bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5211: Regulation of SRC kinases by microRNA-3607 located in a frequently deleted locus in prostate cancer
Authors: Saini Sharanjot , Arora Sumit , Majid Shahana , Shahryari Varahram , Tabatabai Laura Z. , Yamamura Soichiro , Tanaka Yuichiro , Dahiya Rajvir , Deng Guoren 
Published: May 2015

Abstract
Genomic studies suggest that deletions at chromosome (chr) 5q region (particularly chr5q14-q23) are frequent in prostate cancer, implicating this region in prostate carcinogenesis. However, the genes within this region are largely unknown. Here we report for the first time, the widespread attenuation of miR-3607 - a microRNA gene located at chr5q14 region- in prostate cancer. Expression analyses of miR-3607 in a clinical cohort of prostate cancer (PCa) specimens showed that miR-3607 is significantly attenuated and low miR-3607 partment of Urology, UCSF School of Mediacinehip and guidance. his guidance. expression is correlated with tumor progression and poor survival outcome in prostate cancer. Our analyses suggest that miR-3607 expression may be a clinically significant parameter with an associated diagnostic potential. We examined the functional significance of miR-3607 in prostate cancer cell lines and found that miR-3607 overexpression led to significantly decreased proliferation, apoptosis induction and decreased invasiveness. Further, our results suggest that miR-3607 directly represses oncogenic SRC family kinases, LYN and SRC, in prostate cancer. In view of our results, we propose that miR-3607 plays a tumor suppressive role in prostate cancer by regulating SRC kinases that in turn regulates prostate carcinogenesis. To our knowledge this is the first report that: (i) identifies a novel role for miR-3607 located in a frequently deleted region of prostate cancer and (ii) defines novel miRNA mediated regulation of SRC kinases in prostate cancer. Since SRC kinases play a central role in prostate cancer progression and metastasis and are attractive targets, this study has potential implications in the design of better therapeutic modalities for prostate cancer management.
Citation Format: Sharanjot Saini, Sumit Arora, Shahana Majid, Varahram Shahryari, Laura Z. Tabatabai, Soichiro Yamamura, Yuichiro Tanaka, Rajvir Dahiya, Guoren Deng. Regulation of SRC kinases by microRNA-3607 located in a frequently deleted locus in prostate 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 5211. doi:10.1158/1538-7445.AM2014-5211
Abstract 5212: Regulation of androgen receptor expression by andro-miRs in prostate cancer
Authors: Ebron Jey Sabith , Sikand Kavleen , Singh Jagjit , Shukla Girish C. 
Published: May 2015

Abstract
Androgen receptor (AR) is a member of the steroid receptor family which plays a significant role in the regulation of both prostate cell proliferation and growth suppression. The targeting of androgen- and AR- signaling axis remains the primary therapeutic option for prostate cancer (PCa) treatment. AR mRNA has a long 3′UTR of 6.8 kb length and is predicted to be a target of many miRNAs. The existence of long 3′UTR proposes a complex mechanism of regulation of AR gene expression through miRNAs and other factors including RNA binding proteins and polyadenylation signals. Differential expression of various miRNAs has been reported to be associated with the progression of the disease to harmone-independence and castration-resistant prostact cancer (CRPC). However, the direct regulation of AR transcriptional activity through miRNAs is not clearly understood. Our lab has discovered that AR is a target of andro-miRs (miR-488*, miR-644, miR-149, miR-512-5p). These andro-miRs bind to target sequences in the 3′UTR of AR and downregulates luciferase expression in the target-validation validation experiments as well as endogeneous AR expression. Our ongoing study of andro-miRs also indicates that, in addition to downregulation of AR gene expression by the action of andro-miRs alone and synergistically, these miRNAs can regulate AR signaling leading to androgen-independence and resistance. This post transcriptional regulation of AR gene expression through andro-miRs makes them an interesting candidate for miR-based adjunctive treatment in CRPC treatment.
Note: This abstract was not presented at the meeting.
Citation Format: Jey Sabith Ebron, Kavleen Sikand, Jagjit Singh, Girish C. Shukla. Regulation of androgen receptor expression by andro-miRs in prostate 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 5212. doi:10.1158/1538-7445.AM2014-5212
Abstract 5213: microRNA-mediated loss of KDM5B expression leads to suppression of the malignant bladder cancer phenotype
Authors: Veerakumarasivam Abhimanyu , Kodiappan Radha , Chan Soon Choy , Razack Azad Hassan Abdul , Ong Teng Aik 
Published: May 2015

