Identification of a Long Non-Coding RNA As a Novel Biomarker and Potential Therapeutic Target for Metastatic Prostate Cancer
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Long Noncoding RNA and Cancer: a New Paradigm Arunoday Bhan, Milad Soleimani, and Subhrangsu S
Published OnlineFirst July 12, 2017; DOI: 10.1158/0008-5472.CAN-16-2634 Cancer Review Research Long Noncoding RNA and Cancer: A New Paradigm Arunoday Bhan, Milad Soleimani, and Subhrangsu S. Mandal Abstract In addition to mutations or aberrant expression in the moting (oncogenic) functions. Because of their genome-wide protein-coding genes, mutations and misregulation of noncod- expression patterns in a variety of tissues and their tissue- ing RNAs, in particular long noncoding RNAs (lncRNA), appear specific expression characteristics, lncRNAs hold strong prom- to play major roles in cancer. Genome-wide association studies ise as novel biomarkers and therapeutic targets for cancer. In of tumor samples have identified a large number of lncRNAs this article, we have reviewed the emerging functions and associated with various types of cancer. Alterations in lncRNA association of lncRNAs in different types of cancer and dis- expression and their mutations promote tumorigenesis and cussed their potential implications in cancer diagnosis and metastasis. LncRNAs may exhibit tumor-suppressive and -pro- therapy. Cancer Res; 77(15); 1–17. Ó2017 AACR. Introduction lncRNAs (lincRNA) originate from the region between two pro- tein-coding genes; enhancer lncRNAs (elncRNA) originate from Cancer is a complex disease associated with a variety of genetic the promoter enhancer regions; bidirectional lncRNAs are local- mutations, epigenetic alterations, chromosomal translocations, ized within the vicinity of a coding transcript of the opposite deletions, and amplification (1). Noncoding RNAs (ncRNA) are strand; sense-overlapping lncRNAs overlap with one or more an emerging class of transcripts that are coded by the genome but introns and exons of different protein-coding genes in the sense are mostly not translated into proteins (2). -
Database Tool Pseudomap: an Innovative and Comprehensive Resource for Identification of Sirna-Mediated Mechanisms in Human Trans
Database, Vol. 2013, Article ID bat001, doi:10.1093/database/bat001 ............................................................................................................................................................................................................................................................................................. Database tool pseudoMap: an innovative and comprehensive resource for identification of siRNA-mediated mechanisms in human Downloaded from transcribed pseudogenes Wen-Ling Chan1,2, Wen-Kuang Yang3,4, Hsien-Da Huang1,2,* and Jan-Gowth Chang5,6,7,* http://database.oxfordjournals.org/ 1Institute of Bioinformatics and Systems Biology, 2Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, 3Cell/Gene Therapy Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, 4Departments of Biochemistry and Medicine, China Medical University, Taichung, 5Center of RNA Biology and Clinical Application, 6Department of Laboratory Medicine, China Medical University Hospital, Taichung, and 7School of Medicine, China Medical University, Taichung, Taiwan *Corresponding author: Tel: +886 4 22052121 ext. 2008; Email: [email protected]; Fax: +886 4 22031029 Correspondence may also be addressed to Hsien-Da Huang, Tel: +886 3 5712121 ext. 56957; Email: [email protected]; Fax: +886 3 5739320 Submitted 31 October 2012; Revised 1 January 2013; Accepted 3 January 2013 Citation details: Chan,W.-L., Yang,W.-K., Huang,H.-D. et al. pseudoMap: -
(12) United States Patent (10) Patent No.: US 7,807,373 B2 Srivastava Et Al
