Tamaru Shunsuke, Mizuno Yosuke, Tochigi Hideno, Kajihara Takeshi, Okazaki Yasushi, Okagaki Ryugo, Kamei Yoshimasa, Ishihara Osamu, Itakura Atsuo
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.
Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka City, Saitama 350-1298, Japan.
Biochem Biophys Res Commun. 2015 May 29;461(2):421-6. doi: 10.1016/j.bbrc.2015.04.055. Epub 2015 Apr 17.
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.
在低氧条件下，滋养层细胞中多种微小RNA（miRNA）的表达会发生变化。然而，关于低氧条件下miRNA对滋养层细胞侵袭的调控作用，我们了解甚少。本研究的目的是鉴定与低氧条件下滋养层细胞侵袭相关的miRNA及其靶基因。与在20%氧气条件下培养相比，在2%氧气条件下培养绒毛外滋养层（EVT）细胞系HTR-8/SVneo会抑制滋养层细胞侵袭，这与微小RNA-135b（miR-135b）表达增加及其预测靶基因CXCL12表达降低相关。miR-135b的过表达抑制了CXCL12 mRNA表达以及HTR-8/SVneo细胞的侵袭。向培养基中添加抗CXCL12的中和抗体可抑制HTR-8/SVneo细胞的侵袭。报告基因检测表明，CXCL12的3'UTR序列直接被miR-135b靶向。我们的结果表明，miR-135b和CXCL12在低氧条件下调节EVT侵袭中发挥重要作用。
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