Abstract
We recently identified KDM5B as a putative oncogene. The expression of KDM5B correlated with increased cellular proliferative capacity and was found to be overexpressed in many cancers including bladder cancer (BC). KDM5B is a histone demethylase enzyme that modifies chromatin structure to specify cellular transcriptional states. It is a cancer/testis antigen; whereby in normal conditions, expression is limited to early embryonic stages and the testis in adults. Thus, KDM5B is an excellent therapeutic target. Since the expression of KDM5B in embryonic stem cells is orchestrated by miRNAs and that the expression of miRNAs are altered in BC, we hypothesized that miRNAs may be the switch that can abate the expression of KDM5B and thus affect the malignant phenotype of BC cells. This study was aimed at identifying and modulating the expression of miRNAs that are able to regulate KDM5B expression and BC phenotypes. By coupling in silico screens with RT-QPCR analysis of in vitro expression of BC cells of different malignant potential, we predicted several miRNAs as potential regulators of KDM5B transcripts. The functional effects of specific miRNAs on KDM5B expression, cell cycle, proliferation and invasion of BC cells was determined by modulating the expression of these miRNAs using mimics (upregulation) and antagomirs (downregulation). Expression of miR-137 in BC cells was found to be inversely correlated with KDM5B expression. Ectopic overexpression of miR-137 led to the repression of KDM5B expression, reduced cell growth and invasion as well as increased apoptosis of BC cells. In contrast, the downregulation of miR-137 expression led to reverse effects. The expression modulation of miR-137 also affected the expression of other BC-associated genes such as JDP2 and EGR2. While our results suggest that miR-137 can mitigate the KDM5B-associated BC phenotype, further studies on understanding the effect on aberrant histone methylation patterns are warranted.
Citation Format: Abhimanyu Veerakumarasivam, Radha Kodiappan, Soon Choy Chan, Azad Hassan Abdul Razack, Teng Aik Ong. microRNA-mediated loss of KDM5B expression leads to suppression of the malignant bladder cancer phenotype. [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 5213. doi:10.1158/1538-7445.AM2014-5213
Abstract 5215: miR-200b/c/429 sub-family negatively regulating Rho/ROCK signaling pathway and suppresses HCC metastasis
Authors: Wong Chun-Ming , Wei Lai , Au Sandy Leung-Kuen , Au Sandy Leung-Kuen , Fan Dorothy Ngo-Yin , Lee Joyce Man-Fong , Wong Carmen Chak-Lui , Ng Irene Oi-Lin 
Published: May 2015

Abstract
MicroRNAs (miRNAs) are a class of small (∼22 nt) noncoding regulatory RNA molecules that can regulate gene expression by either cleaving or repressing the translation of their mRNA targets. Deregulation of miRNA expression is common in human cancers, including hepatocellular carcinoma (HCC). Recent studies have indicated that the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141 and miR-429) negatively regulates epithelial-mesenchymal transition (EMT) and cell motility by targeting E-cadherin repressors, ZEB1 and ZEB2. However, the roles of the miR-200 family in HCC remain elusive. In this study, we found that miR-200 family was frequently down-regulated in human HCC, which was contributed by the frequently CpG hypermethylation of miR-200 promoters. Functionally, although all miR-200 members suppressed ZEB1/2 expression in HCC, only overexpression of miR-200b/c/429 sub-family impeded HCC cell migration. These findings implied that, in addition to ZEB1/2, other yet unidentified miR-200b/c/429 specific targets may play an important role in HCC metastasis. In silico analyses revealed that miR-200b/c/429 sub-family may have a profound role in modulating cell cytoskeletal reorganization. Along with this notion, we further identified RhoA and ROCK2 as down-stream targets of miR-200b/c/429 sub-family. By using immunofluorescence staining, scanning electron microscope and live cell imaging, we demonstrated that overexpression of miR-200b/c/429 subfamily but not miR-200a/141 sub-family suppressed Rho/ROCK signaling mediated stress fiber and focal adhesion formations, which in turn led to a dramatic cell morphology change and loss of cell migration ability. Furthermore, by employed an orthotopic liver implantation model, we showed that overexpression of miR-200b was sufficient to suppress HCC growth and metastasis in nude mice. Our results together suggest that miR-200b/c/429 sub-family functions as a metastatic suppressor in human HCC by negatively regulating Rho/ROCK signaling pathway.
Citation Format: Chun-Ming Wong, Lai Wei, Sandy Leung-Kuen Au, Sandy Leung-Kuen Au, Dorothy Ngo-Yin Fan, Joyce Man-Fong Lee, Carmen Chak-Lui Wong, Irene Oi-Lin Ng. miR-200b/c/429 sub-family negatively regulating Rho/ROCK signaling pathway and suppresses HCC metastasis. [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 5215. doi:10.1158/1538-7445.AM2014-5215
Abstract 5220: Reciprocal regulation of MYC and LKB1 modulates cell survival and differentiation in lung cancer
Authors: Cortez Maria A. , Yang Chao , Byers Lauren Averett , Diao Lixia , Allen Thaddeus , Giri Uma , Wang Jing , Welsh James , Heymach John Victor 
Published: May 2015

