Regulation of trophoblast cell functions by intracellular signalling molecules and microRNAs
Trophoblast cells (TC) play a major role during pregnancy. Several growth factors influence trophoblast behavior, such as Epidermal Growth Factor (EGF). Although studies have showed the role of EGF and STAT5 in regulation of TC, interaction between both molecules has not yet been studied. STATs are also regulated by microRNAs (miRNAs). Evidence confirms that miRNAs are packed and released by TC in extracellular membrane vesicles (EMVs) which appear to mediate intercellular communication. Some miRNAs are expressed abundantly in placenta and their dysregulation may be involved in diseases as preeclampsia (PE). In this study we to analyze the axis STAT5/EGF in TC functions. Moreover, role of miR-134 and -141 in controlling proliferation and invasion was investigated. miR-141 expression was analyzed in EMVs and their effects on immune cells. The miR-141 levels was analyzed in normal and PE tissues. Primary TC and HTR8/SVneo expressed high STAT5 levels but it was lower in JAR cells. STAT5/EGF increased proliferation and viability in both cell lines. STAT5 knockdown decreased cell viability induced by EGF. STAT5 silencing induced a decreased HTR8/SVneo invasion and its effect could not be rescued by EGF. miR-134 inhibition suppressed invasion of TC whilst its overexpression decreased proliferation in HTR8/SVneo cells. miR-141 was up-regulated in PE tissues. miR-141 inhibition revealed reduced JEG3 viability and reduced invasion capability of both cell lines. After miR-141 overexpression, HTR8/SVneo cells secreted EMVs with increased miR-141 content. Incubation of EMVs with non-transfected HTR8/SVneo cells did not alter invasion, incubation with Jurkat cells reduced their proliferation. The axis EGF/STAT5 controls fundamental trophoblast functions for placentation and miR-141 regulates trophoblast invasion, such in turn may play an important role in intracellular communication using EMVs. In addition, it appears also elevated in PE patients and may have potential as biomarker.