http://hdl.handle.net/10027/7231 Wed, 19 Jun 2013 00:28:30 GMT 2013-06-19T00:28:30Z http://hdl.handle.net/10027/8400 Bioinformatic resources of microRNA sequences, gene targets, and genetic variation Mu, Wenbo; Zhang, Wei Variation in quantitative gene expression has been observed in natural populations and associated with various complex traits/phenotypes such as risks for common diseases and drug response. MicroRNAs (miRNAs), a family of small, non-coding RNA molecules, have been demonstrated to be an important class of gene regulators that mostly downregulate gene expression at the post-transcriptional level. A comprehensive and reliable catalogue of miRNAs and miRNA gene targets is critical to understanding the gene regulatory networks.Though experimental approaches have been used to identify many miRNAs and their gene targets, due to cost and efficiency, currently miRNA and target identification still largely relies on computational algorithms. We reviewed several widely used bioinformatic resources of miRNA sequences and gene targets that take advantage of the unique characteristics of miRNA–mRNA interactions, experimental validation, as well as the integration of sequence-based evidence and microarray expression data. Furthermore, given the importance of miRNAs in regulating gene expression, elucidating expression quantitative trait loci involved with miRSNPs or miR-polymorphisms will help improve our understanding of complex traits.We reviewed the available resources of miRNA genetic variation, and the current progress (e.g., the 1000 Genomes Project) in detailing the genetic variation in miRNA-related single nucleotide polymorphisms (SNPs).We also provided our perspectives of the potential impact of next-generation sequencing on the research of miRNAs, gene targets, and miRSNPs. These bioinformatic resources may help interpret experimental and association study results, thus enhancing our knowledge of the dynamic gene regulatory networks and the physiological pathways for complex traits/phenotypes. Prospectively, these bioinformatic resources of miRNAs will need to address the challenges raised by the application of next-generation sequencing in miRNA research. Copyright: © 2012 Mu and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited. This Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permission. doi: 10.3389/fgene.2012.00031 Sun, 01 Jan 2012 06:00:00 GMT http://hdl.handle.net/10027/8400 2012-01-01T06:00:00Z http://hdl.handle.net/10027/8190 Carnosol: A Promising Anti-Cancer and Anti-Inflammatory Agent Johnson, Jeremy J. The Mediterranean diet and more specifically certain meats, fruits, vegetables, and olive oil found in certain parts of the Mediterranean region have been associated with a decreased cardiovascular and diabetes risk. More recently, several population based studies have observed with these lifestyle choices have reported an overall reduced risk for several cancers. One study in particular observed an inverse relationship between consumption of Mediterranean herbs such as rosemary, sage, parsley, and oregano with lung cancer. In light of these findings there is a need to explore and identify the anti-cancer properties of these medicinal herbs and to identify the phytochemicals therein. One agent in particular, carnosol, has been evaluated for anti-cancer property in prostate, breast, skin, leukemia, and colon cancer with promising results. These studies have provided evidence that carnosol targets multiple deregulated pathways associated with inflammation and cancer that include nuclear factor kappa B (NFκB), apoptotic related proteins, phosphatidylinositol-3-kinase (PI3 K)/Akt, androgen and estrogen receptors, as well as molecular targets. In addition, carnosol appears to be well tolerated in that it has a selective toxicity towards cancer cells versus non-tumorigenic cells and is well tolerated when administered to animals. This mini-review reports on the pre-clinical studies that have been performed to date with carnosol describing mechanistic, efficacy, and safety/tolerability studies as a cancer chemoprevention and anti-cancer agent. NOTICE: this is the author’s version of a work that was accepted for publication in Cancer Letters. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Cancer Letters, Vol 305, Issue 1, June 1, 2011. DOI: 10.1016/j.canlet.2011.02.005. The original publication is available at www.elsevier.com. Wed, 01 Jun 2011 05:00:00 GMT http://hdl.handle.net/10027/8190 2011-06-01T05:00:00Z http://hdl.handle.net/10027/7619 Deregulation of manganese superoxide dismutase (SOD2) expression and lymph node metastasis in tongue squamous cell carcinoma Liu, Xiqiang; Wang, Anxun; Muzio, Lorenzo L.; Kolokythas, Antonia; Sheng, Shihu; Rubini, Corrado; Ye, Hui; Shi, Fei; Yu, Tianwei; Crowe, David L.; Zhou, Xiofeng Background: Lymph node metastasis is a critical event in the progression of tongue squamous cell carcinoma (TSCC). The identification of biomarkers associated with the metastatic process would provide critical prognostic information to facilitate clinical decision making. Previous studies showed that deregulation of manganese superoxide dismutase (SOD2) expression is a frequent event in TSCC and may be associated with enhanced cell invasion. The purpose of this study is to further evaluate whether the expression level of SOD2 is correlated with the metastatic status in TSCC patients. Methods: We first examined the SOD2 expression at mRNA level on 53 TSCC and 22 normal control samples based on pooled-analysis of existing microarray datasets. To confirm our observations, we examined the expression of SOD2 at protein level on an additional TSCC patient cohort (n = 100), as well as 31 premalignant dysplasias, 15 normal tongue mucosa, and 32 lymph node metastatic diseases by immunohistochemistry (IHC). Results: The SOD2 mRNA level in primary TSCC tissue is reversely correlated with lymph node metastasis in the first TSCC patient cohort. The SOD2 protein level in primary TSCC tissue is also reversely correlated with lymph node metastasis in the second TSCC patient cohort. Deregulation of SOD2 expression is a common event in TSCC and appears to be associated with disease progression. Statistical analysis revealed that the reduced SOD2 expression in primary tumor tissue is associated with lymph node metastasis in both TSCC patient cohorts examined. Conclusions: Our study suggested that the deregulation of SOD2 in TSCC has potential predictive values for lymph node metastasis, and may serve as a therapeutic target for patients at risk of metastasis. The original version is available through BioMed Central at DOI: 10.1186/1471-2407-10-365. © 2010 Liu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Fri, 09 Jul 2010 05:00:00 GMT http://hdl.handle.net/10027/7619 2010-07-09T05:00:00Z http://hdl.handle.net/10027/7605 Steroid receptor coactivator 1 deficiency increases MMTV-neu mediated tumor latency and differentiation specific gene expression, decreases metastasis, and inhibits response to PPAR ligands Han, Ji S. Background: The peroxisome proliferator activated receptor (PPAR) subgroup of the nuclear hormone receptor superfamily is activated by a variety of natural and synthetic ligands. PPARs can heterodimerize with retinoid X receptors, which have homology to other members of the nuclear receptor superfamily. Ligand binding to PPAR/RXRs results in recruitment of transcriptional coactivator proteins such as steroid receptor coactivator 1 (SRC-1) and CREB binding protein (CBP). Both SRC-1 and CBP are histone acetyltransferases, which by modifying nucleosomal histones, produce more open chromatin structure and increase transcriptional activity. Nuclear hormone receptors can recruit limiting amounts of coactivators from other transcription factor binding sites such as AP-1, thereby inhibiting the activity of AP-1 target genes. PPAR and RXR ligands have been used in experimental breast cancer therapy. The role of coactivator expression in mammary tumorigenesis and response to drug therapy has been the subject of recent studies. Methods: We examined the effects of loss of SRC-1 on MMTV-neu mediated mammary tumorigenesis. Results: SRC-1 null mutation in mammary tumor prone mice increased the tumor latency period, reduced tumor proliferation index and metastasis, inhibited response to PPAR and RXR ligands, and induced genes involved in mammary gland differentiation. We also examined human breast cancer cell lines overexpressing SRC-1 or CBP. Coactivator overexpression increased cellular proliferation with resistance to PPAR and RXR ligands and remodeled chromatin of the proximal epidermal growth factor receptor promoter. Conclusions: These results indicate that histone acetyltransferases play key roles in mammary tumorigenesis and response to anti-proliferative therapies. The definitive version is available through BioMed Central at DOI: 10.1186/1471-2407-10-629. © 2010 Han and Crowe; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Tue, 16 Nov 2010 06:00:00 GMT http://hdl.handle.net/10027/7605 2010-11-16T06:00:00Z