title: 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.affiliation: Department of Obstetrics, The First Affiliated Hospital of China Medical University Shenyang, People's Republic of China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Obstetrics, The First Affiliated Hospital of China Medical University Shenyang, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Meng
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University Shenyang, People's Republic of China.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Obstetrics, The First Affiliated Hospital of China Medical University Shenyang, People's Republic of China.
authors.forename: Manni
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University Shenyang, People's Republic of China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Tong
authors.affiliation: Department of Obstetrics, The First Affiliated Hospital of China Medical University Shenyang, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Obstetrics, The First Affiliated Hospital of China Medical University Shenyang, People's Republic of China.
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University Shenyang, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D010929:Placentation / Q000235:genetics; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology
chemical_list: C557041:MALAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering
keywords: Long non-coding RNA; MALAT-1; preeclampsia; trophoblast invasion; trophoblast proliferation