US007807373B2 (12) United States Patent (10) Patent No.: US 7,807,373 B2 Srivastava et al. (45) Date of Patent: Oct. 5, 2010 (54) PROSTATE SPECIFIC GENE, PCGEM1, AND GenBank. Accession No. ACO 13401, GI:8569780, 169700 bp DNA, METHODS OF USING PCEGM1 TO DETECT, Jul. 7, 2000. TREAT, AND PREVENT PROSTATE CANCER “AC003046.” EBI Database XPO02143197, Dec. 1, 2001. (75) Inventors: Shiv Srivastava, Potomac, MD (US); Srikantanet al., “Structure and Expression of a Novel Prostate Spe Judd W. Moul, Bethesda, MD (US); cific Gene: PCGEM1. Proc. American Assoc. Cancer Research Vasantha Srikantan, Rockville, MD Annual, XP000929230, vol. 40, p. 37 (Mar. 1999). (US); Zhiqiang Zou, Gaithersburg, MD Bussemakers et al., “A New Prostate-Specific Arker, Strongly (US) Overexpressed in Prostatic Tumors.” Urological Research, XP0020743.05, vol. 25, No. 1, p. 76 (Feb. 1997). (73) Assignee: Henry M. Jackson Foundation for the Wang et al., “Genes Regulated by Androgen in the Rat Ventral Pros Advancement of Military Medicine, tate.” Proc. Nat.1 Acad. Sci., U.S.A., vol. 94, pp. 12999-13004 (Nov. Rockville, MD (US) 1997). “ACO 13401, EBI Database XP002143200, Apr. 16, 2005. (*) Notice: Subject to any disclaimer, the term of this Srikantan et al., “PCGEM1, a Prostate-Specific Gene, Is Overex patent is extended or adjusted under 35 posed in Prostate Cancer.” Proc. Natl. Acad. Sci., vol.97, No. 22, pp. U.S.C. 154(b) by 285 days. 12216-12221 (Oct. 24, 2000). (21) Appl. No.: 12/166,723 Srikantan et al., Identification of Prostate Cancer Associated Novel Gene Expression Alterations, Proc. American Assoc. Cancer (22) Filed: Jul. -
Oncotarget-05-764.Pdf
Open Research Online The Open University’s repository of research publications and other research outputs Identification of a long non-coding RNA as a novel biomarker and potential therapeutic target for metastatic prostate cancer Journal Item How to cite: Crea, Francesco; Watahiki, Akira; Quagliata, Luca; Xue, Hui; Pikor, Larissa; Parolia, Abhijit; Wang, Yuwei; Lin, Dong; Lam, Wan L.; Farrar, William L.; Isogai, Takao; Morant, Rudolf; Castori-Eppenberger, Serenella; Chi, Kim N.; Wang, Yuzhuo and Helgason, Cheryl D. (2014). Identification of a long non-coding RNA as a novel biomarker and potential therapeutic target for metastatic prostate cancer. Oncotarget, 5(3) pp. 764–774. For guidance on citations see FAQs. c 2014 The Authors https://creativecommons.org/licenses/by/4.0/ Version: Version of Record Link(s) to article on publisher’s website: http://dx.doi.org/doi:10.18632/oncotarget.1769 Copyright and Moral Rights for the articles on this site are retained by the individual authors and/or other copyright owners. For more information on Open Research Online’s data policy on reuse of materials please consult the policies page. oro.open.ac.uk www.impactjournals.com/oncotarget/ Oncotarget, Vol. 5, No. 3 Identification of a long non-coding RNA as a novel biomarker and potential therapeutic target for metastatic prostate cancer Francesco Crea1, Akira Watahiki1,2, Luca Quagliata3, Hui Xue1, Larissa Pikor4, Abhijit Parolia1,5, Yuwei Wang1, Dong Lin1,2, Wan L. Lam4, William L. Farrar6, Takao Isogai7, Rudolf Morant8, Serenella Castori-Eppenberger3, Kim N. Chi2,9, Yuzhuo Wang1,2, and Cheryl D. Helgason1 1 Experimental Therapeutics, BC Cancer Agency Cancer Research Centre, Vancouver BC, Canada. -
Disruption of YY1-EZH2 Interaction Using Synthetic Peptides Inhibits Breast Cancer Development
cancers Article Disruption of YY1-EZH2 Interaction Using Synthetic Peptides Inhibits Breast Cancer Development Cheng Yi 1, Guangyue Li 1, Wenmeng Wang 1, Yixuan Sun 1, Yueling Zhang 2, Chen Zhong 3, Daniel B. Stovall 4, Dangdang Li 1, Jinming Shi 1,* and Guangchao Sui 1,* 1 Key Laboratory of Saline-Alkali Vegetation Ecology Restoration, Ministry of Education, College of Life Science, Northeast Forestry University, Harbin 150040, China; [email protected] (C.Y.); [email protected] (G.L.); [email protected] (W.W.); [email protected] (Y.S.); [email protected] (D.L.) 2 State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China; [email protected] 3 State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China; [email protected] 4 College of Arts and Sciences, Winthrop University, Rock Hill, SC 29733, USA; [email protected] * Correspondence: [email protected] (J.S.); [email protected] (G.S.); Tel.: +86-451-82191081 (J.S. & G.S.) Simple Summary: Both Yin Yang 1 (YY1) and enhancer of zeste homolog 2 (EZH2) are oncogenes with overexpressed statuses in cancers. As a transcription factor, YY1 recruits EZH2 through its oncoprotein binding (OPB) domain to repress gene expression. In this study, we identified the interaction domain of YY1 on EZH2 protein with amino acids 493–519, named the YY1 protein binding (YPB) domain. Synthetic peptides using YPB and OPB domain sequences effectively blocked endogenous YY1-EZH2 interaction. Functionally, YPB and OPB peptides could efficiently inhibit the Citation: Yi, C.; Li, G.; Wang, W.; proliferation of breast cancer cells, promote their apoptosis, and reduce tumor growth in a xenograft Sun, Y.; Zhang, Y.; Zhong, C.; Stovall, mouse model. -
