EZH2 Promotes Glioma Cell Proliferation, Invasion, and Migration via Mir-142-3p/KCNQ1OT1/HMGB3 Axis : Running Title: EZH2 Promotes Glioma cell Malignant Behaviors.

in Molecular neurobiology by Yiming Zhang, Yong Yu, Lei Yuan, Baozhong Zhang

TLDR

  • This study looked at how a protein called EZH2 helps glioma cells grow, move, and invade. The researchers found that EZH2 helps these cells by controlling the expression of other proteins and genes. They also found that EZH2 can be targeted with drugs to stop its activity, which could potentially slow down or stop the growth of gliomas. The study also looked at how EZH2 works with other proteins and genes to help glioma cells grow and move. Overall, this study provides important information about the role of EZH2 in gliomas and could lead to the development of new treatments for this deadly brain tumor.

Abstract

This study investigates the role and molecular mechanism of EZH2 in glioma cell proliferation, invasion, and migration. EZH2, miR-142-3p, lncRNA KCNQ1OT1, LIN28B, and HMGB3 expressions in glioma tissues and cells were determined using qRT-PCR or Western blot, followed by CCK-8 assay detection of cell viability, Transwell detection of invasion and migration, ChIP analysis of the enrichment of EZH2 and H3K27me3 on miR-142-3p promoter, dual-luciferase reporter assay and RIP validation of the binding of miR-142-3p-KCNQ1OT1 and KCNQ1OT1-LIN28B, and actinomycin D detection of KCNQ1OT1 and HMGB3 mRNA stability. A nude mouse xenograft model and a lung metastasis model were established. EZH2, KCNQ1OT1, LIN28B, and HMGB3 were highly expressed while miR-142-3p was poorly expressed in gliomas. EZH2 silencing restrained glioma cell proliferation, invasion, and migration. EZH2 repressed miR-142-3p expression by elevating the H3K27me3 level. miR-142-3p targeted KCNQ1OT1 expression, and KCNQ1OT1 bound to LIN28B to stabilize HMGB3 mRNA, thereby promoting its protein expression. EZH2 silencing depressed tumor growth and metastasis in nude mice via the miR-142-3p/KCNQ1OT1/HMGB3 axis. In conclusion, EZH2 curbed miR-142-3p expression, thereby relieving the inhibition of KCNQ1OT1 expression by miR-142-3p, enhancing the binding of KCNQ1OT1 to LIN28B, elevating HMGB3 expression, and ultimately accelerating glioma cell proliferation, invasion, and migration.

Overview

  • The study investigates the role and molecular mechanism of EZH2 in glioma cell proliferation, invasion, and migration. The hypothesis being tested is that EZH2 plays a critical role in these processes and that its expression is regulated by miR-142-3p, lncRNA KCNQ1OT1, LIN28B, and HMGB3. The methodology used for the experiment includes qRT-PCR or Western blot to determine the expression of EZH2, miR-142-3p, lncRNA KCNQ1OT1, LIN28B, and HMGB3 in glioma tissues and cells, followed by CCK-8 assay detection of cell viability, Transwell detection of invasion and migration, ChIP analysis of the enrichment of EZH2 and H3K27me3 on miR-142-3p promoter, dual-luciferase reporter assay and RIP validation of the binding of miR-142-3p-KCNQ1OT1 and KCNQ1OT1-LIN28B, and actinomycin D detection of KCNQ1OT1 and HMGB3 mRNA stability. A nude mouse xenograft model and a lung metastasis model were established to test the hypothesis in vivo. The primary objective of the study is to understand the molecular mechanism of EZH2 in glioma cell proliferation, invasion, and migration and to identify potential therapeutic targets for the treatment of gliomas.

Comparative Analysis & Findings

  • The study found that EZH2, KCNQ1OT1, LIN28B, and HMGB3 were highly expressed while miR-142-3p was poorly expressed in gliomas. EZH2 silencing restrained glioma cell proliferation, invasion, and migration. EZH2 repressed miR-142-3p expression by elevating the H3K27me3 level. miR-142-3p targeted KCNQ1OT1 expression, and KCNQ1OT1 bound to LIN28B to stabilize HMGB3 mRNA, thereby promoting its protein expression. EZH2 silencing depressed tumor growth and metastasis in nude mice via the miR-142-3p/KCNQ1OT1/HMGB3 axis. The key findings of the study support the hypothesis that EZH2 plays a critical role in glioma cell proliferation, invasion, and migration and that its expression is regulated by miR-142-3p, lncRNA KCNQ1OT1, LIN28B, and HMGB3.

Implications and Future Directions

  • The study's findings have significant implications for the field of research and clinical practice. The identification of potential therapeutic targets for the treatment of gliomas, such as EZH2, KCNQ1OT1, LIN28B, and HMGB3, could lead to the development of new therapies for this deadly brain tumor. The study also highlights the importance of understanding the molecular mechanism of EZH2 in glioma cell proliferation, invasion, and migration, which could lead to the development of more effective treatments for gliomas. Future research directions could include further investigation of the role of EZH2 in glioma development and progression, the development of targeted therapies for EZH2, and the exploration of other potential therapeutic targets for the treatment of gliomas.
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