bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3053: Knockout of UCP2 suppresses skin carcinogenesis
Authors: Sreedhar Annapoorna , Zhang Chunjing , Zhao Yunfeng 
Published: August 2015

Abstract
Mitochondria are important and necessary components of cell organelles. In recent times, mitochondrial metabolism has regained attention due to the growing evidence suggesting that dysfunction of mitochondria could play a major role in cancer.
Cancer cells that are actively proliferating have great demand for ATP. This huge demand for ATP is met by glycolysis, which is called the ‘Warburg Effect’.
Although the Warburg effect has lately been challenged, dysfunction of the mitochondrial dependent processes is a characteristic feature of almost all tumor cells, which lead to higher oxidative stress, inhibition of apoptosis and enhanced cell proliferation; which are the hallmarks of tumor cells.
Mitochondrial uncoupling proteins have gained enormous interest in the field of cancer metabolism due to their impact on mitochondrial dependent processes.
Uncoupling proteins are a family of mitochondrial proteins present in the inner mitochondrial membrane whose physiological role is to decrease membrane potential and hence ATP production. One of the most interesting functions of UCPs is to decrease the generation of ROS.
However, because of altered mitochondrial dependent processes, cancer cells have elevated levels of ROS production leading to a phenomenon called ‘oxidative stress’. To fight against this oxidative stress, UCP2 (a homologue of UCP family) has shown to be up-regulated in a number of human cancers. However, there is no direct evidence supporting UCP2 contributes to carcinogenesis.
Considering this ability of UCP2 to modulate ROS, membrane potential and mitochondrial bioenergetics, an interesting question to us, was whether UCP2 is involved in the progression of cancer.
Using UCP2 homozygous knockout mice and UCP2 overexpressed cells; our data have demonstrated that knockout of UCP2 suppressed skin carcinogenesis. Overexpression of UCP2 enhanced skin cell transformation and oncogenic activation. In addition, genipin, a known UCP2 inhibitor, was able to inhibit oncogenic activation during skin cell transformation, even in UCP2 overexpressed cells. Finally, although knockout of UCP2 increased the basal levels of protein oxidation, it did not enhance protein oxidation in mouse skin epidermal tissues during skin carcinogenesis.
In summary, our data have provided direct evidence that UCP2 promotes carcinogenesis, and targeting UCP2 may serve as a translational approach for chemoprevention.
Citation Format: Annapoorna Sreedhar, Chunjing Zhang, Yunfeng Zhao. Knockout of UCP2 suppresses skin carcinogenesis. [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 3053. doi:10.1158/1538-7445.AM2015-3053
Abstract 3085: MicroRNA-186 inhibition alters cell proliferation and colony formation in prostate cancer
Authors: Jones Dominique Zilpha , Hobbing Katharine R. , Schmidt M. L. , Clark Geoffrey J. , Kidd LaCreis R. 
Published: August 2015

Abstract
MicroRNAs (miRs), key regulators of cancer-related genes, are dysregulated in many solid tumors, including prostate cancer. However, the role of miR-186 in prostate cancer (PCA) requires further elucidation. Previously, we observed mature miR-186-5p was significantly up-regulated in the serum collected from PCA patients (n = 15) diagnosed with aggressive PCA (stage III/IV) disease compared to disease-free men (n = 5). In addition, miR-186 expression was significantly up-regulated in metastatic PCA cells (PC3) compared to a normal prostate epithelial cell line (RWPE1). Putative and predicted miR-186 gene targets in various cancers include pro-apoptotic and tumor suppression-related genes (e.g., P2×7, FOXO1, AKAP12). We hypothesized that miR-186 inhibition will reduce the aggressive PCA phenotype.
To test this hypothesis, PC3 cells were transiently transfected with miR-186 inhibitor and scramble control for 24hrs. Cell viability and colony formation of transfected cells were evaluated via the ATPlite Luminescence assay and soft agar assay. We also evaluated expression profiles of predicted miR-186 gene targets in PCA cell lines and transiently transfected PC3 cells using qRT-PCR.
Transient inhibition of miR-186 repressed cellular proliferation and colony formation by 48-58% in 72-96hrs and 30% after 21 days, respectively. We observed a 1.6-2.24 fold up-regulation in ROCK1 gene expression in PC3 cells treated with miR-186 inhibitor. However, additional studies are needed to assess whether stable inhibition of miR-186 will increase PCA invasiveness by up-regulating ROCK1 using in vitro assays and murine models. Moreover, predicted miR-186 gene targets require validation using qRT-PCR, western blots and luciferase reporter assays. Such efforts may lead to the identification of novel biomarkers to improve diagnostic, prognostic and clinical management strategies.
Citation Format: Dominique Zilpha Jones, Katharine R. Hobbing, M. L. Schmidt, Geoffrey J. Clark, LaCreis R. Kidd. MicroRNA-186 inhibition alters cell proliferation and colony formation 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 3085. doi:10.1158/1538-7445.AM2015-3085
Abstract 3086: From profiling to function: A role for microRNA miR-888 in promoting prostate cancer progression
Authors: Lewis Holly , Hasegawa Tsuyoshi , Glavich Garrison , Lance Raymond , Semmes O. John , Beydoun Hind , Drake Richard , Esquela-Kerscher Aurora 
Published: August 2015

