miR-320a upregulation contributes to the development of preeclampsia by inhibiting the growth and invasion of trophoblast cells by targeting interleukin 4

Preeclampsia (PE) is a serious pregnancy-specific pathologic complication, and represents a primary cause of mother and fetus mortality. Abnormally expressed microRNAs (miRNAs) serve important regulatory roles in the development of PE. At present, the pathogenesis and molecular mechanism of PE remain unclear. The aim of the present study was to investigate the potential functions of miRNA (miR)-320a in the human extravillous trophoblast cell line HTR-8/SVneo and to identify the molecular mechanisms underlying miR-320a function. Reverse transcription-quantitative PCR was used in the present study to detect the levels of miR-320a in the placentas of 57 pregnant patients with PE and 57 healthy pregnant patients. The effects of miR-320a overexpression on the proliferation and invasion of HTR-8/SVneo cells were determined using MTT and Transwell invasion assays. Western blot analysis and dual luciferase reporter assay were used to identify the genes targeted by miR-320a. The present results suggested that miR-320a expression level was decreased in placentas of patients with PE and the expression level of miR-320a was found to be associated with the pathogenesis of PE (P<0.05). Overexpression of miR-320a using miR-320a mimics significantly inhibited cell proliferation and invasion in HTR-8/SVneo cells in vitro (P<0.05). Furthermore, interleukin (IL)-4 was identified to be a direct target gene of miR-320a. miR-320a could repress IL-4 expression by binding to its 3′ untranslated region (P<0.05). Mechanistic studies suggested that IL-4 was a functional target gene of miR-320a, and miR-320a upregulation inhibited the proliferation and invasion of HTR-8/SVneo cells by directly targeting IL-4 (P<0.05). Collectively, to the best of our knowledge, the present study is the first to suggest that miR-320a may be a downregulated miRNA during PE, and IL-4 may act as a functional target gene of miR-320a. The present study suggested that miR-320a upregulation was involved in the development of PE by inhibiting the proliferation and invasion of trophoblast cells by targeting IL-4, indicating that the miR-320a/IL-4 pathway may represent a novel therapeutic target for PE treatment.