Novel Long Non-Coding Rnas Are Specific Diagnostic and Prognostic Markers for Prostate Cancer
www.impactjournals.com/oncotarget/ Oncotarget, Vol. 6, No.6 Novel long non-coding RNAs are specific diagnostic and prognostic markers for prostate cancer René Böttcher1,3, A. Marije Hoogland2, Natasja Dits1, Esther I. Verhoef2, Charlotte Kweldam2, Piotr Waranecki1, Chris H. Bangma1, Geert J.L.H. van Leenders2, Guido Jenster1 1Dept. of Urology, Erasmus MC, Rotterdam, The Netherlands 2Dept. of Pathology, Erasmus MC, Rotterdam, The Netherlands 3Dept. of Bioinformatics, Technical University of Applied Sciences Wildau, Wildau, Germany Correspondence to: Guido Jenster, e-mail: [email protected] Keywords: Long non-coding RNA, prostate cancer, in situ hybridization, exon array, biomarkers Received: August 22, 2014 Accepted: December 08, 2014 Published: February 17, 2015 ABSTRACT Current prostate cancer (PCa) biomarkers such as PSA are not optimal in distinguishing cancer from benign prostate diseases and predicting disease outcome. To discover additional biomarkers, we investigated PCa-specific expression of novel unannotated transcripts. Using the unique probe design of Affymetrix Human Exon Arrays, we identified 334 candidates (EPCATs), of which 15 were validated by RT-PCR. Combined into a diagnostic panel, 11 EPCATs classified 80% of PCa samples correctly, while maintaining 100% specificity. High specificity was confirmed by in situ hybridization for EPCAT4R966 and EPCAT2F176 (SChLAP1) on extensive tissue microarrays. Besides being diagnostic, EPCAT2F176 and EPCAT4R966 showed significant association with pT-stage and were present in PIN lesions. We also found EPCAT2F176 and EPCAT2R709 to be associated with development of metastases and PCa-related death, and EPCAT2F176 to be enriched in lymph node metastases. Functional significance of expression of 9 EPCATs was investigated by siRNA transfection, revealing that knockdown of 5 different EPCATs impaired growth of LNCaP and 22RV1 PCa cells. -
Microrna-Mediated Networks Underlie Immune Response Regulation in Papillary Thyroid 51
OPEN MicroRNA-mediated networks underlie SUBJECT AREAS: immune response regulation in papillary GENE REGULATORY NETWORKS thyroid carcinoma CANCER GENOMICS Chen-Tsung Huang1, Yen-Jen Oyang1, Hsuan-Cheng Huang4 & Hsueh-Fen Juan1,2,3 Received 1 2 15 July 2014 Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan, Department of Life Science, National Taiwan University, Taipei, Taiwan, 3Institute of Molecular and Cellular Biology, National Taiwan University, Accepted Taipei, Taiwan, 4Institute of Biomedical Informatics and Center for Systems and Synthetic Biology, National Yang-Ming University, 9 September 2014 Taipei, Taiwan. Published 29 September 2014 Papillary thyroid carcinoma (PTC) is a common endocrine malignancy with low death rate but increased incidence and recurrence in recent years. MicroRNAs (miRNAs) are small non-coding RNAs with diverse regulatory capacities in eukaryotes and have been frequently implied in human cancer. Despite current Correspondence and progress, however, a panoramic overview concerning miRNA regulatory networks in PTC is still lacking. requests for materials Here, we analyzed the expression datasets of PTC from The Cancer Genome Atlas (TCGA) Data Portal and demonstrate for the first time that immune responses are significantly enriched and under specific should be addressed to regulation in the direct miRNA2target network among distinctive PTC variants to different extents. H.C.H. (hsuancheng@ Additionally, considering the unconventional properties of miRNAs, we explore the protein-coding ym.edu.tw) or H.F.J. competing endogenous RNA (ceRNA) and the modulatory networks in PTC and unexpectedly disclose ([email protected]) concerted regulation of immune responses from these networks. Interestingly, miRNAs from these conventional and unconventional networks share general similarities and differences but tend to be disparate as regulatory activities increase, coordinately tuning the immune responses that in part account for PTC tumor biology. -
Detailed Characterization of Human Induced Pluripotent Stem Cells Manufactured for Therapeutic Applications