Abstract
Prostate cancer remains the second leading cause of cancer-related deaths among men in the United States despite the widespread use of prostate specific antigen (PSA) as a diagnostic marker for prostate cancer and as a predictor of treatment outcome. MicroRNAs (MiRNAs) belong to a growing class of small non-coding RNAs that are often abnormally expressed in fluid and tissue specimens from prostate cancer patients compared to non-cancer individuals. These miRNAs are hypothesized to play a direct role in promoting disease progression and metastasis in the prostate and are intensely studied for both their diagnostic and therapeutic potential for human cancer. Our laboratory profiled candidate prostate-cancer associated miRNAs in an innovative prostatic fluid biomarker source called expressed prostatic secretions in urine (EPS urine) to determine their utility as discriminating biomarkers for advanced forms of prostate cancer. 10 out of 50 miRNA tested showed statistically significant differences in expression between cancer and non-cancer patient groups within the supernatant but not pellet fractions of whole EPS urine. We are investigating if differential miRNA expression in EPS supernatant is due to exosomal populations and how miRNA-loaded exosomes modulate prostate tumorigenesis in mice. Our profiling studies identified miR-888 as a novel factor that correlates with advanced prostate cancer in human prostate cancer cell lines, EPS urine, and primary tumors. Functional assays revealed that miR-888 promotes proliferation, migration, and colony formation of hormone-refractory and androgen-sensitive human prostate cancer cells. Our working model is that miR-888 overexpression in the diseased prostate suppresses SMAD4, RBL1, and TIMP2 targets leading to tumor progression and metastasis. Human miR-888 belongs to a genomic cluster of seven miRNAs on human chromosome Xq27.3. We are currently testing how this miR-888 cluster interacts within a growing network of coding and non-coding genes to regulate prostate tumor progression. This research will provide a better understanding how prostate tumor cells progress to a more metastatic, aggressive state and facilitate the development of more effective diagnostic and therapeutic strategies for this prevalent and deadly disease.
Citation Format: Holly Lewis, Tsuyoshi Hasegawa, Garrison Glavich, Raymond Lance, O. John Semmes, Hind Beydoun, Richard Drake, Aurora Esquela-Kerscher. From profiling to function: A role for microRNA miR-888 in promoting prostate cancer progression. [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 3086. doi:10.1158/1538-7445.AM2015-3086
Abstract 3104: Molecular features that determine the sensitivity of cancer cells to abemaciclib, an inhibitor of CDK4 and CDK6
Authors: Gong Xueqian , Chio Li-Chun , Lallena MaryJo , Merzoug Farhana , Chu Shaoyou , Webster Yue , Dempsey Jack , Ma Xiwen , De Dios Alfonso , Beckman Richard , Buchanan Sean G. 
Published: August 2015

