Long non-coding RNA MALAT-1 is downregulated in preeclampsia and regulates proliferation, apoptosis, migration and invasion of JEG-3 trophoblast cells.

Abstract

Long non-coding RNA (lncRNA), as a newly identified subset of the transcriptome, has been implicated in a variety of physiological and pathological processes. Metastasis associated lung adenocarcinoma transcript-1 (MALAT-1), a lncRNA that was initially detected in the metastatic lung cancer, was reported to be overexpressed in placenta previa increta/percreta (I/P), which is caused by excessive trophoblast invasion. However, the role of MALAT-1 in the regulation of trophoblast behavior is not fully understood. In this study, we first examined the expression of MALAT-1 in the placentas from the patients with preeclampsia, the pathology of which is associated with inadequate trophoblast invasion, and found that the expression of MALAT-1 was downregulated in the preeclamptic placentas as compared to the normal placentas. We further investigated the function of MALAT-1 in JEG-3 trophoblast cell line using short interfering RNA (siRNA) against MALAT-1 transcripts. Silencing of MALAT-1 in JEG-3 cells suppressed proliferation and induced cell cycle arrest at G0/G1 phase. Reduced expression of MALAT-1 by RNA interference resulted in enhanced apoptosis in JEG-3 cells, accompanied with elevated levels of the pro-apoptotic proteins including cleaved caspase-3, cleaved caspase-9 and cleaved poly (ADP-ribose) polymerase-1 (PARP-1). Moreover, the migration rate and the invasiveness of JEG-3 cells were suppressed when MALAT-1 was downregulated. In summary, our results suggest that MALAT-1 may play an important role in the regulation of proliferation, cell cycle, apoptosis, migration and invasion of trophoblast cells, and under-expression of MALAT-1 during early placentation may be involved in the pathogenesis of preeclampsia.

• Authors: Haiying Chen, Tao Meng, Xuemin Liu, Manni Sun, Chunxiao Tong, Jing Liu, He Wang, Juan Du
• Journal: International journal of clinical and experimental pathology (Int J Clin Exp Pathol) Vol. 8 Issue 10 Pg. 12718-27 ( 2015) ISSN: 1936-2625 [Electronic] United States
• PMID: 26722461 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MALAT1 long non-coding RNA, human
• RNA, Long Noncoding
• RNA, Small Interfering

Topics

• Apoptosis (genetics)
• Cell Line
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Down-Regulation
• Female
• Humans
• Placenta (metabolism, pathology)
• Placentation (genetics)
• Pre-Eclampsia (genetics, metabolism, pathology)
• Pregnancy
• RNA, Long Noncoding (genetics, metabolism)
• RNA, Small Interfering
• Trophoblasts (metabolism, pathology)