# miR-101/METTL3 axis induces autophagy by interrupting FOXG1/EIF3J-AS1 binding in gliomas

## TL;DR

The study reveals how miR-101 and METTL3 regulate autophagy in gliomas through interactions with the lncRNA EIF3J-AS1 and transcription factor FOXG1.

## Contribution

Identifies a novel miR-101/METTL3 axis that modulates autophagy by disrupting EIF3J-AS1/FOXG1 binding in gliomas.

## Key findings

- EIF3J-AS1 is upregulated in glioblastoma and promotes tumor growth while inhibiting autophagy.
- METTL3 enhances EIF3J-AS1 m6A modification and its binding to FOXG1, suppressing autophagy via MIF downregulation.
- miR-101 suppresses METTL3, disrupting EIF3J-AS1-FOXG1 binding and restoring autophagy through MIF upregulation.

## Abstract

The role of autophagy in glioma remains controversial, with long non-coding RNAs (lncRNAs) playing a crucial role in its regulation. N6-methyladenosine (m6A) modification influences lncRNA expression and function. Specifically, lncRNA EIF3J-AS1 acts as an oncogene in glioma, yet the mechanisms driving its upregulation remain unclear. This study demonstrates that EIF3J-AS1 expression is significantly elevated in glioblastoma multiforme (GBM) compared to low-grade glioma (LGG) and normal brain tissue. RNA sequencing (RNA-seq) identified EIF3J-AS1 as a target of the tumor suppressor miR-101, with functional assays showing its role in promoting glioma cell proliferation, inhibiting autophagy, and enhancing tumorigenesis in vivo. Methylated RNA immunoprecipitation (MeRIP) and bioinformatics analyses confirmed m6A modification of EIF3J-AS1, which correlates positively with the m6A methyltransferase METTL3 in glioma tissues. Mechanistically, METTL3 promotes m6A-dependent binding of EIF3J-AS1 to the transcription factor FOXG1. RNA-seq screening further identified macrophage migration inhibitory factor (MIF), an autophagy-promoting gene, as a downstream target of both METTL3 and EIF3J-AS1. Functional validation revealed that the METTL3/EIF3J-AS1/FOXG1 axis suppresses autophagy via MIF downregulation. Conversely, miR-101-mediated suppression of METTL3 disrupts EIF3J-AS1-FOXG1 binding, restoring MIF expression and promoting autophagy. These findings highlight EIF3J-AS1 and METTL3 as potential therapeutic targets, with disruption of EIF3J-AS1-FOXG1 interactions representing a novel autophagy-modulating strategy for glioma treatment.