Abstract
It is well established that phosphorylation of Rb-family pocket proteins by CDK4 and CDK6 is important for the commitment of cancer cells to a new cell cycle and the initiation of the G1-S phase transition. Abemaciclib is a potent inhibitor of the kinase activity of both CDK4 and CDK6 and is currently undergoing clinical testing. To better understand the molecular determinants of response to abemaciclib, we tested its anti-proliferative activity across a panel of over 500 well characterized cancer cell lines. Statistical approaches were employed to uncover genomic features associated with the response. Candidate markers of sensitivity and resistance were further tested by genetic manipulations in vitro. In vivo models representing the candidate molecular marker of sensitivity were identified and drug efficacy examined.
Three broad classes of response were identified. The class of tumors cells most resistant to abemaciclib showed enrichment for RB1 mutations. Conversely, cell lines with amplification of CCND2 and CCND3 were among the very most sensitive tumor cells and tumor cells with these markers showed evidence of senescence and apoptosis after either depletion of the cognate D-cyclin or treatment with abemaciclib. In vivo models of tumors harboring CCND2 and CCND3 gene amplification were very sensitive to abemaciclib treatment and showed evidence of tumor regression.
Citation Format: Xueqian Gong, Li-Chun Chio, MaryJo Lallena, Farhana Merzoug, Shaoyou Chu, Yue Webster, Jack Dempsey, Xiwen Ma, Alfonso De Dios, Richard Beckman, Sean G. Buchanan. Molecular features that determine the sensitivity of cancer cells to abemaciclib, an inhibitor of CDK4 and CDK6. [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 3104. doi:10.1158/1538-7445.AM2015-3104
Abstract 3110: Urinary miR-1825 and miR-484: An oncogene and a tumor- suppressor gene among prostate cancer patients
Authors: Abdalla Moemen , Haj-Ahmad Taha A. , Haj-Ahmad Yousef 
Published: August 2015

Abstract
MicroRNAs (miRNAs) are short, single-stranded RNA molecules with the ability of acting as post-transcriptional regulators of gene expression. MiRNAs regulate a number of important pathways, such as: cellular differentiation, proliferation, and apoptosis. MiRNA expression profiling patterns were demonstrated to have more potential than the common mRNA expression profiling for the characterization of poorly differentiated tumours. Studying miRNA expression profiles “signatures” will help in understanding the role of these miRNAs in the process of cancer development. The aim of this study was to profile the urinary miRNA expression signatures among prostate cancer patients in comparison to healthy male individuals. To identify the miRNA signatures specific for PCa, total RNA was isolated from 2.5mL of urine from all prostate cancer patients and from healthy males. RNA isolated from each group were pooled together and the differential expression analysis of miRNAs between the pooled samples was performed using MiRNA Microarray technology. Differential expression of two individual miRNAs, miR-1825 and miR-484, was observed between healthy males and prostate cancer patients. The relative expression of these two miRNAs were assessed among among the prostate cancer group and the healthy male group using RT-qPCR. MiR-1825 was up-regulated in seven out of eight PCa samples (88%), whereas miR-484 was down-regulated in six out of the eight PCa samples (75%). It has been found that the putative target for miR-1825 is member-1 of the Discoidin Domain family of Receptors (DDR1). The over-expression of DDR1 was reported to be a prognostic marker for the poor survival in several cancer types and therefore is proposed that miR-1825 might function as a tumor-suppressor by normally or in response to cancer, inhibiting DDR1's translation. As for miR-484, E3 ubiquitin-protein ligase (UBR5), which is thought to be involved with DNA repair, has been found to be the putative target for miR-484. It has be reported that the over-expression of a mutated version of UBR5 was found in breast and ovarian cancers where its deregulation was cited as a possible cause of malignant progression. It is therefore being proposed that miR-484 might function as a tumor- suppressor whereby its expression controls progression via the regulation of genes, such as UBR5, that have already been potentially associated with cancer progression.
Citation Format: Moemen Abdalla, Taha A. Haj-Ahmad, Yousef Haj-Ahmad. Urinary miR-1825 and miR-484: An oncogene and a tumor- suppressor gene among prostate cancer patients. [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 3110. doi:10.1158/1538-7445.AM2015-3110
Abstract 3111: JNK/c-Jun- and NF-κB-mediated microRNA-221 governs tumor suppressor HDAC6 to potentiate malignant progression of liver cancer
Authors: Kim Hyung Seok , Shen Qingyu , Eun Jung Woo , Shin Woo Chan , Yang Hee Doo , Park Won Sang , Lee Joung Young , Nam Suk Woo 
Published: August 2015

