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

Sun, L.; Xu, Y.; Wu, D.; Liu, J.; Ma, Z.; Hui, B.; Wang, J.; Chen, Y.; Wang, S.; Lian, Y.

doi:10.1101/285643

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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

Sun, L.·Xu, Y.·Wu, D.·Liu, J.·Ma, Z.·Hui, B.·Wang, J.·Chen, Y.·Wang, S.·Lian, Y.

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Abstract

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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Sun, L., Xu, Y., Wu, D., Liu, J., Ma, Z., Hui, B., Wang, J., Chen, Y., Wang, S., Lian, Y.. 2018-03-20. Down-regulated Long Noncoding RNA HOXA11-AS affects trophoblast cell proliferation and migration by regulating RND3 and HOXA7 expression in preeclampsia. https://doi.org/10.1101/285643

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