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Down-regulated Long Noncoding RNA HOXA11-AS affects trophoblast cell proliferation and migration by regulating RND3 and HOXA7 expression in preeclampsia

By Yetao Xu, Dan Wu, Jie Liu, Zhonghua Ma, Bingqing Hui, Jing Wang, Yanzi chen, Sailan Wang, Yifan Lian, Lizhou Sun

Posted 20 Mar 2018
bioRxiv DOI: 10.1101/285643

The long noncoding RNA HOXA11-AS reveals abnormal expression in numerous human diseases. However, its function and biological mechanisms remain unclear in Preeclampsia (PE). In this study, we report that HOXA11-AS was significantly downregulated in preeclampsic placental tissues and could contribute to the occurrence and development of Preeclampsia. Silencing of HOXA11-AS expression could significantly suppress trophoblast cell growth and migration, whereas HOXA11-AS overexpression facilitated cell growth in HTR-8/SVneo, JEG3 and JAR cell lines. RNA-seq analysis also indicated that HOXA11-AS silencing preferentially regulated numerous genes associated with cell proliferation and cell migration. Mechanistic analyses showed that HOXA11-AS could recruit Ezh2 and Lsd1 protein, and regulate RND3 mRNA expression in nucleus. In cytoplasm, HOXA11-AS modulate HOXA7 expression by sponged miR-15b-5p, thus affecting trophoblast cell proliferation. Together, these resulting data confirm that aberrant expression of HOXA11-AS is involved in the occurrence and development of Preeclampsia, and may act as a prospective diagnosis and therapeutic target in PE.

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