Abstract
Many clinical studies of cancer patients have established that the most common reason behind changes in HDAC function is its overexpression. However, among HDACs in liver cancer, HDAC6, a cytoplasmic tubulin deacetylase, is uniquely endowed with a tumor suppressor, but the mechanism underlying HDAC6 inactivation has yet to be uncovered. In this study we show that genetic and epigenetic dysregulation was not part of the HDAC6 inactivation mechanism. Instead, microRNA-221-3p (miR-221) directly suppressed HDAC6 in hepatocellular carcinoma (HCC) cells. A comprehensive miRNA profiling analysis identified seven putative endogenous miRNAs that are significantly upregulated in HCC. Ectopic expression of miRNA mimics in Dicer knockdown cells evidenced miR-221 to suppress HDAC6 in HCC cells. Notably, targeted-disruption of miR-221 repressed cancer cell growth and proliferation, and it recapitulated HDAC6 overexpression effects in HCC cells. Our results also demonstrate that c-Met-mediated c-Jun NH2-terminal kinase (JNK)/c-Jun signaling induced miR-221 to suppress HDAC6 and was sustained in liver cancer cells but not in normal hepatic cells. In addition, cytokine-induced NF-κBp65 independently regulated miR-221, thereby suppressing HDAC6 expression in liver cancer cells. HCC tissues derived from chemical-induced rat liver cancer models validated that JNK/c-Jun activation and NF-kBp65 nuclear translocation are essential for the transcriptional activation of oncogenic miR-221 to repress tumor suppressor HDAC6 in HCC. In conclusion, our finding suggest that the functional loss or suppression of the tumor suppressor HDAC6 is caused by miR-221 through coordinated JNK/c-Jun- and NF-κB-signaling pathways during liver tumorigenesis, providing a novel target for the molecular treatment of liver malignancies.
Citation Format: Hyung Seok Kim, Qingyu Shen, Jung Woo Eun, Woo Chan Shin, Hee Doo Yang, Won Sang Park, Joung Young Lee, Suk Woo Nam. JNK/c-Jun- and NF-κB-mediated microRNA-221 governs tumor suppressor HDAC6 to potentiate malignant progression of liver 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 3111. doi:10.1158/1538-7445.AM2015-3111
Abstract 3114: MicroRNA-205 signaling regulates mammary stem cell fate and tumorigenesis
Authors: Wu Meng-Ju , Chang Chun-Ju 
Published: August 2015

Abstract
Dysregulation of epigenetic controls is associated with tumorigenesis in response to microenvironmental stimuli; however, the regulatory pathways involved in epigenetic dysfunction are largely unclear. We have determined that a critical epigenetic regulator, microRNA-205 (miR-205), is repressed by the ligand jagged1, which is secreted from the tumor stroma to promote a cancer-associated stem cell phenotype. Knockdown of miR-205 in mammary epithelial cells promoted epithelial-mesenchymal transition (EMT), disrupted epithelial cell polarity, and enhanced symmetric division to expand the stem cell population. Furthermore, miR-205-deficient mice spontaneously developed mammary lesions, while activation of miR-205 markedly diminished breast cancer stemness. These data provide evidence that links tumor microenvironment and microRNA-dependent regulation to disruption of epithelial polarity and aberrant mammary stem cell division, which in turn leads to an expansion of stem cell population and tumorigenesis. This study elucidates an important role for miR-205 in the regulation of mammary stem cell fate, suggesting a potential therapeutic target for limiting breast cancer genesis.
Citation Format: Meng-Ju Wu, Chun-Ju Chang. MicroRNA-205 signaling regulates mammary stem cell fate and 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 3114. doi:10.1158/1538-7445.AM2015-3114
Abstract 3119: miR-296-5p and miR-874-3p control cell proliferation and apoptosis in HCC via regulation of PIN1 expression
Authors: Leong Ka Wai , Cheng Chi Wai , Wong Chun Ming , Ng Oi Lin Irene , Kwong Yok Lam , Tse Eric Wai Choi 
Published: August 2015

