| Glioma has been seriously harmful to human health.The characters of malignant proliferation,immune escape,invasion and metastasis,chemotherapy resistance and self-renewal of glioma stem cells make glioma--especially glioblastoma – have poor prognosis and short survival time.How to find a rapid and effective therapeutic strategy focus on the characters of glioma is the key to the treatment.The present treatment strategies for gliomas display differences according to their different subtypes.Temozolomide has certain curative effect on glioma,however the higher expression and activity of MGMT in malignant glioblastoma leads to resistance.Therefore drug resistance of glioma is also an important barrier for its clinical treatment.MiRNAs,as the significant epigenetic regulatory factor,play multiple roles in a variety of cytological behaviors,such as cell proliferation,cell movement,directional development,and asymmetric development.More than 1000 miRNAs have been identified in mammals,most of which are highly conserved.Each kind of miRNAs has several to dozens of different downstream target genes,and the same gene is often regulated by different miRNAs.More than 1/3 of the transcripts in human cells are modified by miRNAs.A great deal of abnormal expression of miRNAs has been found in the course of the various tumors development.Multiple onco-miRs and antionco-miRs regulate tumor progression through different molecular pathways.As a kind of small molecules,miRNAs have many advantages,such as easy intervention,easy to convert into medicine,flexible administration,and multi targets.On the other hand,with the rapid development of nanotechnology,many nanomaterials can target tumor tissues with pH,chemokines,or specific molecular markers.The miRNAs,with light weight,can be easily carried by nanoparticles,permeate through the blood-brain barrier,invade into tumor tissue and play function.Therefore,miRNAs mediated glioma therapy is expected to be an effective method for future biological treatment and needs further research.In our previous study,the tissue samples collected from the Department of Neurosurgery of Xijing Hospital were detected by miRNA microarray.Some differentially expressed miRNAs in normal tissues and glioma tissues were obtained.Among these miRNAs,miR-144/miR-451 a is located at the same location in chromatin and is highly conserved and stably expressed in human and mouse.The cluster contains three mature miRNAs molecules,including miR-144-3p,miR-144-5p and miR-451 a.Many literatures reported that miR-144-3p and miR-451 a played suppressor roles in multi kinds of tumors.Moreover,miR-144-3p and miR-451 a belong to the same miRNAs cluster.Co-expression or co-inhibition of the miRNAs cluster has little interference on the physiological behaviors of normal cells.In this work,we focus on the relationship between miR-144/miR-451 a clusters expression and the glioma development;and the influence and mechanism of miR-144-3p inhibiting glioma cells proliferation invasion and medicine resistance through target genes.By cell biology and molecular biology experiments in vitro,we obtain the following conclusions:1,miR-144/miR-451 a cluster is highly conserved in mammals and transcribed at the same time;2,the expression of miR-144/miR-451 a cluster is lower in glioma tissues than normal tissues,and reduced gradually with the pathological grade increasing.The further research shows that the cluster level indicates the better prognosis;3,miR-144-3p can inhibit the proliferation,invasion and medicine resistance of glioma cells through target genes FOS and HGF.Overexpression of FOS or HGF can completely rescue and restore the role of miR-144-3p.In conclusion,our results reveal the correlation between the expression of miR-144-3p and miRNAs in the same cluster in different glioma tissues,as well as the relation to prognosis of glioma patients.We also confirm that miR-144-3p can inhibit the expression of target genes FOS and HGF,therefore regulate a variety of cellular behavior of glioma cells and suppress glioma development.It provides a theoretical basis and a new potential target for the molecular diagnosis and treatment for glioma,and has clinical value and significance. |
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