Alteration of long non-coding RNAs and mRNAs expression profiles by compound heterozygous ASXL3 mutations in the mouse brain

ABSTRACT

Compound mutations in the additional sex combs-like 3 (ASXL3) gene greatly impact the expression of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in mouse myocardial tissues. Little is known about ASXL3 mutation effects on lncRNAs and mRNAs expression in the cerebrum and cerebellum. This study aims to clarify this point using quantitative real-time polymerase chain reaction and Western blotting. Transcriptome analysis based on RNA-seq followed by bioinformatics analysis were used to compare lncRNA and mRNA expression profiles. Cell proliferation, cell cycle progression, and apoptosis were evaluated after silencing of ASXL3 expression using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4- sulfophenyl)-2 H-tetrazolium method and flow cytometry. Results showed that ASXL3 gene expression was decreased in the cerebrum and cerebellum of mice with ASXL3 P723R*P1817A mutations. We identified 319 lncRNAs and 252 mRNAs differentially expressed in the cerebrum of ASXL3 P723R*P1817A mutant mice. In the cerebellum of ASXL3 P723R*P1817A mutant mice, 5330 lncRNAs and 2204 mRNAs were differentially expressed. Differentially expressed lncRNAs and mRNAs were widely distributed across the mouse genome and were associated with various biological processes and pathways. ASXL3 silencing by siRNA transfection affected the proliferation, cell cycle progression, and apoptosis of neural cells. Therefore, the ASXL3 P723R*P1817A mutations greatly modify the lncRNA and mRNA expression profiles in the mouse cerebrum and cerebellum.

KEYWORDS:

• Long non-coding RNA profile
• messenger RNA profile
• additional sex combs-like 3
• cerebrum
• cerebellum

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics approval

All experimental procedures in this study were carried out following the guideline of the European Union Directive 2010/63/EU on the protection of animals used for scientific purposes and the NIH guidelines and were approved by the Animal Care and Use Committee of the Guangzhou Medical University.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Supplementary material

Supplemental data for this article can be accessed here

Highlights

1. The expression of lncRNAs and mRNAs is altered in ASXL3 mutant mouse cerebrum.

2. The expression of lncRNAs and mRNAs is also altered in ASXL3 mutant mouse cerebellum.

3. ASXL3 is involved in the proliferation, cell cycle, and apoptosis of neural cells

Additional information

Funding

This study was supported by the [National Natural Science Foundation of China] under Grant [numbers 81771594 and 81873836]; [Natural Science Foundation of Guangdong Province] under Grant [number 2019A1515012034]; the [Major Project of the Department of Science and Technology of Guangzhou] under Grant [number 201704020108].