Abstract
Introduction: PIN1 is a peptidyl-prolyl cis/trans isomerase (PPlase) that regulates multiple signaling pathways to control cell fate. It is found to be up-regulated in hepatocellular carcinomas (HCC), leading to increased cell proliferation and inhibition of apoptosis. However, the regulation of PIN1 remains poorly defined. MicroRNA (miRNA) plays a pivotal role in carcinogenesis by regulating tumor suppressor genes and oncogenes via targeting the 3′UTR of their encoded mRNAs. Therefore, we aimed at identifying miRNAs regulating PIN1 expression, and determining the contributions of these miRNAs to tumorigenesis through PIN1.
Methods: Potential miRNAs regulating PIN1 were identified through sequence prediction using the online database TargetScan Release 6.2. Western immunoblotting and qRT-PCR were used to assess PIN1 expression in HCC cells with over-expression of identified miRNAs. Dual-Luciferase reporter assay was conducted to examine the direct interaction between the identified miRNAs and PIN1 3′UTR. The tumor suppressive role of the identified miRNAs in HCC cells was investigated using MTT cell proliferation assay, colony formation assay and Annexin V apoptosis detection assay. To investigate the correlation between the levels of PIN1 and the identified miRNAs, qRT-PCR was used to determine the mRNA levels of PIN1 and the identified miRNAs in 20 pairs of normal liver tissue and HCC.
Results: We identified miR-296-5p and miR-874-3p as important negative regulators of PIN1. Consequently, over-expression of miR-296-5p and miR-874-3p enhanced cellular apoptosis, and inhibited cell growth and colony formation in HCC cells. Furthermore, the cellular functions of miR-296-5p and miR-874-3p were abrogated by over-expression of PIN1. Importantly, the expression of PIN1 was negatively correlated with that of miR-296-5p and miR-874-3p in HCC tissues, consistent with the regulatory role of miR-295-5p and miR-874-3p on PIN1 expression.
Conclusion: Taken together, our data showed that miR-296-5p and miR-874-3p controlled cell proliferation and apoptosis in HCC by regulating PIN1 expression.
Citation Format: Ka Wai Leong, Chi Wai Cheng, Chun Ming Wong, Oi Lin Irene Ng, Yok Lam Kwong, Eric Wai Choi Tse. miR-296-5p and miR-874-3p control cell proliferation and apoptosis in HCC via regulation of PIN1 expression. [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 3119. doi:10.1158/1538-7445.AM2015-3119
Abstract 3120: miR-489 function as tumor suppressor miRNA by targeting HER2 in HER2-positive breast cancer
Authors: Patel Yogin , Shah Nirav , Botbyl Racheal , Lee Jishin , Chen Hexin 
Published: August 2015

Abstract
Human epidermal growth factor receptor 2 (HER2) is a receptor tyrosine kinase overexpressed in 20-30% of all breast cancer and associated with poor prognosis and outcome. Previous studies have shown that dysregulation of several micro RNAs (miRs), play a key role in breast cancer progression and metastasis. In this study, we evaluated ∼330 miRs, to find specific miRs dysregualted by HER2 signaling. After further screening we focused our study on miR-489, whose expression was ∼6-7 fold downregulated specifically by HER2 signaling. Restoration of miR-489 expression in several HER2-positive breast cancer cell lines resulted in increased cell death and cell cycle arrest. To investigate the molecular mechanism of action of miR-489, we studied effect of miR-489 on HER2 signaling pathway and found that higher expression of miR-489 led to the decreased levels of HER2 (both mRNA and protein) and decreased Akt activation. Furthermore, we for the first time demonstrated that HER2 is a direct target of miR-489 and therefore HER2 and miR-489 signaling pathways form a mutual regulatory loop. To further demonstrate clinical relevance of miR-489, we analyzed both normal and tumor human breast tissue samples using Fluorescent in situ hybridization technique (FISH). Our imaging data indicated that miR-489 is expressed at much lower level in tumor tissues compared to that of the normal breast tissue. Overall, our data indicates that miR-489 acts as a tumor suppressor miR at least partially by directly targeting HER2 in HER2 positive breast cancer cells.
Citation Format: Yogin Patel, Nirav Shah, Racheal Botbyl, Jishin Lee, Hexin Chen. miR-489 function as tumor suppressor miRNA by targeting HER2 in HER2-positive 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 3120. doi:10.1158/1538-7445.AM2015-3120