caa a22 4500 445861894 CHVBK 20180317145446.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s00439-010-0915-3 doi (NATIONALLICENCE)springer-10.1007/s00439-010-0915-3 Identification and experimental validation of G protein alpha inhibiting activity polypeptide 2 (GNAI2) as a microRNA-138 target in tongue squamous cell carcinoma [Elektronische Daten] [Lu Jiang, Yang Dai, Xiqiang Liu, Cheng Wang, Anxun Wang, Zujian Chen, Caroline Heidbreder, Antonia Kolokythas, Xiaofeng Zhou] MicroRNA deregulation is a critical event in tumor initiation and progression. The down-regulation of microRNA-138 has been frequently observed in various cancers, including tongue squamous cell carcinoma (TSCC). Our previous studies suggest that deregulation of miR-138 is associated with the enhanced proliferation and invasion in TSCC cells. Here, we seek to identify the targets of miR-138 in TSCC, and explore their functional relevance in tumorigenesis. Our genome-wide expression profiling experiments identified a panel of 194 unique transcripts that were significantly down-regulated in TSCC cells transfected with miR-138. A comprehensive screening using six different sequence-based microRNA target prediction algorithms revealed that 51 out of these 194 down-regulated transcripts are potential direct targets for miR-138. These targets include: chloride channel, nucleotide-sensitive, 1A (CLNS1A), G protein alpha inhibiting activity polypeptide 2 (GNAI2), solute carrier family 20, member 1 (SLC20A1), eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1), and Rho-related GTP-binding protein C (RhoC). GNAI2 is a known proto-oncogene that is involved in the initiation and progression of several different types of tumors. Direct targeting of miR-138 to two candidate binding sequences located in the 3′-untranslated region of GNAI2 mRNA was confirmed using luciferase reporter gene assays. Knockdown of miR-138 in TSCC cells enhanced the expression of GNAI2 at both mRNA and protein levels. In contrast, ectopic transfection of miR-138 reduced the expression of GNAI2, which, in consequence, led to reduced proliferation, cell cycle arrest and apoptosis. In summary, we identified a number of high-confident miR-138 target genes, including proto-oncogene GNAI2, which may play an important role in TSCC initiation and progression. Springer-Verlag, 2010 Jiang Lu Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Room 530C, 60612, Chicago, IL, USA aut Dai Yang Department of Bioengineering, College of Engineering, University of Illinois at Chicago, Chicago, IL, USA aut Liu Xiqiang Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Room 530C, 60612, Chicago, IL, USA aut Wang Cheng Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Room 530C, 60612, Chicago, IL, USA aut Wang Anxun Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Room 530C, 60612, Chicago, IL, USA aut Chen Zujian Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Room 530C, 60612, Chicago, IL, USA aut Heidbreder Caroline Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Room 530C, 60612, Chicago, IL, USA aut Kolokythas Antonia Department of Oral and Maxillofacial Surgery, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA aut Zhou Xiaofeng Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Room 530C, 60612, Chicago, IL, USA aut Human Genetics Springer-Verlag 129/2(2011-02-01), 189-197 0340-6717 129:2<189 2011 129 439 https://doi.org/10.1007/s00439-010-0915-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-010-0915-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Jiang Lu Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Room 530C, 60612, Chicago, IL, USA aut NATIONALLICENCE 700 1- Dai Yang Department of Bioengineering, College of Engineering, University of Illinois at Chicago, Chicago, IL, USA aut NATIONALLICENCE 700 1- Liu Xiqiang Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Room 530C, 60612, Chicago, IL, USA aut NATIONALLICENCE 700 1- Wang Cheng Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Room 530C, 60612, Chicago, IL, USA aut NATIONALLICENCE 700 1- Wang Anxun Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Room 530C, 60612, Chicago, IL, USA aut NATIONALLICENCE 700 1- Chen Zujian Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Room 530C, 60612, Chicago, IL, USA aut NATIONALLICENCE 700 1- Heidbreder Caroline Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Room 530C, 60612, Chicago, IL, USA aut NATIONALLICENCE 700 1- Kolokythas Antonia Department of Oral and Maxillofacial Surgery, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA aut NATIONALLICENCE 700 1- Zhou Xiaofeng Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, 801 S. Paulina Street, Room 530C, 60612, Chicago, IL, USA aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 129/2(2011-02-01), 189-197 0340-6717 129:2<189 2011 129 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer