Cell Death Dis: miR-4476/APC/beta-catenin/c-Jun positive feedback ring promotes the development of glioma

Glioma is one of the most common primary tumors of the central nervous system (CNS), accounting for 81% of all malignant brain tumors, associated with higher morbidity and mortalityAccording to the 2016 World Health Organization (WHO) classification of CNS tumors, gliomas can be classified as limited gliomas (WHO Class I) and diffuse immersion gliomas (WHO II-IV) depending on how they grow and the mutation altogether of the IDH (Isocitric acid dehydrogenase) geneAmong them, glioblastoma (GBM, WHO IV) is the most malignant primary brain tumor, accounting for about 45% of all gliomasHowever, the specific molecular mechanism stoic mechanism stoicism to regulate the development of glioma has yet to be clarifiedIt is urgent to better understand the occurrence and development of glioma, identify new prognostic molecular markers, and formulate a new treatment strategy for gliomaAlthough previous studies have found that multiple miRNAs are involved in regulating the malignant state of glioma, there are no studies on miR-4476In the study, the researchers found that miR-4476 was expressed in gliomas, promoting the proliferation, migration and invasion of glioma cellsfurther institutional studies have found that the negative regulatory factor APC (adenoma polyps gene) in the Wnt/beta-catenin signal transduction pathway is a direct target of miR-4476, which can mediate the carcinogenic effects of miR-4476 on gliomaOverexpression miR-4476 can raise the expression level of Wnt/beta-catenin signal transduction pathway downstream effect factor C-Junthe opposite, c-Jun can adjust the expression of miR-4476 forward by combining its upstream transcription starting point (TSS)In addition, in clinical sample studies, it was found that the increase in expression of miR-4476 was an adverse prognosis, which was positively correlated with the expression level of c-Jun and negatively correlated with APCin summary, the study showed that miR-4476 can be used as an enhancer for tumors, stimulating their own expression by directly targeting APC and promoting malignant progression of gliomas