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Early-onset preeclampsia (PE) is a pregnancy complication that can lead to severe adverse maternal and fetal outcomes. However, the mechanisms underlying the development of early-onset PE are not fully understood. Ribosomal protein L39 (RPL39) is a member of the S39E family of ribosomal proteins that plays an important role in stem cell self-renewal, cancer metastasis, and chemoresistance. In this study, we aimed to explore the potential function of RPL39 in placental trophoblast cells. We analyzed the expression of RPL39 in early-onset PE and normal placental tissues using real-time PCR, western blot analysis, and immunohistochemistry. The results showed that RPL39 was markedly downregulated in early-onset PE placental tissues. RPL39 knockdown inhibited trophoblast cell proliferation, migration, and invasion, as well as placental explant outgrowth. Flow cytometry analysis suggested that knockdown of RPL39 resulted in cell cycle arrest at the G0/G1 phase, but had no significant effect on cell apoptosis. We also found that RPL39 knockdown could alter cell morphology. We then measured the expression of the epithelial cell marker E-cadherin following knockdown of RPL39 in Bewo and HTR8/SVneo cells. RPL39 knockdown increased the expression of E-cadherin. Furthermore, E-cadherin expression was upregulated in placental explant outgrowth tissues transfected with RPL39 small interfering RNA. In conclusion, RPL39 plays an essential role in proliferation, invasion, and migration of trophoblast cells by targeting E-cadherin. Our findings provide novel insight into the mechanisms underlying the occurrence of early-onset PE.

As shown in our previous study, cyclosporine A (CsA) promotes the proliferation, invasion and migration of villous trophoblasts, thus improving embryo implantation. In addition, the incidence of preeclampsia (PE) is decreased in patients with recurrent spontaneous abortion (RSA) and repeated implantation failure (RIF) treated with CsA during the first trimester. Abnormal function of extravillous trophoblasts (EVTs) in early pregnancy is recognized as the pathogenetic mechanism of PE. EVTs share homology and function with pre-villous trophoblasts and villous trophoblasts; thus, we hypothesized that CsA may have the same regulatory effect on EVTs. In this study, we investigated the effects of CsA on HTR-8/SVneo trophoblasts in the extravillous layer and explored the underlying mechanisms. QPCR and Western blot (WB) analyses were performed to detect expression alterations in relevant proliferation and invasion proteins in response to different concentrations of CsA. We used an Affymetrix IVT expression microarray to examine the target genes of CsA in preeclamptic placentas versus normal placentas. Our results showed that certain concentrations of CsA could promote the proliferation, invasion and migration of HTR8/SVneo cells. CsA was also found to promote the expression of titin, MMP9, EGFR, and PRR15. TRAIL may be a target gene for CsA-mediated regulation of EVTs. CONCLUSIONS: By promoting the expression of related proteins and regulating the functions of HTR8/SVneo cells, CsA can promote vascular recasting and placental function, which may affect the pathogenesis of PE.

Background Pre-eclampsia (PE) is a major cause of maternal and neonatal mortality and morbidity. Abnormal invasion of trophoblast cells is a major pathogenesis observed in PE. In the present study, we aimed to explore the association between forkhead box A1 (FOXA1) and early-onset pre-eclampsia (EOPE) and to determine the effects of FOXA1 on trophoblast cell apoptosis, migration and invasion. Methods Clinical data and placentas of patients with EOPE and normal pregnant women were collected in the First Affiliated Hospital of Hainan Medical College. The protein expression levels of FOXA1 in the clinical samples were evaluated by western blotting and immunohistochemistry. The effects of FOXA1 knockdown on HTR-8/SVneo cell apoptosis, migration and invasion were evaluated by flow cytometry, wound healing and transwell invasion assays, respectively. Results The western blot and immunohistochemical analysis showed that FOXA1 protein expression in placenta of EOPE group was significantly lower than that of normal group. The expression of FOXA1 in the placentas of EOPE and normal pregnant women was negatively correlated with systolic pressure and diastolic pressure. The expression of FOXA1 in EOPE and normal pregnant women was positively correlated with gestation weeks at delivery and neonatal birthweight. In vitro functional studies showed that silencing FOXA1 increased apoptosis, and inhibited the migration and invasion of HTR-8/SVneo cells. Conclusions Down-regulation of FOXA1 in the placentas may indicate poor prognosis of EOPE. Silencing of FOXA1 induced apoptosis in trophoblast cells, and impaired the migratory and invasive capacity of trophoblast cells. FOXA1 may represent a potential therapeutic target for EOPE.

Transient receptor potential vanilloid 6 (TRPV6) has been shown to promote caner proliferation in several solid tumors, leading to unfavorable clinical outcomes. Our study aimed to elucidate the clinical significance of TRPV6 in patients with early-stage cervical squamous cell carcinoma (CSCC). The mRNA expression of TRPV6 was measured in 12 paired early-stage CSCC specimens and six cervical carcinoma cell lines using quantitative real-time PCR (qRT-PCR). Western blotting and immunohistochemistry (IHC) were employed to examine the protein expression level of TRPV6 in four paired specimens, 175 paraffin-embedded early-stage CSCC specimens, and 50 normal cervical tissues (NCTs), respectively. Statistical analyses were performed to evaluate the clinical significance of TRPV6 expression. The expressions of TRPV6 mRNA and protein were both significantly downregulated in early-stage CSCC tissues and cervical cancer cell lines. IHC analyses revealed that TRPV6 was downregulated in 136 (77.7 %) of 175 early-stage CSCC specimens. Moreover, TRPV6 expression in early-stage CSCC was significantly correlated with the tumor stage (P

The expression of nearly all smooth muscle genes are controlled by serum response factor binding sites in their promoter regions. However, SRF alone is not sufficient for regulating smooth muscle cell development. It associates with other cardiovascular specific cofactors to regulate smooth muscle gene expression. Previously, we showed that the transcription co-factor CRP2 was a regulator of smooth muscle gene expression. Here, we report that CSRP2BP, a coactivator for CRP2, is a histone acetyltransferase and a driver of smooth muscle gene expression. CSRP2BP directly interacted with SRF, CRP2 and myocardin. CSRP2BP synergistically activated smooth muscle gene promoters in an SRF-dependent manner. A combination of SRF, GATA6 and CRP2 required CSRP2BP for robust smooth muscle gene promoter activity. Knock-down of Csrp2bp in smooth muscle cells resulted in reduced smooth muscle gene expression. We conclude that the CSRP2BP histone acetyltransferase is a coactivator for CRP2 that works synergistically with SRF and myocardin to regulate smooth muscle gene expression.