title: Up-Regulation of miR-21 Is Associated with Cervicitis and Human Papillomavirus Infection in Cervical Tissues.
abstract: MicroRNA-21 (miR-21) is recognized as an oncomir and shows up-regulation in many types of human malignancy. The aim of this study was to investigate the association of miR-21 expression associated with HPV infection in normal and abnormal cervical tissues. Cervical tissue samples with different cytological or histopathological grades were investigated for HPV by PCR and for miR-21 and programmed cell death, protein 4 (PDCD4) expression using quantitative real-time PCR (qRT-PCR). Laser capture microdissection (LCM) of stromal and epithelial tissues and in situ hybridization (ISH) using locked nucleic acid (LNA) probes were performed on a subset of fixed specimens. Cell line experiments were conducted on fibroblasts stimulated in culture media from HeLa cells, which were then assessed for miR-21, PDCD4, IL-6 and α-SMA expression by qRT-PCR. Twenty normal cervical cell, 12 cervicitis, 14 cervical intraepithelial neoplastic I (CIN I), 22 CIN II-III and 43 cervical squamous cell carcinoma (SCC) specimens were investigated. miR-21 levels were significantly lower in normal than in abnormal tissues. The expression of miR-21 in HPV negative normal cytology was significantly lower than in HPV positive samples in abnormal tissue and SCC. The miR-21 expression was significantly higher in HPV negative cervicitis than HPV negative normal cells. LCM and ISH data showed that miR-21 is primarily expressed in the tumor-associated stromal cell microenvironment. Fibroblasts treated with HeLa cell culture media showed up-regulated expression of miR-21, which correlated with increased expression of α-SMA and IL-6 and with down-regulation of PDCD4. These results demonstrate that miR-21 is associated with HPV infection and involved in cervical lesions as well as cervicitis and its up-regulation in tumor-stroma might be involved in the inflammation process and cervical cancer progression.
authors.affiliation: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; HPV & EBV and carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Sureewan
authors.initials: S
authors.lastname: Bumrungthai
authors.affiliation: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; HPV & EBV and carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Tipaya
authors.initials: T
authors.lastname: Ekalaksananan
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont, United States of America.
authors.forename: Mark Francis
authors.initials: MF
authors.lastname: Evans
authors.affiliation: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; HPV & EBV and carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Peechanika
authors.initials: P
authors.lastname: Chopjitt
authors.affiliation: Department of Obstetrics and Gynecology, Khon Kaen Hospital, Khon Kaen, Thailand; HPV & EBV and carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Thumwadee
authors.initials: T
authors.lastname: Tangsiriwatthana
authors.affiliation: Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; HPV & EBV and carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Natcha
authors.initials: N
authors.lastname: Patarapadungkit
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; HPV & EBV and carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Pilaiwan
authors.initials: P
authors.lastname: Kleebkaow
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Sanguanchoke
authors.initials: S
authors.lastname: Luanratanakorn
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Bunkerd
authors.initials: B
authors.lastname: Kongyingyoes
authors.affiliation: Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Suchin
authors.initials: S
authors.lastname: Worawichawong
authors.affiliation: Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; HPV & EBV and carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Chamsai
authors.initials: C
authors.lastname: Pientong
mesh_terms: D000199:Actins / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000821:virology; D045744:Cell Line, Tumor; D002584:Cervix Uteri / Q000473:pathology / Q000821:virology*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000473:pathology / Q000821:virology; D006367:HeLa Cells; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D027383:Papillomaviridae / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D016601:RNA-Binding Proteins / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics*; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology; D002575:Uterine Cervicitis / Q000235:genetics* / Q000473:pathology / Q000821:virology*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D051017:Apoptosis Regulatory Proteins; D015850:Interleukin-6; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins