Long non-coding RNA RPAIN regulates the invasion and apoptosis of trophoblast cell lines via complement protein C1q

Abstract

Long non-coding RNAs (lncRNAs) are key regulatory molecules that are involved in a variety of biological processes and human diseases. Their impact on early onset preeclampsia remains unclear. In this study, we tested the expression of RPAIN (transcript variant 12 of RPA interacting protein, a non-coding RNA, NR_027683.1) in placenta tissues derived from 25 pregnant women with PE and 15 healthy pregnant women using quantitative real-time PCR. The effect of RPAIN on trophoblast proliferation, invasion, and apoptosis and the underlying mechanisms were examined in trophoblast cell lines (HTR-8/SVneo). The results showed that RPAIN expression levels were significantly increased in early onset preeclamptic placentas compared to normal controls. The proliferation and invasive abilities of the trophoblast cells were significantly inhibited, and the apoptosis abilities of the trophoblast cells were significantly promoted when RPAIN was overexpressed. In addition, the overexpression of RPAIN inhibited the expression of complement protein C1q. Furthermore, C1q overexpression rescued the decreased cell invasion and enhanced cell apoptosis in RPAIN-overexpressing trophoblast cells. Our results suggest that increased RPAIN levels may contribute to the development of preeclampsia through regulating trophoblast invasion and apoptosis via C1q. Therefore, we proposed RPAIN as a novel lncRNA molecule, which might contribute to the development of PE (preeclampsia) and might compose a potential diagnostic and therapeutic target for this disease.

Mechanistic Insight into Long Noncoding RNAs and the Placenta

“…A recent study has also shown that MEG3’s role in apoptosis and migration may be critical factor in regulating vascular smooth muscle cells during spiral artery remodelling [ 99 ]. Another lncRNA identified as altered in preeclampsia is RPAIN , which by qPCR was shown to be overexpressed in placentas from preeclamptic pregnancies when compared to uncomplicated controls [ 100 ]. Overexpression of RPAIN in HTR8/SVneo cells resulted in inhibition of proliferation and invasion.…”

“…Overexpression of RPAIN in HTR8/SVneo cells resulted in inhibition of proliferation and invasion. The authors went on to show that C1q, a protein that is important for trophoblast invasion and spiral artery remodelling, was also inhibited when RPAIN was overexpressed [ 100 ].…”

Down-regulated Long Noncoding RNAHOXA11-ASaffects trophoblast cell proliferation and migration by regulatingRND3andHOXA7expression in preeclampsia

“…Our previous study also demonstrated that lncRNA SPRY4-IT1 and MEG3 modulate trophoblast cell proliferation, apoptosis as well as tube formation, invasion and migration in this disorder [14,40,41]. Moreover, other lncRNAs, including ATB, Uc.187, RPAIN and so on, were reported to regulate trophoblast cell growth or/and invasion or/and apoptosis in PE [17,18,42]. Therefore, more and more potential PE-associated lncRNAs need to be identified, the functions of which require further exploration for their underlying biological mechanisms.…”

Long non‐coding RNA TUG1 regulates the migration and invasion of trophoblast‐like cells through sponging miR‐204‐5p

“…Recently, numerous lncRNAs such as RPAIN, MALAT‐1, SPRY4‐IT1, MEG3 and TUG1 have been reported to be abnormally expressed in placentas of PE patients; they may affect the proliferation and metastasis of trophoblast cells, thereby playing functional roles in the pathogenesis of PE. Nevertheless, the underlying mechanisms of these lncRNAs in PE are still largely unknown.…”