Stem Cell Rev and Rep DOI 10.1007/s12015-016-9662-8 Detailed Characterization of Human Induced Pluripotent Stem Cells Manufactured for Therapeutic Applications Behnam Ahmadian Baghbaderani 1 & Adhikarla Syama2 & Renuka Sivapatham3 & Ying Pei4 & Odity Mukherjee2 & Thomas Fellner1 & Xianmin Zeng3,4 & Mahendra S. Rao5,6 # The Author(s) 2016. This article is published with open access at Springerlink.com Abstract We have recently described manufacturing of hu- help determine which set of tests will be most useful in mon- man induced pluripotent stem cells (iPSC) master cell banks itoring the cells and establishing criteria for discarding a line. (MCB) generated by a clinically compliant process using cord blood as a starting material (Baghbaderani et al. in Stem Cell Keywords Induced pluripotent stem cells . Embryonic stem Reports, 5(4), 647–659, 2015). In this manuscript, we de- cells . Manufacturing . cGMP . Consent . Markers scribe the detailed characterization of the two iPSC clones generated using this process, including whole genome se- quencing (WGS), microarray, and comparative genomic hy- Introduction bridization (aCGH) single nucleotide polymorphism (SNP) analysis. We compare their profiles with a proposed calibra- Induced pluripotent stem cells (iPSCs) are akin to embryonic tion material and with a reporter subclone and lines made by a stem cells (ESC) [2] in their developmental potential, but dif- similar process from different donors. We believe that iPSCs fer from ESC in the starting cell used and the requirement of a are likely to be used to make multiple clinical products. We set of proteins to induce pluripotency [3]. Although function- further believe that the lines used as input material will be used ally identical, iPSCs may differ from ESC in subtle ways, at different sites and, given their immortal status, will be used including in their epigenetic profile, exposure to the environ- for many years or even decades. -
Database Tool Pseudomap: an Innovative and Comprehensive Resource for Identification of Sirna-Mediated Mechanisms in Human Transcribed Pseudogenes
Database, Vol. 2013, Article ID bat001, doi:10.1093/database/bat001 ............................................................................................................................................................................................................................................................................................. Database tool pseudoMap: an innovative and comprehensive resource for identification of siRNA-mediated mechanisms in human transcribed pseudogenes Wen-Ling Chan1,2, Wen-Kuang Yang3,4, Hsien-Da Huang1,2,* and Jan-Gowth Chang5,6,7,* 1Institute of Bioinformatics and Systems Biology, 2Department of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, 3Cell/Gene Therapy Research Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, 4Departments of Biochemistry and Medicine, China Medical University, Taichung, 5Center of RNA Biology and Clinical Application, 6Department of Laboratory Medicine, China Medical University Hospital, Taichung, and 7School of Medicine, China Medical University, Taichung, Taiwan *Corresponding author: Tel: +886 4 22052121 ext. 2008; Email: [email protected]; Fax: +886 4 22031029 Correspondence may also be addressed to Hsien-Da Huang, Tel: +886 3 5712121 ext. 56957; Email: [email protected]; Fax: +886 3 5739320 Submitted 31 October 2012; Revised 1 January 2013; Accepted 3 January 2013 Citation details: Chan,W.-L., Yang,W.-K., Huang,H.-D. et al. pseudoMap: an innovative and comprehensive resource for identification -
The Emergence of Lncrnas in Cancer Biology
Review The Emergence of lncRNAs in Cancer Biology John R. Prensner1,2 and Arul M. Chinnaiyan1–5 AbstAt R c The discovery of numerous noncoding RNA (ncRNA) transcripts in species from yeast to mammals has dramatically altered our understanding of cell biology, especially the biology of diseases such as cancer. In humans, the identification of abundant long ncRNA (lncRNA) >200 bp has catalyzed their characterization as critical components of cancer biology. Recently, roles for lncRNAs as drivers of tumor suppressive and oncogenic functions have appeared in prevalent cancer types, such as breast and prostate cancer. In this review, we highlight the emerging impact of ncRNAs in cancer research, with a particular focus on the mechanisms and functions of lncRNAs. Significance: lncRNAs represent the leading edge of cancer research. Their identity, function, and dysregulation in cancer are only beginning to be understood, and recent data suggest that they may serve as master drivers of carcinogenesis. Increased