bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3058: miRNA networks mediate the tumor suppressive function of FOXO proteins.
Authors: Nadler Monica , Zabolian Robin , Ndebele Kenneth , bertomeu thierry , Bucur Octavian , Pennarun Bodvael , Khosravi-Far Roya 
Published: August 2014

Abstract
FOXO transcription factors, as regulators of a variety of cellular functions, including promotion of apoptotic cell death, are negatively regulated by various oncogenic signaling cascades and have emerged as bona fide tumor suppressors. Indeed, studies by others and us have shown that the suppression of FOXO function is critical in promoting evasion of apoptosis and is a significant occurrence in several hematological malignancies. Consequently, FOXO proteins signify an important therapeutic target in hematopoietic malignancies as well as other types of cancer, where repression of FOXO plays a key role in malignancy. Since transcription factors are not yet easily “druggable," it is vital to identify mediators of FOXO function that can be readily targeted. It is now apparent that aberrant miRNA expression plays a major role in cell and tissue-specific manner in the pathogenesis of various types of cancers including hematological malignancies. Both miRNA loss of function and miRNA overexpression have been shown to target key cellular proteins and contribute to cancer pathogenesis. Conversely, miRNA genes themselves have been shown to be direct targets of transcription factors that are known as important tumor suppressors or oncogenic proteins. Through a systematic screening approach, we have identified members of three miRNA clusters that are dependent on FOXO transcription factors for expression. We have observed that the level of these miRNAs is dependent on BCR-ABL status of hematopoeitc cells and they their levels are changed in specimens from Leukemia patients. Our studies indicates a mechanism of action for FOXO tumor suppressors whereby members of two miRNA families are direct transcriptional targets of FOXO3. Moreover, these miRNAs target and reduce the expression of two key oncogenic factors, the serine/threonine kinase mTOR, and proto-onocogene c-myc, to keep cell growth at bay and prevent tumorigenesis. Our investigations have unraveled the miRNA arm of the FOXO tumor suppression network.
Citation Format: Monica Nadler, Robin Zabolian, Kenneth Ndebele, thierry bertomeu, Octavian Bucur, Bodvael Pennarun, Roya Khosravi-Far. miRNA networks mediate the tumor suppressive function of FOXO proteins. [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 3058. doi:10.1158/1538-7445.AM2013-3058
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 3068: MicroRNA 4723-5p is novel tumor suppressor microRNA in prostate cancer that directly regulates Abelson family of nonreceptor protein tyrosine kinases.
Authors: Arora Sumit , Saini Sharanjot , Majid Shahana , Shahryari Varahram , Yamamura Soichiro , Chiyomaru Takeshi , Fukuhara Shinichiro , Chang Inik , Deng Guoren , Tanaka Yuichiro , Dahiya Rajvir 
Published: August 2014

Abstract
The Abelson (c-Abl) proto-oncogene encodes a highly conserved nonreceptor protein tyrosine kinase that has been implicated in many cellular processes including regulation of cell growth and survival, oxidative stress and DNA-damage responses, actin dynamics and cell migration. Aberrant activity of this tyrosine kinase has been implicated in the stimulation of cancer growth and progression. Abl tyrosine kinase represents a target for specific anti-cancer therapy in prostate cancer and Abl inhibitors are being tested clinically for the treatment of prostate cancer bone metastasis. Here we report that Abl kinases are regulated by a novel microRNA- miR-4723-5p in prostate cancer. Expression profiling of miR-4723-5p expression in a cohort of prostate cancer clinical specimens showed that miR-4723-5p expression is widely attenuated in prostate cancer. Low miR-4723-5p expression was significantly correlated with poor survival outcome and tumor progression and recurrence in prostate cancer. Further, our analyses suggest that miR-4723-5p has significant potential as a disease biomarker for diagnosis and prognosis in prostate cancer. To evaluate the functional significance of decreased miR-4723-5p expression in prostate cancer, miR-4723-5p was reintroduced in prostate cancer cell lines followed by functional assays. The over expression of miR-4723-5p led to significant decreases in cell growth, clonability, invasion and migration. Importantly, miR-4723-5p reexpression led to dramatic induction of apoptosis in prostate cancer cell lines suggesting that miR-4723-5p is a pro-apoptotic microRNA that regulates prostate carcinogenesis. Analysis of putative miR-4723-5p targets showed that miR-4723-5p targets Integrin alpha 3 (ITGA3) and Methyl CpG binding protein (MeCP2) in addition to Abl1 and Abl2 kinases. In conclusion, we have identified a novel microRNA mediated regulation of Abl tyrosine kinases in prostate cancer. This study suggests that miR-4723-5p may be an attractive target for therapeutic intervention in prostate cancer.
