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Long non-coding RNA MALAT-1 is downregulated in preeclampsia and regulates proliferation, apoptosis, migration and invasion of JEG-3 trophoblast cells.
Int J Clin Exp Pathol 2015; 8(10):12718-27IJ

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+Show Affiliations

Department of Obstetrics, The First Affiliated Hospital of China Medical University Shenyang, People's Republic of China.Department of Obstetrics, The First Affiliated Hospital of China Medical University Shenyang, People's Republic of China.Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University Shenyang, People's Republic of China.Department of Obstetrics, The First Affiliated Hospital of China Medical University Shenyang, People's Republic of China.Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University Shenyang, People's Republic of China.Department of Obstetrics, The First Affiliated Hospital of China Medical University Shenyang, People's Republic of China.Department of Obstetrics, The First Affiliated Hospital of China Medical University Shenyang, People's Republic of China.Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University Shenyang, People's Republic of China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26722461

Citation

Chen, Haiying, et al. "Long Non-coding RNA MALAT-1 Is Downregulated in Preeclampsia and Regulates Proliferation, Apoptosis, Migration and Invasion of JEG-3 Trophoblast Cells." International Journal of Clinical and Experimental Pathology, vol. 8, no. 10, 2015, pp. 12718-27.
Chen H, Meng T, Liu X, et al. Long non-coding RNA MALAT-1 is downregulated in preeclampsia and regulates proliferation, apoptosis, migration and invasion of JEG-3 trophoblast cells. Int J Clin Exp Pathol. 2015;8(10):12718-27.
Chen, H., Meng, T., Liu, X., Sun, M., Tong, C., Liu, J., ... Du, J. (2015). Long non-coding RNA MALAT-1 is downregulated in preeclampsia and regulates proliferation, apoptosis, migration and invasion of JEG-3 trophoblast cells. International Journal of Clinical and Experimental Pathology, 8(10), pp. 12718-27.
Chen H, et al. Long Non-coding RNA MALAT-1 Is Downregulated in Preeclampsia and Regulates Proliferation, Apoptosis, Migration and Invasion of JEG-3 Trophoblast Cells. Int J Clin Exp Pathol. 2015;8(10):12718-27. PubMed PMID: 26722461.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long non-coding RNA MALAT-1 is downregulated in preeclampsia and regulates proliferation, apoptosis, migration and invasion of JEG-3 trophoblast cells. AU - Chen,Haiying, AU - Meng,Tao, AU - Liu,Xuemin, AU - Sun,Manni, AU - Tong,Chunxiao, AU - Liu,Jing, AU - Wang,He, AU - Du,Juan, Y1 - 2015/10/01/ PY - 2015/08/18/received PY - 2015/09/24/accepted PY - 2016/1/2/entrez PY - 2016/1/2/pubmed PY - 2016/10/14/medline KW - Long non-coding RNA KW - MALAT-1 KW - preeclampsia KW - trophoblast invasion KW - trophoblast proliferation SP - 12718 EP - 27 JF - International journal of clinical and experimental pathology JO - Int J Clin Exp Pathol VL - 8 IS - 10 N2 - 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. SN - 1936-2625 UR - https://www.unboundmedicine.com/medline/citation/26722461/Long_non_coding_RNA_MALAT_1_is_downregulated_in_preeclampsia_and_regulates_proliferation_apoptosis_migration_and_invasion_of_JEG_3_trophoblast_cells_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26722461/ DB - PRIME DP - Unbound Medicine ER -