ABSTRACT
The article titled "CircCPA4 Promotes the Malignant Phenotypes in Glioma via miR-760/MEF2D Axis", written by Yunjuan Zhang, Zengyan Cai, Jin Liang, Erqing Chai, Anqing Lu, Yinwu Shang was originally published electronically on the publisher's internet portal (currently SpringerLink) on 17 October 2020 with open access.
ABSTRACT
Circular RNA carboxypeptidase A4 (circCPA4) has been shown to involve in the tumorigenesis of glioma. However, the function and the molecular mechanism of circCPA4 in glioma remain inadequate. Levels of circCPA4 and microRNA (miR)-760 were detected by quantitative real-time polymerase chain reaction. Cell proliferation, apoptosis, migration, and invasion were analyzed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), colony formation, flow cytometry, and transwell assays, respectively. Western blot was used to detect the protein levels of matrix metallopeptidase 2 (MMP2), MMP9 and myocyte enhancer factor 2D (MEF2D). The interaction between miR-760 and circCPA4 or MEF2D was analyzed by the dual-luciferase reporter assay or RNA pull-down assay. In vivo experiments were conducted using murine xenograft models. We found circCPA4 was highly expressed in glioma, and circCPA4 knockdown suppressed tumor cell proliferative, migratory and invasive behaviors, but enhanced cell apoptosis and radiosensitivity in glioma. CircCPA4 directly bound to miR-760 to suppress its expression, and miR-760 inhibition reversed circCPA4 knockdown-mediated inhibition of cell malignant phenotypes in glioma. MEF2D was a target of miR-760, and miR-760 performed anti-tumor effects by targeting MEF2D in glioma cells. Meanwhile, we found circCPA4 could indirectly regulate MEF2D by sponging miR-760. Importantly, xenograft analysis suggested that circCPA4 knockdown impeded tumor growth in vivo via regulating miR-760 and MEF2D. In conclusion, circCPA4 knockdown suppressed cell malignant phenotypes in glioma via miR-760/MEF2D axis to impede the progression of glioma, suggesting potential therapeutic targets for glioma treatment.
Subject(s)
Glioma/metabolism , MicroRNAs/metabolism , RNA, Circular/metabolism , Animals , Apoptosis/physiology , Cell Line, Tumor , Cell Movement/physiology , Cell Proliferation/physiology , Disease Progression , Gene Expression Regulation, Neoplastic/physiology , Gene Knockdown Techniques , Glioma/genetics , Humans , MEF2 Transcription Factors/metabolism , Mice, Inbred BALB C , Mice, Nude , RNA, Circular/geneticsABSTRACT
Transcriptional factors (TFs) are key regulators in orchestrating gene transcription during cancer development. However, their roles in glioma remain elusive. Here, we analyzed the differential expression of TFs and identified ZNF436 is upregulated in glioblastoma and Lower Grade Glioma patients. High expression of ZNF436 is positively associated with poor overall survival and regulated by CREB1 in glioma cells. Knockdown of ZNF436 significantly abolished glioma cells proliferation in vitro. RNA sequencing revealed that ZNF436 regulates cell cycle and controlling BCL10 expression. Overexpression of BCL10 promoted glioma cells growth and rescued the malignant behavior in ZNF436-knockdown cells. High levels of BCL10 also result in a worse prognosis in glioma patients. Taken together, our findings identify the CREB1/ZNF436/BCL10 axis represents a novel, potential therapeutic target for glioma interventions.