Mol. Hum. Reprod. Advance Access originally published online on August 18, 2009
Molecular Human Reproduction 2009 15(11):725-731; doi:10.1093/molehr/gap071
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Metastasis associated lung adenocarcinoma transcript 1 is up-regulated in placenta previa increta/percreta and strongly associated with trophoblast-like cell invasion in vitro
1Department of Obstetrics and Gynecology, and Taichung Veterans General Hospital, 160, Section 3, Taichung-Kang Road, Taichung 40705, Taiwan 2Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan 3 China Medical University, Taichung, Taiwan 4 Chung-Shan Medical University, Taichung, Taiwan 5 Hung-Kuang University, Taichung, Taiwan 6 National Yang-Ming University, Taipei, Taiwan
7 Correspondence address. Tel: +886-4-23741258; Fax: +886-4-23503021; E-mail: t1018{at}vghtc.gov.tw
Placenta previa increta/percreta (I/P) is a severe form of invasive placentation associated with massive peripartum hemorrhage, which often requires Cesarean hysterectomy. The pathogenesis of invasive placentation is multidimensional, involving decidual deficiency, endomyometrial damage and excessively deep trophoblast invasion into the uterus. In this study, annealing control primer–polymerase chain reaction (ACP–PCR) was used to identify differentially expressed genes, which may impair placentation resulting in placenta previa I/P. Placental tissues from I/P and non-increta/percreta (non-I/P) sites were concomitantly collected from patients undergoing Cesarean hysterectomy. After ACP–PCR experiments (three patients), the differentially expressed bands, consistently showing up- or down-regulated trends between each of the I/P and non-I/P tissue pairs, were cloned and sequenced. Human non-protein coding metastasis associated lung adenocarcinoma transcript 1 (MALAT-1) gene was identified. Real-time quantitative PCR (10 patients) confirmed significant overexpression of MALAT-1 in I/P samples (P = 0.005). To investigate the role of MALAT-1 gene in the regulation of trophoblast cell invasion, targeting of MALAT-1 mRNA expression with short interfering RNA (siRNA) in trophoblast-like BeWo, JAR and JEG-3 choriocarcinoma cells was performed. The invasion ability of these cells was significantly suppressed after siRNA silencing (P < 0.001), and this was not correlated with abnormal MMP-2 and MMP-9 enzyme activities. Our results suggest that MALAT-1 expression in placenta previa I/P is increased and its down-regulation inhibits trophoblast-like cell invasion in vitro. MALAT-1 might be involved in regulating trophoblast invasion during the development of advanced invasive placentation.
Key words: MALAT-1/non-coding RNA/placenta previa increta/percreta/siRNA
J.J. Tseng and Y.T. Hsieh contributed equally to this study. Submitted on May 15, 2009; resubmitted on August 6, 2009; accepted on August 14, 2009.