H19 Functions As A Competing Endogenous RNA To Regulate EMT By Sponging MiR-130a-3p In Glioma

Research background:Epithelial-mesenchymal transition(EMT),a biological process in which epithelial cells lose their cell polarity and cell-cell adhesion,and gain migratory and invasive properties to become mesenchymal cells.At present,EMT has also been shown to occur in a variety of epithelial tumor,such as breast cancer,colorectal cancer,ovarian cancer,prostate cancer and esophageal cancer etc.Gliomas occur in neuroectodermal tissue,is classified as neuroepithelial tumors,which is one of the most common malignant tumor in nervous system.Malignant glioma surrounded into the normal tissue in the early stage of tumor formation,which is the main reason for the malignant glioma progression and recurrence.Therefore,research focused on malignant glioma EMT play an important role in reverseing the malignant progression and reducing the recurrence.Long non coding RNA(IncRNA)is a class of non-protein coding transcripts with more than 200 base pairs in size。In recent years,many studies have found aberrant tlncRNA expression is closely related to the tumorigenesis and these IncRNA were involved in tumor growth,invasion and recurrence process.In this article,we showed H19 was significantly upregulated in maliganat glimoma cells and in the clinical maliganat glioma tissue samples compared to the low grade samples.Ectopic overexpression of H19 induced EMT program in LN229 glioma cells,however,knockdown H19 decreased EMT process in U87 and U251.In addition,knockdown H19 decreased the nude glima growth.Moreover,we found that H19 functions as a competing endogenous RNA to regulate EMT by sponging miR-130a-3p in glioma,which provide a theoretical basis for the molecular diagnosis and Precision Medicine of glioma in the future.Methods:1、The expression of H19 in the whole transcriptome sequencing data① The whole transcriptome sequencing data(CGGA、TCGA、REMBRADNT、GSE4290 and GSE16011)analysis:the expression of H19 in HGG and LGG.② qRT-PCR was used to measure the expreesion of H19 in 20 clinical glioma tissue samples.③ qRT-PCR was used to measure the expreesion of H19 in glioma cell lines2、Effect of H19 on invasion and migration ability and EMT processTo explore the effect overexpression H19 virus was transfected in LN229 and knockdown H19 virus was transfected in U87 and U251 on invasion and migration ability and EMT Markers3、H19 promotes the sternness of GSCs.To explore the effect overexpression H19 and knockdown H19 in glioma stem cells on the sternness of GSCs.4、orthotopic nude experiment in vivoTo explore the relationship between H19 and tumorigenesis and prognosis in vivo.5、H19 functions as a competing endogenous RNA to regulate EMT by sponging miR-130a-3p in glioma① The positive relationship between H19 and SOX4② miR-130a-3p targeted both H19 and SOX4③ H19 functions as a competing endogenous RNA to regulate EMT by sponging miR-130a-3pResults:H19 was highly upregulated in glioma tissues and glioma cell lines H19 induced EMT programH19 increased the ablitily of invasion and migration of glioma cell lines H19 promotes the sternness of GSCs.H19 could promote tumorigenesis in vivo.H19 functions as a competing endogenous RNA to regulate EMT by sponging miR-130a-3p in glioma.Conclusions:H19 is over-expressed in maligant glioma tissues and cells and it could predict the prognosis of patients with gliomas.H19/miR-130a-3p/SOX4 signaling pathway plays a important role in regulate EMT process in glioma.H19/miR-130a-3p/SOX4 signaling pathway confirm a new lncRNA-miRNA-mRNA RNA regulation mode existence,which provide a basis for glioma research in future.