MicroRNA-135b suppresses extravillous trophoblast-derived HTR-8/SVneo cell invasion by directly down regulating CXCL12 under low oxygen conditions

• Published in: Biochemical and biophysical research communications Vol. 461; no. 2; pp. 421 - 426
• Main Authors: Tamaru, Shunsuke, Mizuno, Yosuke, Tochigi, Hideno, Kajihara, Takeshi, Okazaki, Yasushi, Okagaki, Ryugo, Kamei, Yoshimasa, Ishihara, Osamu, Itakura, Atsuo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.05.2015
• Subjects: 3' Untranslated Regions; Base Sequence; Cell Hypoxia; Cell Line; Cell Movement; Chemokine CXCL12 - genetics; CXCL12; Down-Regulation; Humans; Invasion; MicroRNAs - genetics; MicroRNAs - metabolism; miR-135b; Oxygen; Oxygen - metabolism; RNA, Messenger - genetics; Trophoblast; Trophoblasts - cytology; Trophoblasts - metabolism; Up-Regulation; Oxygen; miR-135b; Trophoblast; CXCL12; Invasion
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2015.04.055

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. •miR-135b was up-regulated at 2% oxygen as compared to 20% oxygen in the HTR-8/SVneo cells.•CXCL12 was down-regulated at 2% oxygen as compared to 20% oxygen in the HTR-8/SVneo cells.•Overexpression of miR-135b suppressed the invasion of the HTR-8/SVneo cells by down regulating CXCL12.•CXCL12 is a novel direct target gene of miR-135b.