Metastasis associated lung adenocarcinoma transcript 1 is up-regulated in placenta previa increta/percreta and strongly associated with trophoblast-like cell invasion in vitro

Abstract

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.

Inhibitory effect of alpha-momorcharin and its PEGylated conjugates on the migration and invasion of human choriocarcinoma JAR cells via reduced matrix metalloproteinase-2 (MMP-2) activity

“…Similarly, 1.5 mg/ml PEG-α-MMC reduced the MMP-2 activity by about 30% compared with the control (P < 0.01). MMP-9 activity was hardly detectable in the control and tested groups, which disagreed with previous reports that detected active MMP-9 in media samples derived from JAR cell culture wells (Staff et al, 2000;Tseng et al, 2009). The incubation period with serum-free conditioned medium was insufficiently long for the active form of the enzyme to be degraded, which may account for the different results.…”

MALAT-1: A long non-coding RNA and its important 3' end functional motif in colorectal cancer metastasis

“…On the basis of these observations, we speculate that these mutations occur in relatively conserved and species homologous fragments of MALAT-1; therefore, they possibly relate to CRC development and metastasis. MALAT-1 is up-regulated in placenta percreta and is strongly associated with trophoblast-like cell invasion in vitro (27). MALAT-1 can promote cell migration and invasion.…”

Comparison of the Gene Expression Profiles Between Smokers With and Without Lung Cancer Using RNA-Seq

“…Several of those differentially expressed genes have important functions with lung, such as HBB and HBA2 genes are involved in oxygen transport from the lung to the various peripheral tissues (Wajcman et al, 1992;Sanna et al, 1994); MALAT1 (metastasis associated lung adenocarcinoma transcript 1) is a large and infrequently spliced non-coding RNA, it is associated with metastasis and positively regulates cell motility while the transcriptional and/or post-transcriptional regulation of motility-related genes Tseng, 2009;Guo, 2010). Other differentially expressed genes are related with various functions, IL1B are involved in the inflammatory response, being identified as endogenous pyrogens; SPC25 Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity; SDC4 is cell surface proteoglycan that bears heparan sulfate; MUC2 coats the epithelia of the intestines, airways, and other mucus membrane-containing organs and so on.…”