Bioinformatics analysis integrating metabolomics of m6A RNA microarray in intervertebral disc degeneration

Xiaoshuai Wang; Ningning Chen; Zefeng Du; Zemin Ling; Penghui Zhang; Jiaming Yang; Mohammed Khaleel; Anthony N Khoury; Jianwen Li; Songbo Li; Haoyang Huang; Xinwei Zhou; Yueyin Han; Fuxin Wei

doi:10.2217/epi-2020-0101

Bioinformatics analysis integrating metabolomics of m⁶A RNA microarray in intervertebral disc degeneration

Epigenomics. 2020 Aug;12(16):1419-1441. doi: 10.2217/epi-2020-0101. Epub 2020 Jul 6.

Authors

Affiliations

¹ Department of Orthopedics, The Seventh Affiliated Hospital of Sun Yat-sen University, No. 628, Zhenyuan Rd, Shenzhen, 518107, China.
² Department of Clinical Medicine, Zhongshan Medical College of Sun Yat-sen University, No. 74, Zhongshan Er Rd, Guangzhou, 510030, China.
³ Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510030, China.
⁴ Department of Orthopaedic Surgery, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.
⁵ Hip Preservation Center, Baylor University Medical Center at Dallas, TX 75390, USA.
⁶ Affiliated Dongguan People's Hospital of Southern Medical University, Dongguan, 523000, China.

PMID: 32627576
DOI: 10.2217/epi-2020-0101

Abstract

Aim: To explore the potential functions and mechanism of N⁶.methyladenosine (m⁶A) abnormality of RNAs in nucleus pulposus from the intervertebral disc degeneration (IDD). Materials & methods: We performed rat model, m⁶A epitranscriptomic microarray, bioinformatics analysis and metabolomics. Results: In IDD, most of the differentially methylated RNAs showed a significant demethylation situation. The competing endogenous RNA network LOC102555094/miR-431/GSK-3β combining downstream Wnt pathway were identified in bioinformatics analysis. For metabolomics, activation of Wnt pathway led to reprogramming of glucose metabolism and enzyme activation of PKM2. Finally, quantitative real-time PCR and methylated RNA immunoprecipitation coupled with quantitative real-time PCR revealed the positive correlation between demethylation of LOC102555094 and expression of both FTO and ZFP217. Conclusion:LOC102555094 might be demethylated by ZFP217, activating FTO and LOC102555094/miR-431/GSK-3β/Wnt played a crucial role in IDD.

Keywords: N6.methyladenosine; bioinformatics analysis; competing endogenous RNA; intervertebral disc degeneration; long noncoding RNA; microRNA.

Publication types

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

MeSH terms

Adenosine / analogs & derivatives*
Animals
Intervertebral Disc Degeneration / genetics*
Male
Microarray Analysis
RNA, Long Noncoding*
RNA, Messenger*
Rats, Sprague-Dawley

Substances

RNA, Long Noncoding
RNA, Messenger
N-methyladenosine
Adenosine