovarian cancer depending on HuR localization in the cell.
Authors: Prislei Silvia , Martinelli Enrica , Mariani Marisa , Raspaglio Giuseppina , Sieber Steven , Ferrandina Gabriella , Shahabi Shohreh , Scambia Giovanni , Ferlini Cristiano 
Published: August 2014

Abstract
MicroRNAs (miRNAs) in solid malignancies can behave as predictors of either good or poor outcome. This is the case with members of the miR-200 family, which are the primary regulators of the epithelial to mesenchymal transition and have been reported to act as both oncogenes and tumor suppressors in independent studies. Expression of miR-200c was assessed in a panel of ovarian cancer cell lines with inherent or acquired drug-resistance. Luciferase reporter assay and ribonucleic-immuno-precipitation assay was used to in vitro characterise the complexes between miR-200c, HuR and class III β-tubulin (TUBB3). Nanofluidic technology and immunohistochemistry were used to analyze the expression of HuR, TUBB3 and miR-200c in 220 ovarian cancer patients. Using such approach, we demonstrated that overexpression of miR-200c in ovarian cancer resulted in poor or good outcome depending on interaction with the RNA binding protein HuR. When the localization of HuR was confined in the nucleus, high expression of miR-200c suppressed class III β-tubulin (TUBB3) expression and resulted in a good prognosis, whereas when HuR occurred in cytoplasm, the same miRNA enhanced TUBB3 expression and produced a poor outcome. Indeed, in an ovarian cancer cell line model, the miR-200c increased HuR binding on TUBB3 mRNA in stressing microenvironmental conditions. This study demonstrated how the prognostic power of a single factor can depend on interactions with additional factors. Through a multidimensional analysis of all components, the actual mechanism(s) underlying the aggressive biological behavior of ovarian cancer can be unraveled, and the prognosis of ovarian cancer patients can be rendered based on rational explanations.
Citation Format: Silvia Prislei, Enrica Martinelli, Marisa Mariani, Giuseppina Raspaglio, Steven Sieber, Gabriella Ferrandina, Shohreh Shahabi, Giovanni Scambia, Cristiano Ferlini. MiR-200c can mediate either poor or good outcome in ovarian cancer depending on HuR localization in the cell. [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 1957. doi:10.1158/1538-7445.AM2013-1957
Abstract 1958: Disregulation of TARBP-2 dependent miRNA maturation : A potential new therapeutic target in Ewing sarcoma..
Authors: De Vito Claudio , Riggi Nicolo , Cornaz Sandrine , Stamenkovic Ivan 
Published: August 2014

Abstract
We have recently shown that microRNAs (miRNAs) play essential roles is the generation of the cancer stem cell (CSC) phenotype in Ewing sarcoma familly tumors (ESFT). Here we compared the miRNA expression profile of ESFT CSCs to that of embryonic stem cells and CSCs from different tumor, which seem to be shared by these different cell types. Our data suggests that the mechanisms implicated in the miRNAs CSC signature rely on a reversible TARBP-2 dependent miRNA maturation defect. Restoration of TARBP2 activity either through chemical compounds or systemic delivery of synthetic forms of two of its targets, miRNA-143 or miRNA-145, inhibited ESFT CSC growth in vitro and in vivo. Taken together our observations provide new therapeutic strategies through restoration of normal miRNA expression profile, inhibiting CSC self-renewal and tumor maintenance.
Citation Format: Claudio De Vito, Nicolo Riggi, Sandrine Cornaz, Ivan Stamenkovic. Disregulation of TARBP-2 dependent miRNA maturation : A potential new therapeutic target in Ewing sarcoma. [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 1958. doi:10.1158/1538-7445.AM2013-1958
Abstract 1963: Prognosis-related miRNA expression profiles of neuroblastoma.
Authors: Ohira Miki , Isogai Eriko , Nakamura Yohko , Kamijo Takehiko , Nakagawara Akira 
Published: August 2014

