Study Of The Effects Of MIAT-miR181b-CELF1 Axis On The Progression Of Glioma

Glioma is the most common and aggressive malignant tumor of the central nervous system and has a high rate of recurrence and mortality.Although there have been advances in multimodal treatments such as surgery,radiotherapy and chemotherapy,overall survival of most patients with glioma remains dismal.Therefore,there is a strong need for a better understanding of the occurrence and evolution of glioma at the genetic and molecular levels for identifying new therapeutic strategies.Current research suggests that epithelial-mesenchymal transition may play an important role in the development of glioma.evidence over the past 5 years has shown that lncRNAs and miRNAs have a significant function in tissue homeostasis and biological processes,including cancer progression.Both of the molecules play a important role in tumor EMT.This thesis aims to clarify how LncRNA MIAT can influence the tumorigenesis and progression of tumors through the interaction with downstream target molecules.Our previous study showed that MIAT and CELF1 are highly expressed in gliomas,and their expression levels are up-regulated with the increase of malignant degree of glioma.In vitro experiments confirmed MIAT play important roles on proliferation,apoptosis,Invasion and migration of glioma cells.Tissue and cell level verification showed that the expression of the RNA binding protein CELF1 was highly correlated with the expression of MIAT and increased with the degree of malignant glioma.However,the regulation of MIAT in the development of glioma is still unknown.Therefore,this study used RNA sequencing analysis of clinical glioma samples to screen for LncRNA molecules that were abnormally expressed in glioma tissues.After predicting the possible target molecules by sequence,the upstream and downstream relationships were verified in vitro.And MIAT-miR181b-CELF1 play a role on glioma proliferation and EMT and other phenotypes.This study have found that MIAT is highly expressed in glioma patients,and the candidate target molecules including CELF1 and miR181b are predicted by sequence prediction of MIAT.Finally,the hypothesis:this regulatory pathway influence the tumorigenesis and progression of tumors verified in animal experiments and clinical samples experments.The expression of miR181b was down-regulated in glioma tissues and negatively correlated with MIAT expression.In vitro assays have shown that knockdown of MIAT can inhibit glioma proliferation and EMT phenotype,promote apoptosis,and knockdown of miR181b can reverse the effect of MIAT on glioma EMT phenotype and proliferation and apoptosis;Knockdown of CELF1 also complements the effect of MIAT on gliomas,so it can be inferred that both miR181b and CELF1 are target molecules for MIAT.In the glioma nude mouse model,knockdown of miR181b was shown to complement the effect of MIAT knockdown on glioma growth and EMT phenotype in vivo.Human glioma tissue samples also confirmed that MIAT and CELF1 were highly expressed in gliomas and miR181b was lowly expressed.In conclusion,it can be inferred that the MIAT-miR-181b-CELF1 axis plays an important role in the regulation of tumor growth,apoptosis,invasion and migration during the development of glioma,which may provide new ideas and therapeutic targets for the diagnosis,treatment and prognosis of glioma.