LncRNA MIAT Promotes Spinal Cord Injury Recovery in Rats by Regulating RBFOX2-Mediated Alternative Splicing of MCL-1

Overview

Journal Mol Neurobiol

Specialties Molecular Biology
Neurology

Date 2022 May 31

PMID 35641779

Authors

Xin He

Jianan Zhang

Yunshan Guo

Xiaowei Yang

Yunfei Huang

Dingjun Hao

Affiliations

Soon will be listed here.

Abstract

LncRNA myocardial infarction-associated transcript (MIAT) alleviates acute spinal cord injury (ASCI)-induced neuronal cell apoptosis, but the specific mechanism of it involved in regulating SCI progression needs further exploration. Here, a SCI rat model was established, followed by administration with adenovirus-mediated MIAT overexpression vector (Ad-MIAT) alone or together with Ad-RBFOX2 (RNA binding fox-1 homolog 2). The data indicated that MIAT overexpression promoted motor function recovery, improved morphology of injured tissues, and restrained neuron loss and cell apoptosis in SCI rats. Then, PC-12 cells were treated with HO to induce cell injury. And highly expressed MIAT suppressed HO-caused decrease in cell viability and increase in cell apoptosis. MIAT stabilized RBFOX2 protein expression by binding to RBFOX2, thereby promoting RBFOX2-induced upregulation of anti-apoptotic MCL-1L (myeloid cell leukemia sequence 1) and reduction of pro-apoptotic MCL-1S. And silencing RBFOX2 in vitro blocked the inhibitory effect of MIAT on cell apoptosis. Moreover, MCL-1-specific steric-blocking oligonucleotides (SBOs) were used to transfer the MCL-1 pre-mRNA splicing pattern from MCL-1L to MCL-1S. SBOs reversed the protection effect of RBFOX2 overexpression on HO-induced cell injury. Furthermore, overexpression of MCL-1L instead of MCL-1S facilitated autophagy activation in HO-stimulated cells. Interestingly, co-overexpression of MIAT and RBFOX2 had a better promoting effect on SCI recovery. In conclusion, MIAT mitigated SCI by promoting RBFOX2-mediated alternative splicing of MCL-1. Our findings might provide a promising therapeutic target for SCI.

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