Abstract
PURPOSE: Neuroblastoma (NB) is known to exhibit clinical heterogeneity and its accurate risk classification is one of the major challenges to improve the personalized therapy. We have been constructing the genomic/genetic profile-based risk classification system for NB. Recent studies indicated that miRNA expression levels are strongly correlated with patient prognosis of NB. To further improve our tumor stratification system by adding the miRNA classifier, we conducted miRNA expression profiling of favorable (F) and unfavorable (UF) NBs and searched for the prognosis-related miRNAs in our sample set.
METHODS: 48 primary samples (19 stage 1 or 2; 16 stage 3 or 4 without MYCN amplification; 13 stage 3 or 4 with MYCN amplification) were analyzed by miRNA microarray (Agilent G4470A). Statistical analysis was conducted by using the information of patient outcome at 3 years after diagnosis. Quantitative RT-PCR (qRT-PCR) was also conducted to validate the results in 101 primary tumors by using Taqman microRNA assays.
RESULTS: Among the 470 miRNAs analyzed, 79 miRNAs showed strong correlation to the prognosis (p&lt;0.05): 17 and 62 miRNAs showed higher expressions in UF and F phenotypes, respectively. In the former miRNA group, 5 were located in 1q whose genomic copy number is frequently increased in UF type tumors. On the other hand, the latter includes 5, 6 and 9 miRNAs in 1p, 19q13 and 14q32, respectively, which are frequently decreased in copy numbers in UF type. In addition, miR-542-5p, whose expression has been reported as a prognostic marker by other groups, was also in the latter group in our dataset (p&lt;0.001, 3.3-fold lower in UF). We further conducted qRT-PCR of these picked-up miRNAs with 101 independent NB samples for validation and found that higher expression of miR-181b and miR-149 showed significant correlation with poor and good prognosis of patients (both logrank p&lt;0.001), respectively. In addition, intermediate-risk type of tumors (stage 3 or 4, no MYCN amplification, n=40) were also significantly classified into favorable or unfavorable by these two miRNA classifiers (p=0.021 and p=0.005, respectively). Interestingly, miR-149 has been reported that it has pro-apoptotic function by repressing Akt1 and E2F1 expressions in a neuroblastoma cell line.
CONCLUSION: The result suggested that miRNA expression profile exhibited strong correlation with NB prognosis, and integration of miRNA classifier with other markers could improve the prediction system for NB prognosis.
Citation Format: Miki Ohira, Eriko Isogai, Yohko Nakamura, Takehiko Kamijo, Akira Nakagawara. Prognosis-related miRNA expression profiles of neuroblastoma. [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 1963. doi:10.1158/1538-7445.AM2013-1963
Abstract 1969: The potential tumor-suppressive role of Krüppel-like factor 9 in colorectal cancer.
Authors: Brown Adam R. , Van Trang T. , Simmen Rosalia C.M. , Simmen Frank A. 
Published: August 2014

Abstract
Colorectal cancer (CRC) remains the third leading cause of cancer-related deaths in the United States. Recent attention has focused on several members of the Krüppel-like family (KLF) of transcription factors in pathogenesis of CRC. Published studies in mouse models have demonstrated that Krüppel-like Factors (KLF) 4 and 6 are important suppressors, while KLF5 is a promoter of CRC development and growth. Our and other laboratories have implicated KLF9 as another KLF with putative tumor-suppressive roles in colon and rectum. However, a causal role for KLF9 as a tumor suppressor has not been evaluated in vivo. In the present study, we generated C57BL/6J mice with two (wild-type, WT) and one (heterozygous, HET) Klf9 alleles within the ApcMin/+ model of intestinal cancer. At 16 weeks of age, male (by 2.5-fold, P=.0015) and female (by 1.5 fold, P=.002) Klf9 HET mice exhibited more colon tumors than WT (n=13-20 mice per gender/genotype). Further, HET females, but not males, showed increased (P=.011) colon tumor incidence compared to WT. Moreover, male HET exhibited greater numbers (P=.03) of large (&gt;3mm diameter) colon tumors while corresponding female HET only showed a trend (P=.099), compared to WT. No significant difference was observed in the number of small intestine tumors in either males or females. Mean colon tumor size between genotypes of either sex was also comparable. Mice of both genotypes did not differ in body weights within specific female and male groups. Excised colon tumors and matched mucosa from male mice were embedded and subjected to immunohistochemistry. No significant differences in immunostaining intensity for β-Catenin were found in tumors nor in matched mucosa between the genotypes. A similar lack of differences in immunostaining for Lgr5, a surface marker for intestinal stem cells was noted in tumors or mucosa between the two genotypes. Since the ApcMin/+ model of intestinal cancer normally displays greater numbers of tumors in the small intestine than in the colon, results suggest a colon-specific contribution of KLF9 loss-of-expression to tumor development. Further, given that KLF9 is a unique thyroid hormone-inducible KLF family member, our results implicate the possible use of thyroid hormone or thyroid hormone receptor agonists in the prevention and/or treatment of CRC. Our collective findings provide early evidence for a tumor-suppressive role of KLF9 in the colon and rectum, the mechanism of which warrants further investigation. Supported by 1F31CA165665-01 and NIH RO1 CA136493.
Citation Format: Adam R. Brown, Trang T. Van, Rosalia C.M. Simmen, Frank A. Simmen. The potential tumor-suppressive role of Krüppel-like factor 9 in colorectal 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 1969. doi:10.1158/1538-7445.AM2013-1969
Abstract 1971: Small C-terminal domain phosphatase 1 stabilizes PML to regulate the progression of renal clear cell carcinoma.
Authors: Lin Yu-Ching , Lu Li-Ting , Feng Xin-Hua , Chen Ruey-Hwa 
Published: August 2014

Abstract
The promyelocytic leukemia (PML) protein elicits pleiotropic tumor suppressive functions and is aberrantly degraded in multiple types of human cancers through poorly understood mechanisms. Previous study in our laboratory revealed that CDK1/2-mediated phosphorylation of PML Ser518 is required for targeting PML to Pin1 for prolylisomerization and subsequently to KLHL20-containing ubiquitin ligase complex for ubiquitination and proteasomal degradation. To identify the negative regulators of this PML degradation pathway, we employed a functional genomic approach to search for phosphatases that act on PML Ser518. This study identifies the small C-terminal domain phosphatase 1/2/3 (SCP1/2/3) as PML Ser518 phosphatases. Because these three phosphatases are of structural and functional similarities, we focus on the prototype of this family, SCP1. We show that SCP1 interacts with PML and reduces PML Ser518 phosphorylation levels both in vivo and in vitro. Through this dephosphorylation, SCP1 decreases Pin1-KLHL20 mediated-PML polyubiquitination and prolongs PML half life. Consequently, SCP1 increases the number of PML-nuclear bodies and elevates PML protein abundance in both normoxia and hypoxia conditions. At functional levels, SCP1 overexpression enhances multiple tumor suppressive effects, including promotion of apoptosis and inhibition of cell proliferation and migration. Importantly, all of these effects are reversed by PML knockdown. Clinically, SCP1 expression is downregulated in renal clear cell carcinoma (RCC) and this downregulation correlates with PML downregulation. Restoration of SCP1-mediated PML stabilization inhibits RCC proliferation, migration and transformation. Together, our study identifies SCP1 as a positive regulator of PML by dephosphorylation of PML Ser518 to antagonize the Pin1/KLHL20-dependent PML degradation pathway. Blockage of SCP1/PML axis is manifested in RCC and contributes to RCC progression.
Citation Format: Yu-Ching Lin, Li-Ting Lu, Xin-Hua Feng, Ruey-Hwa Chen. Small C-terminal domain phosphatase 1 stabilizes PML to regulate the progression of renal clear cell carcinoma. [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 1971. doi:10.1158/1538-7445.AM2013-1971