research on these RNAs will lead to a greater un- derstanding of cancer cell function and may lead to novel clinical applications in oncology. Cancer Discovery; 1(5):391–407. ©2011 AACR. intRoduction transcription reflects true biology or by-products of a leaky transcriptional system. Encompassed within these studies are A central question in biology has been, Which regions of the broad questions of what constitutes a human gene, what the human genome constitute its functional elements: those distinguishes a gene from a region that is simply transcribed, expressed as genes or those serving as regulatory elements? and how we interpret the biologic meaning of transcription. -
PCGEM1, a Prostate-Specific Gene, Is Overexpressed in Prostate Cancer
PCGEM1, a prostate-specific gene, is overexpressed in prostate cancer Vasantha Srikantan*†, Zhiqiang Zou*†, Gyorgy Petrovics*, Linda Xu*, Meena Augustus*‡, Leland Davis*, Jeffrey R. Livezey*, Theresa Connell*, Isabell A. Sesterhenn§, Kiyoshi Yoshino¶, Gregory S. Buzard¶, F. K. Mostofi§, David G. McLeod*ሻ, Judd W. Moul*ሻ, and Shiv Srivastava*,** *Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799; ‡Genetics Department, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4470; §Armed Forces Institute of Pathology, Department of Genitourinary Pathology, Washington, DC 20307; ¶Laboratory of Comparative Carcinogenesis, Science Applications International Corporation, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD 21702-1201; and Urology Service, Department of Surgery, Walter Reed Army Medical Center, Washington, DC 20307-5001 Communicated by Bernhard Witkop, National Institutes of Health, Chevy Chase, MD, August 17, 2000 (received for review February 28, 2000) A prostate-specific gene, PCGEM1, was identified by differential anti-PSMA monoclonal antibodies (4). Furthermore, promising display analysis of paired normal and prostate cancer tissues. immunotherapy approaches are being pursued with PSMA Multiple tissue Northern blot analysis revealed that PCGEM1 was peptides (5). Recently described prostate-specific genes include expressed exclusively in human prostate tissue. Analysis of PC- an androgen-regulated homeobox gene, NKX3.1, which exhibits GEM1 expression in matched normal and primary tumor specimens function(s) in mouse prostate growth͞development (6, 7) and revealed tumor-associated overexpression in 84% of patients with shows overexpression in a subset of CaP (26). A prostate-specific prostate cancer by in situ hybridization assay and in 56% of gene, prostate stem cell antigen, has been shown to exhibit patients by reverse transcription–PCR assay. -
Lncrna‑P21 Promotes Chondrocyte Apoptosis in Osteoarthritis by Acting As a Sponge for Mir‑451
MOLECULAR MEDICINE REPORTS 18: 5295-5301, 2018 LncRNA‑p21 promotes chondrocyte apoptosis in osteoarthritis by acting as a sponge for miR‑451 LUPING TANG, JIANBO DING, GUANGJU ZHOU and ZHIHAI LIU Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China Received December 20, 2017; Accepted September 11, 2018 DOI: 10.3892/mmr.2018.9506 Abstract. Osteoarthritis (OA) is the most common type of by the overexpression of lncRNA-p21 was abolished by the arthritis, and remains to be social and medical challenge. miR-451 mimic. Investigation into the underlying mechanism Thus, identifying novel molecular targets is important for revealed that lncRNA-p21 interacted with miRNA-451. In the prevention and treatment of OA. Long noncoding RNAs addition, lncRNA-p21 negatively regulated the expression of (lncRNAs) have been reported to modulate various biological miR-451. Furthermore, lncRNA-p21 promoted the apoptosis and pathological processes. The aim of the present study was of chondrocytes in OA by acting as a sponge for miR-451. to investigate the role of lncRNA-p21 in OA and its underlying Thus, lncRNA-p21 was proposed as a promising target for the mechanism, in order to better understand the development of OA treatment of OA. and its treatment. Chondrocytes were isolated from cartilage samples obtained from OA and normal patients. Chondrocytes Introduction were transfected with microRNA (miRNA/miR)-451 mimics, miR-451 inhibitor, pcDNA3.1(+)-p21 or small interfering Osteoarthritis (OA) is reported to afflict nearly 250 million RNA-p21. Flow cytometry was performed to analyze cell people in the whole world and is the most common apoptosis and reverse transcription-quantitative polymerase arthritis (1,2).