title: MicroRNA-21 regulates prostaglandin E2 signaling pathway by targeting 15-hydroxyprostaglandin dehydrogenase in tongue squamous cell carcinoma.
abstract: Oral tongue squamous cell carcinoma (OTSCC) is one of the most aggressive forms of head and neck/oral cancer (HNOC), and is a complex disease with extensive genetic and epigenetic defects, including microRNA deregulation. Identifying the deregulation of microRNA-mRNA regulatory modules (MRMs) is crucial for understanding the role of microRNA in OTSCC.
  
  
  
  A comprehensive bioinformatics analysis was performed to identify MRMs in HNOC by examining the correlation among differentially expressed microRNA and mRNA profiling datasets and integrating with 12 different sequence-based microRNA target prediction algorithms. Confirmation experiments were performed to further assess the correlation among MRMs using OTSCC patient samples and HNOC cell lines. Functional analyses were performed to validate one of the identified MRMs: miR-21-15-Hydroxyprostaglandin Dehydrogenase (HPGD) regulatory module.
  
  
  
  Our bioinformatics analysis revealed 53 MRMs that are deregulated in HNOC. Four high confidence MRMs were further defined by confirmation experiments using OTSCC patient samples and HNOC cell lines, including miR-21-HPGD regulatory module. HPGD is a known anti-tumorigenic effecter, and it regulates the tumorigenic actions of Prostaglandin E2 (PGE2) by converts PGE2 to its biologically inactive metabolite. Ectopic transfection of miR-21 reduced the expression of HPGD in OTSCC cell lines, and the direct targeting of the miR-21 to the HPGD mRNA was confirmed using a luciferase reporter gene assay. The PGE2-mediated upregulation of miR-21 was also confirmed which suggested the existence of a positive feed-forward loop that involves miR-21, HPGD and PGE2 in OTSCC cells that contribute to tumorigenesis.
  
  
  
  We identified a number of high-confidence MRMs in OTSCC, including miR-21-HPGD regulatory module, which may play an important role in the miR-21-HPGD-PGE2 feed-forward loop that contributes to tumorigenesis.
authors: Center for Molecular Biology of Oral Diseases, Department of Periodontics, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA.|Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Qianting
authors: Q
authors: He
authors: Center for Molecular Biology of Oral Diseases, Department of Periodontics, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA.
authors: Zujian
authors: Z
authors: Chen
authors: Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Qian
authors: Q
authors: Dong
authors: Center for Molecular Biology of Oral Diseases, Department of Periodontics, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA.|Department of Oral and Maxillofacial Surgery, Nan Fang Hospital, Southern Medical University, Guangzhou, China.
authors: Leitao
authors: L
authors: Zhang
authors: Center for Molecular Biology of Oral Diseases, Department of Periodontics, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA.|Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors: Dan
authors: D
authors: Chen
authors: Center for Molecular Biology of Oral Diseases, Department of Periodontics, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA.
authors: Aditi
authors: A
authors: Patel
authors: Center for Molecular Biology of Oral Diseases, Department of Periodontics, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA.
authors: Ajay
authors: A
authors: Koya
authors: Department of Oral Biology, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA.
authors: Xianghong
authors: X
authors: Luan
authors: Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
authors: Robert J
authors: RJ
authors: Cabay
authors: Department of Bioengineering, College of Engineering, University of Illinois at Chicago, Chicago, IL, USA.|UIC Cancer Center, Graduate College, University of Illinois at Chicago, Chicago, IL, USA.
authors: Yang
authors: Y
authors: Dai
authors: Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. anxunwang@yahoo.com.
authors: Anxun
authors: A
authors: Wang
authors: Center for Molecular Biology of Oral Diseases, Department of Periodontics, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA. xfzhou@uic.edu.|UIC Cancer Center, Graduate College, University of Illinois at Chicago, Chicago, IL, USA. xfzhou@uic.edu.|Guanghua School and Research Institute of Stomatology, Sun Yat-sen University, Guangzhou, China. xfzhou@uic.edu.
authors: Xiaofeng
authors: X
authors: Zhou
mesh_terms: D020029:Base Pairing; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D015232:Dinoprostone / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D014062:Tongue Neoplasms / Q000235:genetics* / Q000378:metabolism*
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D015232:Dinoprostone
keywords: HPGD; PGE2; miR-21; microRNA; microRNA-mRNA regulatory module