Abstract
MYC and LKB1 are important regulators of cell survival and differentiation. Although recent studies have been shown oncogenic cooperation between MYC and LKB1 loss, their relationship is unclear. In this study, we report a reciprocal regulation between MYC and LKB1 which modulates cell survival and differentiation in non-small cell lung cancer (NSCLC). We found that MYC regulates LKB1 expression via miR-17. Specifically, luciferase activity was reduced in cells transfected with miR-17, LKB1 3′ UTR constructs compared with scrambled control. Mutation of miR-17 interaction sites rescued the luciferase activity, thus confirming that miR-17 directly interacts with the LKB1 3´ UTRs. In agreement with our reporter gene assay results, enforced overexpression of miR-17 decreased the expression of LKB1 mRNA and protein levels compared with scrambled control. Conversely, miR-17 inhibition promoted upregulation of LKB1 expression in NSCLC cells. Furthermore, miR-17 expression was inversely correlated with LKB1 expression in 532 patients with NSCLC from The Cancer Genome Atlas data (TCGA). MYC and miR-17 overexpression promoted mTOR pathway activation, increased cell proliferation and colony formation in NSCLC cells. In line with these findings, similar results were obtained when we knockdown LKB1 expression, suggesting that MYC promotes mTOR pathway and cell survival, at least in part, via LKB1 regulation. Reciprocally, we found upregulation of MYC expression in NSCLC cell lines with LKB1 mutation or low expression compared to LKB1 wild-type (total n=78) via reverse phase protein array (RPPA) analysis. We validated these findings by analyzing MYC expression via western blotting in LKB1-knockdown and LKB1-ovexpressing stable cell lines. Mechanistically, we found that LKB1 downmodulates MYC expression via Yes-Associated protein 1 (YAP) phosphorylation at Ser127 site, which results in YAP cytoplasmic retention inhibiting transcription activation of its targets. In addition, we found that LKB1 also regulates ID2, a negative regulator of cell differentiation, via YAP/MYC axis. Taken together, our study reveals a reciprocal regulation between MYC and LKB1 offering additional mechanistic insights how MYC promotes cell survival and differentiation in lung cancer.
Citation Format: Maria A. Cortez, Chao Yang, Lauren Averett Byers, Lixia Diao, Thaddeus Allen, Uma Giri, Jing Wang, James Welsh, John Victor Heymach. Reciprocal regulation of MYC and LKB1 modulates cell survival and differentiation in lung 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 5220. doi:10.1158/1538-7445.AM2014-5220
Abstract 5223: Prognostic value of microRNA signature in non-small-cell lung cancer: A microRNA expression analysis
Authors: Pu Heng-Ying , Fu Da , Zhang Mei-Yin , Cha Yin-Lian , Peng Hai-Shan , Zhang Lan-Jun , Jia Wei-Hua , Zeng Yi-Xin , Liu Wan-Qing , Zheng Steven X.F. , Hu Guo-Hong , Wang Hui-Yun 
Published: May 2015

Abstract
Purpose: MicroRNA (miRNA) plays significant role in the development and progression of cancer. We aimed to identify miRNA signatures to be used as diagnostic and prognostic biomarkers in non-small-cell lung cancer (NSCLC).
Experimental Design: Patients with NSCLC who underwent surgical resection and didn't receive any therapy before surgery were randomly divided into training set (198 patients) and test set (199 patients). The miRNA expression levels were detected by microarray and selected miRNAs were verified by quantitative real-time PCR (qRT-PCR). The other 302 patients from another center were used as an independent set to verify the miRNA signature.
Results: A 37-miRNA signature consisting of 15 downregulated miRNAs and 22 upregulated miRNAs was established for distinguishing NSCLC specimens from noncancerous lung tissues in the training set with 98.2% accuracy. In the test set, the classification accuracy of the signature was 98.5%. Then three miRNAs were chosen to construct prognostic signature in the training set. A formula based on the 3 miRNAs was built to calculate prognostic index. Kaplan-Meier analysis showed that patients with a high prognostic index had a significant poorer survival than those with a low index. The 3-miRNA signature was validated in test set with the same formula for computing the prognostic index. The expression levels of 4 miRNAs including the 3 miRNA in the prognostic signature were verified by RT-PCR in 33 paired NSCLC and corresponding noncancerous lung tissues. The expression level of the 3 miRNA was detected by qRT-PCR in the independent set. Survival analysis showed that the 3-miRNA signature was associated with survival in the independent set. Multivariate analysis indicated that the 3-miRNA signature was an independent prognostic biomarker. A combination of the 3-miRNA signature and TNM stage had much better prognostic ability than did TNM stage alone in the training, test and independent sets.
Conclusions: The 37-miRNA and 3-miRNA signatures identified in our study may be useful biomarkers for diagnosis and prognosis of NSCLC patients.
Note: This abstract was not presented at the meeting.
Citation Format: Heng-Ying Pu, Da Fu, Mei-Yin Zhang, Yin-Lian Cha, Hai-Shan Peng, Lan-Jun Zhang, Wei-Hua Jia, Yi-Xin Zeng, Wan-Qing Liu, Steven X.F. Zheng, Guo-Hong Hu, Hui-Yun Wang. Prognostic value of microRNA signature in non-small-cell lung cancer: A microRNA expression analysis. [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 5223. doi:10.1158/1538-7445.AM2014-5223
Abstract 5225: MicroRNA profiling in serum samples from donors with germ cell cancer
Authors: Lee Kathy Y. , Patel Sunali , Hayashibara Kathleen , Chu Shirley , Gillis Ad J. M , Rijlaarsdam Martin , Dorssers Lambert C.J , Looijenga Leendert H. J 
Published: May 2015

