MIR193BHG inhibits the proliferation, migration and invasion of trophoblasts by upregulating p53

Abstract

Aberrant expression of long non-coding RNAs (lncRNAs) serves a crucial role in the biological function of trophoblasts and contributes to preeclampsia (PE). lncRNA MIR193BHG expression is increased in PE placental tissues. In the present study, the effects of MIR193BHG on the function of trophoblasts were assessed to elucidate its underlying molecular mechanisms. The subcellular localization of MIR193BHG in HTR-8/SVneo human first-trimester extravillous trophoblast cells was determined using a fluorescent in situ hybridization assay and by conducting nucleocytoplasmic separation. The effect of MIR193BHG knockdown or overexpression on proliferation, migration, invasion and apoptosis was evaluated in vitro using Cell Counting Kit-8, wound healing, Transwell and flow cytometry assays. RNA-sequencing, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and protein-protein interaction network construction were subsequently performed to screen the downstream molecules regulated by MIR193BHG. Finally, rescue experiments were conducted to ascertain whether MIR193BHG influenced the biological function of trophoblasts via p53. MIR193BHG was predominantly localized in the nucleus of HTR-8/SVneo cells and overexpression of MIR193BHG significantly inhibited proliferation, migration and invasion, while increasing the rate of apoptosis of HTR-8/SVneo cells. Knockdown of MIR193BHG had the opposite effect. Furthermore, overexpression of MIR193BHG led to increases in both mRNA and protein levels of p53 compared with the control group, and knockdown of p53 rescued the effects induced by overexpression of MIR193BHG on cell proliferation, migration and invasion, while partially counteracting its effects on apoptosis of HTR-8/SVneo cells. In conclusion, the findings of the present study suggested that MIR193BHG served a critical role in progression of PE by regulating the expression of p53, and may be a novel therapeutic target for PE.

Keywords: MIR193BHG; long non-coding RNA; p53; preeclampsia; trophoblast.