title: Novel functions and targets of miR-944 in human cervical cancer cells.
abstract: Altered expression of specific microRNAs (miRNAs) has been observed in human cervical cancer. However, the biological functions of many of these miRNAs are yet to be discovered. We previously showed that miR-944 is significantly more abundant in cervical cancer tissues than their normal counterparts. In this study, we investigated the functions and targets of miR-944 in human cervical cancer cells. MiR-944 is located in the intron of the tumor protein p63 (TP63) gene, which is frequently overexpressed in cervical carcinomas. Using gain- and loss-of-function experiments in vitro, we demonstrate that miR-944 promotes cell proliferation, migration and invasion, but has no effect on apoptosis, in human cervical cancer cells. To identify the targets of miR-944, we performed photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation followed by deep sequencing. Among the candidate targets, we validated HECW2 (HECT domain ligase W2) and S100PBP (S100P binding protein) as direct targets of miR-944 using luciferase reporter assays and western blot analysis. Our findings reveal novel functions and targets of miR-944 in human cervical cancer cells, which may provide new insights of its role in cervical carcinogenesis.
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Cancer Center Karolinska, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Hong
authors.initials: H
authors.lastname: Xie
authors.forename: Linkiat
authors.initials: L
authors.lastname: Lee
authors.forename: Patrick
authors.initials: P
authors.lastname: Scicluna
authors.forename: Ersen
authors.initials: E
authors.lastname: Kavak
authors.forename: Catharina
authors.initials: C
authors.lastname: Larsson
authors.forename: Rickard
authors.initials: R
authors.lastname: Sandberg
authors.forename: Weng-Onn
authors.initials: WO
authors.lastname: Lui
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D002448:Cell Adhesion; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D003432:Cross-Linking Reagents / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047468:Immunoprecipitation; D008156:Luciferases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014945:Wound Healing
chemical_list: D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D035683:MicroRNAs; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C496889:S100PBP protein, human; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D008156:Luciferases; C574377:HECW2 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: PAR-CLIP; cervical cancer; invasion; miR-944; migration; proliferation