Abstract
MicroRNAs are short non-coding RNA molecules (∼21 bases) that have been identified as important regulators of gene expression at the translational and transcriptional level. They are known to play a crucial role in cell development, differentiation, and disease. Dysregulation of miRNAs has been linked to cancer development and tumor progression. In addition, miRNAs have been identified as tumor classifiers and disease biomarkers. Recent studies have shown that miRNAs are present in body fluids (serum, saliva, semen, urine) thus providing a non-invasive tool to study and monitor disease states. Earlier research studies identified specific miRNAs as characteristic for germ cell tumors, such as testicular cancer (miR-372, miR-373). miRNA Profiling (∼760 miRNAs) was performed to identify additional miRNAs as candidate biomarkers in serum samples for testicular cancer (seminoma and non-seminoma types), from normal and cancer tissue in parallel with their matched serum samples collected from patients with testicular cancer. For this research study we used a miRNA specific bead capture system to isolate miRNAs from serum and TaqMan® Array Card platform for profiling. We will present results from this research study comparing the miRNA expression patterns in matched normal, cancer tissue, and serum.
For Research Use Only. Not for use in diagnostic procedures.
Citation Format: Kathy Y. Lee, Sunali Patel, Kathleen Hayashibara, Shirley Chu, Ad J. M Gillis, Martin Rijlaarsdam, Lambert C.J Dorssers, Leendert H. J Looijenga. MicroRNA profiling in serum samples from donors with germ cell 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 5225. doi:10.1158/1538-7445.AM2014-5225
Abstract 5227: The microRNA profile is altered in fibrosis-associated hepatocarcinogenesis in mice
Authors: Marrone April K. , Tryndyak Volodymyr , Chappell Grace , Beland Frederick A. , Rusyn Ivan , Pogribny Igor P. 
Published: May 2015

Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers and its incidence is rising worldwide. The molecular mechanisms associated with the development of HCC are complex and include multiple interconnected alterations driven by both genetic and epigenetic events. Mounting evidence indicates an important role of microRNAs (miRNAs), post-transcriptional negative regulators of gene expression, in the pathogenesis of HCC. In humans, the development of HCC is commonly associated with liver cirrhosis. To mimic the molecular pathogenesis of human HCC, we used a mouse model of fibrosis-associated liver cancer, which was designed to emulate cirrhotic liver. Tumor and non-tumor liver samples from B6C3F1 mice treated with N-nitrosodiethylamine (DEN; a single ip injection of 1 mg/kg at 14 days of age) and carbon tetrachloride (CCl4; 200 µl/kg, 2 times/week ip for 14 weeks starting at 8 weeks of age) were analyzed. Using TaqMan® array miRNA cards, we identified a total of 52 and 45 miRNAs that were differentially expressed in tumor and non-tumor liver tissue, respectively, from DEN/CCl4-treated mice as compared to those in livers of vehicle-treated control B6C3F1 mice. Importantly, 27 differentially expressed miRNAs were common for both tumor and non-tumor samples from DEN/CCl4-treated mice. These miRNAs are involved in the major cancer pathways including apoptosis, cell proliferation, angiogenesis, and epithelial-to-mesenchymal transition. These results suggest that changes in miRNA expression during hepatocarcinogenesis may occur at very early stages of the carcinogenic process, preceding the formation of detectable neoplastic lesions. Most notably, our results showing 27 miRNAs common for tumor and non-tumor tissue suggest that a miRNA profile associated with the development of HCC could potentially be used to decipher the precise molecular mechanisms of disease progression and/or be used as early markers for detecting neoplastic lesions in the liver.
Citation Format: April K. Marrone, Volodymyr Tryndyak, Grace Chappell, Frederick A. Beland, Ivan Rusyn, Igor P. Pogribny. The microRNA profile is altered in fibrosis-associated hepatocarcinogenesis in mice. [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 5227. doi:10.1158/1538-7445.AM2014-5227