Human MiR-185 Reduces The Expression Of Var MRNA And Suppresses Plasmodium Falciparum-infected Erythrocytes Adherence By Targeting The Dbl

Malaria is a mosquito-borne infectious disease caused by parasitic protozoans of the Plasmodium type, and severely damages human health. Of the five Plasmodium that cause human malaria, Plasmodium falciparum is responsible for the vast majority of malaria deaths.Coevolution of the P. falciparum parasite and its human mature RBC host has given rise to a complex parasite-host interaction net work. miRNA is a small single stranded non-coding RNA molecule (-22nt) found in plants,animals and some viruses. In cytoplasm,mature miRNAs incorporate with a series of important proteins like Dicer、 Argonaute to form RNA-induced silencing complex (RISC) and play important roles in RNAi. Via base-pairing with complementary sequences mRNA molecules UTR or CDS lead to mRNA deadenylation、degradation and translational repression.Recently, study by LaMonte et al. has revealed that the host miR-451 and let-7i translocate into the parasite during the intraerythrocytic life cycle of P. falciparum. miR-451 integrated into P. falciparum PKA-R transcripts, led to reduced translation of the regulatory PKA subunit and contributed to malaria resistance. An gambiae aga-miR-305 regulates the anti-Plasmodium response and midgut microbiota, likely through post-transcriptional modification of immune effector genes. AAV8-Mediated in vivo Overexpression of miR-155 Enhances the Protective Capacity of Genetically Attenuated Malarial Parasites.The research achievement shows that host miRNA can regulate P. falciparum parasite gene and anti-malaria.A mass of human miR-185 was found in P. falciparum 3D7 in our laboratory pre-research. Human miR-185 directly targets var (pfl1955w)by binding to its dbl via targets prediction tool called TargetScanHuman. The research shows that microRNA-185 directly targets and rogen receptor and suppresses proliferation,invasion,migration and tumorigenicity of human prostate cancer cells. MicroRNA-185 suppresses tumor growth and progression by targeting the Sixl oncogene in human cancers. MicroRNA-185 Targets SOCS3 to Inhibit Beta-Cell Dysfunction in Diabetes. To explore the specific effect of human miR-185 target to var (pfl1955w) gene and the adhesion property of Plasmodium falciparum-infected erythrocytes. In vitro culture of P. falciparum parasites and 293T cells; construction of dual luciferase reporter plasmid and expression plasmid; Human miR-185 was transfected into human 293T cell with Lipofectamine 2000 and electrotransfered into P.falciparum 3D7 with Cytomix. Dual luciferase reporter assay validatie the var (pfl1955w) as human miR-185 target. Quantitative real-time PCR was used to check the mRNA expression level of var(pfl1955w). Cytoadherence assay to test adhesion property of P.falciparum-infected erythrocytes and endothelial cells. Results show that 50% transfection efficiency was determined using a FAM RNA oligonucleotide conjugated to Fluorescein and flow cytometry. Overexpression of human miR-185 decreased the luciferase activities which were expressed by plasmid containing dbl of var(pfl1955w) in 293T cell. The mRNA expression level of var(pfl1955w) was decreased in 293T cell and P.falciparum 3D7 by human miR-185 effect. Cytoadherence of P.falciparum-infected erythrocytes and endothelial cells was reduced. In conclusion, Human miR-185 reduces the mRNA expression level of var(pfl1955w) and suppresses P.falciparum-infected erythrocytes adhesion property by targeting the dbl.