Construction of ceRNA and m6A-related lncRNA networks associated with anti-inflammation of AdipoAI

Hongwen Yu; Hongle Wu; Qiuyan Xie; Zining Liu; Zehao Chen; Qisheng Tu; Jake Chen; Fuchun Fang; Wei Qiu

doi:10.3389/fimmu.2022.1051654

Construction of ceRNA and m6A-related lncRNA networks associated with anti-inflammation of AdipoAI

Front Immunol. 2023 Jan 10:13:1051654. doi: 10.3389/fimmu.2022.1051654. eCollection 2022.

Authors

Hongwen Yu¹, Hongle Wu², Qiuyan Xie¹, Zining Liu¹, Zehao Chen¹, Qisheng Tu³, Jake Chen³, Fuchun Fang¹, Wei Qiu¹

Affiliations

¹ Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
² Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou, China.
³ Division of Oral Biology, Tufts University School of Dental Medicine, Boston, MA, United States.

Abstract

Background: Adiponectin (APN) is an endogenous adipokine secreted from adipocytes that exerts anti-inflammatory properties. AdipoAI is an orally active adiponectin receptor agonist identified by our group that can emulate APN's anti-inflammatory properties through mechanisms that are not fully understood. LncRNAs, a type of noncoding RNA more than 200 bp in length, have been demonstrated to have abundant biological functions, including in anti-inflammatory responses.

Materials and result: In the current study, we performed a lncRNA microarray in LPS-induced Raw264.7 cells that were prestimulated with AdipoAI and screened 110 DElncRNAs and 190 DEmRNAs. Enrichment analyses were conducted on total mRNAs and DEmRNAs, including GSVA, ssGSEA, GO/KEGG, GSEA, and PPI analysis. Among all these processes, endocytosis was significantly enriched. A coexpression analysis was built based on DElncRNAs and DEmRNAs. Then, using TargetScan and miRwalk to predict related microRNAs of DElncRNAs and DEmRNAs, respectively, we established competing endogenous RNA (ceRNA) networks including 54 mRNAs from 8 GO items. Furthermore, 33 m6A methylation-related marker genes were obtained from a previous study and used for the construction of an m6A-related lncRNA network by coexpression analysis. We identified FTO as the hub gene of the network and 14 lncRNAs that interacted with it. The expression levels of 10 lncRNAs selected from ceRNA and FTO-related lncRNA networks were validated with qRT‒PCR. Finally, macrophage phenotype scores showed that AdipoAI could attenuate the M2b and M2c polarization of macrophages and correlate with the above lncRNAs.

Conclusion: Our work reveals that lncRNAs might be involved in the anti-inflammation process of AdipoAI in LPS-induced macrophages through the ceRNA network and the epigenetic regulation of m6A. Mechanistically, these lncRNAs associated with AdipoAI might be related to endocytosis and polarization in macrophages and provide new candidates for the anti-inflammatory application of APN and its receptor agonist.

Keywords: AdipoAI; adiponectin; anti-inflammation; ceRNA; lipopolysaccharide; m6A related-lncRNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Epigenesis, Genetic
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Lipopolysaccharides
Mice
RAW 264.7 Cells
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / metabolism
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptors, Adiponectin* / agonists

Substances

Lipopolysaccharides
RNA, Long Noncoding
RNA, Messenger
Receptors, Adiponectin

Grants and funding

This research was supported by grants from the National Natural Science Foundation of China [82101024 (WQ)] and the Natural Science Foundation of Guangdong Province [2020A1515110027 (WQ), 2021A1515010854 (FF)].