Citation Format: Sumit Arora, Sharanjot Saini, Shahana Majid, Varahram Shahryari, Soichiro Yamamura, Takeshi Chiyomaru, Shinichiro Fukuhara, Inik Chang, Guoren Deng, Yuichiro Tanaka, Rajvir Dahiya. MicroRNA 4723-5p is novel tumor suppressor microRNA in prostate cancer that directly regulates Abelson family of nonreceptor protein tyrosine kinases. [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 3068. doi:10.1158/1538-7445.AM2013-3068
Abstract 3069: Pleiotropic tumor suppressor role of microRNA-34b in prostate cancer.
Authors: Majid Shahana , Dar Altaf A. , Saini Sharanjot , Shahryari Varahram , Arora Sumit , Chang Inik , Yamamura Soichiro , Tanaka Yuichiro , Chiyomaru Takeshi , Fukuhara Shinichiro , Deng Guoren , Carroll Peter R. , Dahiya Rajvir 
Published: August 2014

Abstract
CpG island hypermethylation is one of the most common causes of the loss of tumor-suppressor microRNAs (miRNA) in cancers. Here we show that miR-34b is silenced in human prostate cancer (PCa) and the mechanism is through CpG hypermethylation. We provide evidence that miR-34b directly targets methyltransferases (DNMT) and deacetylases (HDACs). We show that miR-34b expression could predict overall survival and recurrence free survival such that patients with high miR-34b levels had longer survival. Further we elucidate the tumor suppressor role of miR-34b using both in vitro and in vivo models. Functionally miR-34b inhibits cell proliferation, colony formation, migration/invasion and triggers G0/G1 cell cycle arrest and apoptosis in cancer cells. The mechanism is partly through the down regulation of AKT pathway as miR-34b directly targets AKT and causes depletion of its downstream genes. Our results show that over-expression of miR-34b caused a decline in the mesenchymal markers Vimentin, ZO1, N-cadherin and Snail whereas there was an increase in E-cadherin expression. Finally we demonstrated the antitumor effect of miR-34b in vivo. MiR-34b caused a dramatic decrease in tumor growth in nude mice compared to cont-miR. These findings offer new insight into the role of miR-34b in the inhibition of prostate cancer through demethylation, active chromatin modification and AKT pathways and may provide a rationale for the development of new strategies targeting epigenetic regulation of miRNAs for the treatment of prostate cancer.
Citation Format: Shahana Majid, Altaf A. Dar, Sharanjot Saini, Varahram Shahryari, Sumit Arora, Inik Chang, Soichiro Yamamura, Yuichiro Tanaka, Takeshi Chiyomaru, Shinichiro Fukuhara, Guoren Deng, Peter R. Carroll, Rajvir Dahiya. Pleiotropic tumor suppressor role of microRNA-34b in 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 3069. doi:10.1158/1538-7445.AM2013-3069
Abstract 3085: Expression profiling of exosomal miRNAs derived from human esophageal cancer cells by Solexa high-through sequencing.
