The expression of the let-7 miRNAs and Lin28 signalling pathway in human term gestational tissues

Abstract

IntroductionLabour and delivery are processes associated with inflammation within intrauterine and cervical tissues. The mechanisms that induce labour-associated changes and, in particular, the role of microRNAs (miRNAs) remain to be elucidated. MiRNAs are small non-coding RNAs that repress gene expression via mRNA degradation and translational repression. Let-7 miRNAs are negatively regulated by RNA-binding protein, Lin28, and both function downstream of NF-κB signalling. In non-gestational tissues, let-7 and Lin28 reportedy function as negative and positive regulators of IL-6 expression. We hypothesised that labour-associated inflammation involves the downregulation of let-7 miRNAs and upregulation of Lin28 expression. AimTo determine the expression of Lin28 protein and let-7 miRNA in human gestational tissue obtained before and after labour. MethodGestational tissues were collected from women at term by Caesarean section with and without labour and following normal vaginal delivery (n = 6 per group). Protein and RNA was extracted and Lin28 and let-7 miRNA expression was measured by Western blotting and real-time PCR. ResultsThe data obtained established that let-7 miRNA and Lin28 display tissue-specific expression: Lin28 was strongly expressed in the placenta and choriodecidua, but not measurable in amnion; and let-7b and -7c expression were significantly lower in choriodecidua compare to placenta and amnion, whereas the amnion expressed less let-7d and -7f than other tissues. ConclusionWhile the expression of Lin28 protein and let-7 miRNA did not vary significantly with labour onset and delivery, changes in their bioactivity and impact on nuclear signalling pathways in human gestational tissues remain to be established.