title: miR-21 downregulates the tumor suppressor P12 CDK2AP1 and stimulates cell proliferation and invasion.
abstract: The present study was undertaken to investigate the regulation of P12(CDK2AP1) by miRNAs. A conserved target site for miR-21 within the CDK2AP1-3'-UTR at nt 349-370 was predicted by bioinformatics software and an inverse correlation of miR-21 and CDK2AP1 protein was observed. Highly specific amplification and quantification of miR-21 was achieved using real-time RT-PCR. Transfection of HaCaT cells with pre-miR-21 significantly suppressed a luciferase reporter including the CDK2AP1-3'-UTR, whereas transfection of Tca8113 with anti-miR-21 increased activity of this reporter. This was abolished when a construct mutated at the miR-21/nt 349-370 target site was used instead. Anti-miR-21-transfected Tca8113 cells showed an increase of CDK2AP1 protein and reduced proliferation and invasion. Resected primary tumors and tumor-free surgical margins of 18 patients with head and neck squamous cell carcinomas demonstrated an inverse correlation between miR-21 and P12(CDK2AP1). This study shows that P12(CDK2AP1) is downregulated by miR-21 and that miR-21 promotes proliferation and invasion in cultured cells.
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, 145 West Changle Road, Xi'an 710032, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zheng
authors.forename: Hui
authors.initials: H
authors.lastname: Xue
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Yuegui
authors.initials: Y
authors.lastname: Jiang
authors.forename: Bei
authors.initials: B
authors.lastname: Liu
authors.forename: Jianhu
authors.initials: J
authors.lastname: Li
authors.forename: Yanpu
authors.initials: Y
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Moyi
authors.initials: M
authors.lastname: Sun
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D034622:RNA Interference; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C096151:CDK2AP1 protein, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; D008156:Luciferases