MiR 19a promotes proliferation and inhibits apoptosis of placental trophoblasts via PTEN pathway

Abstract

Purpose: To screen the micro-ribonucleic acids (miRNAs) in the pathological processes of preeclampsia (PE), and to assess their effects on the proliferation and apoptosis of HTR-8/SVneo cells.
 Methods: The miRNAs in PE patients and healthy puerperae were screened out using miRNA microarray assay, and verified through low-throughput quantitative reverse transcription- polymerase chain reaction (qRT-PCR). The effects of expression level of miR-19a on proliferation and cycle of HTR-8/SVneo cells were determined using cell counting kit (CCK)-8 assay and propidium iodide (PI) staining, respectively. The influence of the expression level of miR-19a on apoptosis of HTR-8/SVneo cells was evaluated using Annexin V-fluorescein isothiocyanate (FITC)/PI staining. Subsequently, luciferase reporter gene assay, CCK-8 assay and Annexin V-FITC/PI staining were conducted, respectively.
 Results: Serum miR-19a was significantly decreased in PE patients, and a high level of miR-19a led to increase in the proliferation of HTR-8/SVneo cells. Decreased level of miR-19a arrested HTR-8/SVneo cell cycle at G1 phase, while increase in the miR-19a level repressed the apoptosis of HTR-8/SVneo cells. The PTEN was a direct target of miR-19a, and overexpression of miR-19a promoted the activation of Akt signaling pathway, thereby significantly decreasing the expression levels of downstream phosphorylated p21/p21 (p-p21/p21), p-p27/p27 and p-glycogen synthase kinase-3 beta (GSK3β)/GSK3β. Compared with those in cells transfected with empty vectors, the pro-proliferative and anti-apoptotic effects of miR-19a weakened in HTR-8/SVneo cell lines with overexpressed PTEN.
 Conclusion: MiR-19a targets PTEN in order to activate Akt signaling pathway, thereby promoting proliferation, and inhibiting apoptosis of HTR-8/SVneo cells. This provides new drug targets that can be investigated for future treatment of PE.