title: MicroRNA-135b suppresses extravillous trophoblast-derived HTR-8/SVneo cell invasion by directly down regulating CXCL12 under low oxygen conditions.
abstract: The expression of numerous microRNAs (miRNAs) in the trophoblasts changes under low oxygen conditions. However, little is known regarding the regulation of the trophoblast invasion by miRNAs under low oxygen conditions. The aim of this study was to identify those miRNAs and their target genes associated with the trophoblast invasion under low oxygen conditions. Culturing the extravillous trophoblast (EVT) cell line, HTR-8/SVneo, at 2% oxygen as compared to 20% oxygen suppressed trophoblast invasion that correlated with increased expression of microRNA-135b (miR-135b) and decreased expression of the its predicted target gene CXCL12. Overexpression of miR-135b suppressed CXCL12 mRNA expression and invasion of HTR-8/SVneo cells. Adding a neutralizing antibody against CXCL12 to the culture medium suppressed HTR-8/SVneo cell invasion. Reporter assays showed that the 3'UTR sequence of CXCL12 was directly targeted by miR-135b. Our results suggest that miR-135b and CXCL12 play important roles in modulating the EVT invasion under low oxygen conditions.
authors.affiliation: Department of Obstetrics and Gynecology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan; Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka City, Saitama 350-1298, Japan. Electronic address: stamaru@saitama-med.ac.jp.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Tamaru
authors.affiliation: Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka City, Saitama 350-1298, Japan. Electronic address: mizuno@saitama-med.ac.jp.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Mizuno
authors.affiliation: Department of Obstetrics and Gynecology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan; Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka City, Saitama 350-1298, Japan. Electronic address: hideno@saitama-med.ac.jp.
authors.forename: Hideno
authors.initials: H
authors.lastname: Tochigi
authors.affiliation: Department of Obstetrics and Gynecology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan. Electronic address: kajihara@saitama-med.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kajihara
authors.affiliation: Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka City, Saitama 350-1298, Japan; Division of Translational Research, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka City, Saitama 350-1298, Japan. Electronic address: okazaki@saitama-med.ac.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okazaki
authors.affiliation: Department of Obstetrics and Gynecology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan. Electronic address: ryugoo@saitama-med.ac.jp.
authors.forename: Ryugo
authors.initials: R
authors.lastname: Okagaki
authors.affiliation: Department of Obstetrics and Gynecology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan. Electronic address: ykamei@saitama-med.ac.jp.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Kamei
authors.affiliation: Department of Obstetrics and Gynecology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan. Electronic address: osamishr@saitama-med.ac.jp.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishihara
authors.affiliation: Department of Obstetrics and Gynecology, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan; Department of Obstetrics and Gynecology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: a-itakur@juntendo.ac.jp.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Itakura
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D015687:Cell Hypoxia; D002460:Cell Line; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000235:genetics*; D015536:Down-Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D054377:Chemokine CXCL12; C544965:MIRN135 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D010100:Oxygen
keywords: CXCL12; Invasion; Oxygen; Trophoblast; miR-135b