Authors: Liao Juan , Liu Ran , Yin Lihong 
Published: August 2014

Abstract
Background: Exosomes are small membrane vesicles of endocytic origin that are released into the extracellular environment on fusion of multivesicular bodies (MVB) with the plasma membrane. Studies showed that inside exosomes, cellular gene products including proteins, mRNAs, and microRNAs (miRNAs) are packaged and these molecules can be transferred to recipient cells to deliver their molecular signaling.
Objective: To explore the miRNA expression profile and distribution characteristics of exosomes derived from human esophageal cancer cells by Solexa high-throughput sequencing.
Methods: Exosomes were extracted from cell culture supernatants by ultracentrifugation. Exosomes were identified by transmission electronic microscopy and western blot assay with anti-CD63 antibody. The types and abundance of known and novel miRNAs in cells and exosomes were identified by Solexa high-throughput sequencing.
Results:There were 56421(2.94%) unique sequences in cells and 7727(0.63%) in exosomes matched the known miRNAs(Table 1). 64 in cells and 32 in exosomes novel miRNAs were predicted. Further analysis revealed extensive sequence variations (isomiRs) of cell and exosome miRNAs. The known miRNAs showed an increased expression in cells compared with exosomes. The expression level of hsa-miR-chr15_4885 and hsa-miR-chr18_7463 in exosomes were significantly higher than cells, with an average fold-change of 10 while hsa-miR-chr7_20613 and hsa-miR-chr19_8205 in cells were significantly higher than exosomes, with an average fold-change of thousands.
Conclusion: The miRNA expression profile in exosomes is different from that in cells. It suggested that the significantly enriched miRNAs in exosomes may be the result of an active uptaken by exosomes. These specific miRNAs expressed in exosomes may play an important role in intercellular communication.
Table 1. Distribution of sequence counts for the different classes of small RNAs in cells and exosomes Classification Unique RNA in cells Percentage (%) in cells Unique RNA in exosomes Percentage (%) in exosomes miRNA 56,421 2.94 7,727 0.63 mRNA 59,655 3.11 5,988 0.49 Repbase 31,421 1.64 5,066 0.41 rRNA 260,307 13.56 85,303 6.95 tRNA 80,635 4.20 119,500 9.74 snRNA 27,935 1.45 1,823 0.15 Unknown RNA 1,403,576 73.10 1,001,499 81.63 Total 1,919,950 100.00 1,226,905 100.00
Citation Format: Juan Liao, Ran Liu, Lihong Yin. Expression profiling of exosomal miRNAs derived from human esophageal cancer cells by Solexa high-through sequencing. [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 3085. doi:10.1158/1538-7445.AM2013-3085
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 3086: Modulation of microRNA profile in lung adenocarcinoma cell line following TIMP-1 downregulation.
Authors: Ghoshal-Gupta Sampa , Kutiyanawalla Ammar , Jiwani Shahanawaz , Ojha Juhi , Kolhe Ravindra , Rojiani Amyn M. , Rojiani Mumtaz V. 
Published: August 2014

Abstract
Non-small cell carcinoma accounts for 85% of lung cancer cases and has a 5 year survival rate of only 17%. In recent years, tissue inhibitor of metalloproteinase-1 (TIMP-1) has emerged as an important prognostic marker. In several cancers including non-small cell lung cancer, high serum levels of TIMP-1 have been associated with poor prognosis. Previously, we have shown that overexpressing TIMP-1 in H2009, a lung adenocarcinoma cell line resulted in aggressive tumors when implanted in the mouse brain. In the present study, we have knocked down TIMP-1 expression in the non-small cell lung cancer cell line A549 using shRNA. In vitro assays using the TIMP-1 knockdown clones defined decreased migration in wound assays (p&lt;0.01), as well as reduced invasion (p&lt;0.05) using Boyden chamber assays. We investigated these functional alterations by examining microRNAs in these cell lines. MicroRNAs represent a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level and control crucial signaling and physiological processes functioning either as oncogenes or tumor-suppressors. The miRNA expression profile of A549 cell line and its TIMP1 knockdown clone were evaluated using the Affymetrix miRNA microarray platform on Gene-Chip miRNA 3.0 array in A549 cell line. Following hybridization and data acquisition, we used Partek Genomics Suite ® software for RNA normalization and to determine statistically significant differences in miRNA expression between experimental groups by ANOVA and pairwise comparisons (two-sidedα=0.05). Using the Affymetrix miRNA array we have identified altered miRNAs expression in the clones, with 72 differentially regulated miRNAs following TIMP-1 knockdown. Using quantitative real time PCR we have selectively validated several of the miRNAs that showed the maximal difference. We have confirmed a 2 to 4-fold down regulation of MiR-10b, miR-29a and miR-30 and a 3-fold upregulation of miR-125a-5p. Based on KEGG pathway analysis, this group of validated miRNAs are involved in the MAPK signaling pathway. Western blot analysis showed activation of the apoptosis inducing p38 MAPK pathway in the knockdown clones. Additional mechanistic dissection of these changes and involved pathways will contribute further to our understanding of the role of TIMP-1 in lung cancer. (This research was supported by a Georgia Distinguished Cancer Scholar award to AMR).
Citation Format: Sampa Ghoshal-Gupta, Ammar Kutiyanawalla, Shahanawaz Jiwani, Juhi Ojha, Ravindra Kolhe, Amyn M. Rojiani, Mumtaz V. Rojiani. Modulation of microRNA profile in lung adenocarcinoma cell line following TIMP-1 downregulation. [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 3086. doi:10.1158/1538-7445.AM2013-3086
Abstract 3101: The Role of MYC and the miR-17∼92 cluster in histone deacetylase inhibitor-induced apoptosis.
Authors: Talbert Dominique R. , Wappel Robert L. , Moran Diarmuid M. , Shell Scott A. , Bacus Sarah S. 
Published: August 2014

Abstract
In recent years histone deacetylase inhibitors (HDACi's) have emerged as promising therapeutics for cancer. While favorable responses to HDACi's as single agents have been shown in several hematological malignancies, very little efficacy has been demonstrated in solid tumors. c-Myc (Myc), an oncoprotein commonly over-expressed in cancer, has been shown by several studies to play a critical role in HDACi-mediated cellular death. To expand upon these findings and determine the role that Myc plays in this process in solid tumors, we compared the effect of two HDAC inhibitors, SAHA and LAQ824, on the proliferation of solid tumor cell lines expressing high versus low levels of Myc. We found that cells expressing high levels of Myc were more sensitive to HDACi. In addition, there were significant differences in the type of response to HDACi treatment between the two cell types with prominent apoptosis in cells expressing higher levels of Myc while cell cycle arrest was more commonly observed in cells expressing lower levels of Myc. Interestingly, HDACi reduced the expression of Myc and one of its well-known oncogenic miRNA targets, miR-17∼92 cluster, resulting in an increase in the expression of the master pro-apoptotic protein Bim. We propose that this novel mechanism may play a role in the potent anti-proliferative effects mediated by HDACi. Furthermore, these studies suggest that Myc expression could be used as a predictive biomarker to select patients with solid tumors who may be more responsive to HDACi treatment.
Citation Format: Dominique R. Talbert, Robert L. Wappel, Diarmuid M. Moran, Scott A. Shell, Sarah S. Bacus. The Role of MYC and the miR-17∼92 cluster in histone deacetylase inhibitor-induced apoptosis. [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 3101. doi:10.1158/1538-7445.AM2013-3101
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 3115: Sumoylation enhances the stability of the proto-oncogene EVI1 however negatively regulates its DNA binding and transcriptional activity.
Authors: Singh Sneha , Chakraborty Soumen 
Published: August 2014

Abstract
Aberrant expression of the proto-oncogene EVI1 (Ecotropic virus integration site1) has been implicated not only in lymphoid or myeloid malignancies but also in several other solid tumors like colon, ovarian and breast cancer. Despite its crucial role in oncogenesis, the regulatory factors and mechanisms that control the function of EVI1 are partially known. Post translational modifications play a crucial role in regulating various cellular processes by controlling the function of several proteins. Here we show that EVI1, a transcription factor is post-translationally modified by SUMO1. Indirect immunofluorescence studies revealed that EVI1 and SUMO1 colocalized in the nuclear speckles in the cells transiently transfected with EVI1 and SUMO1 as well as cells that constitutively expresses EVI1. Sumoylation is known to stabilize their target protein which was also observed in case of EVI1 through pulse chase assay with cycloheximide. Reporter gene assay revealed that sumoylation impaired EVI1 mediated transactivation of Bcl-xL and SIRT1 promoters and also reduced the DNA binding efficiency of EVI1 which was confirmed through ChIP assay. PIAS proteins are known as SUMO E3 ligase which enhances the sumoylation of the proteins. PIAS proteins are also known to regulate the function of several proteins independent of its ligase activity. Co-immunoprecipiation assay revealed that EVI1 directly interacts with SUMO E3 ligase PIASy, which was also found to enhance EVI1 sumoylation. Our study also demonstrates that PIASy negatively regulated EVI1 transcription activity which is independent of its ligase activity. Thus PIASy was found to be an interacting partner that regulates the function of EVI1 in sumoylation dependent as well as independent manner. In summary, we present a new modifier of EVI1 which controls its stability and deregulates its transcriptional activity. Further study in context with EVI1-SUMO1-PIASy may give a better idea in understanding the functions and the regulation of EVI1 in normal and diseased cells.
Citation Format: Sneha Singh, Soumen Chakraborty. Sumoylation enhances the stability of the proto-oncogene EVI1 however negatively regulates its DNA binding and transcriptional activity. [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 3115. doi:10.1158/1538-7445.AM2013-3115
Abstract 312: A mouse model of chronic prostatic inflammation using a human prostate cancer-derived isolate of Propionibacterium acnes.
Authors: Biswal Shinohara Debika , Vaghasia Ajay , Yu Shu-Han , Nelson William G. , De Marzo Angelo M. , Yegnasubramanian Srinivasan , Sfanos Karen S. 
Published: August 2014

Abstract
Background: A causative role for infectious agents and chronic inflammation in prostate cancer etiology has been difficult to establish in humans. To study this potential link in an in vivo system, we have developed a mouse model of long-term bacteria-induced chronic inflammation of the prostate using a prostatectomy-derived strain of Propionibacterium acnes that may be of particular relevance to prostate cancer.
Methods: Prostates of C57BL/6J mice were inoculated, via urethral catheterization, with PBS (control) or a strain of P. acnes (PA2) isolated from human prostatectomy tissues. Animals were assessed at 2 days, 1 week, 2 weeks, or 8 weeks post-inoculation via histology and immunohistochemistry (IHC).
Results: PA2 inoculation resulted in severe acute and chronic inflammation confined to the dorsal lobe of the prostate. Chronic inflammatory infiltrates persisted for at least 8 weeks post-inoculation. Inflammatory lesions were associated with an increase in the Ki-67 proliferative index, and diminished Nkx3.1 and androgen receptor (AR) production. Interestingly, the observed response required live bacteria. Additionally, both IHC and in situ hybridization assays for P. acnes indicated a potential intracellular persistence of P. acnes in prostate epithelial cells.
Conclusions: To our knowledge, this is the first mouse model of long-term prostatic inflammation induced by P. acnes, and more generally, any prostatectomy tissue-derived bacterial isolate. This model may serve as a valuable preclinical model of chronic prostatic inflammation that can be used to mechanistically study the link between inflammation and prostate cancer and other prostate disease.
Citation Format: Debika Biswal Shinohara, Ajay Vaghasia, Shu-Han Yu, William G. Nelson, Angelo M. De Marzo, Srinivasan Yegnasubramanian, Karen S. Sfanos. A mouse model of chronic prostatic inflammation using a human prostate cancer-derived isolate of Propionibacterium acnes. [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 312. doi:10.1158/1538-7445.AM2013-312