Construction of ceRNA network mediated by circRNAs screening from microarray and identification of novel biomarkers for myasthenia gravis

Xiaotong Kong; Tao Wu; Hanlu Cai; Zhimin Chen; Yu Wang; Ping He; Peifang Liu; Lei Li; Shanshan Peng; Fanfan Xu; Jianjian Wang; Huixue Zhang; Lihua Wang

doi:10.1016/j.gene.2024.148463

Construction of ceRNA network mediated by circRNAs screening from microarray and identification of novel biomarkers for myasthenia gravis

Gene. 2024 Apr 15:918:148463. doi: 10.1016/j.gene.2024.148463. Online ahead of print.

Authors

Xiaotong Kong¹, Tao Wu², Hanlu Cai¹, Zhimin Chen³, Yu Wang¹, Ping He⁴, Peifang Liu¹, Lei Li¹, Shanshan Peng¹, Fanfan Xu¹, Jianjian Wang⁵, Huixue Zhang⁶, Lihua Wang⁷

Affiliations

¹ Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China.
² Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
³ Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China; Department of Neurology, The Second Hospital of Harbin, Harbin, Heilongjiang Province, China.
⁴ Department of Neurology, The First Hospital of Harbin, Harbin, Heilongjiang Province, China.
⁵ Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China. Electronic address: wangjian_427@163.com.
⁶ Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China. Electronic address: zhanghuixue2009@163.com.
⁷ Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, China. Electronic address: wanglh211@163.com.

PMID: 38631652
DOI: 10.1016/j.gene.2024.148463

Abstract

Background: Recent studies have revealed that circRNA can serve as ceRNA to participate in multiple autoimmune diseases. Our study aims to explore the key circRNA as ceRNA and biomarker for MG.

Methods: We used circRNA microarray to explore differentially expressed circRNAs (DECs) from MG and compare with control. Then, we predicted the target miRNA associated with DECs and screened miRNAs by the algorithm of random walk with restart (RWR). Next, we constructed the circRNA-miRNA-mRNA ceRNA regulated network (CMMC) to identify the hub objects. Following, we detected the expression of hub-circRNAs by RT-PCR. We verify has_circ_0004183 (circFRMD4) sponging miR-145-5p regulate cells proliferation using luciferase assay and CCK-8.

Results: We found that the expression level of circFRMD4 and has_circ_0035381 (circPIGB) were upregulated and has_circ_0089153(circ NUP214) had the lowest expression level in MG. Finally, we proved circFRMD4 sponging miR-145-5p regulate Jurkat cells proliferation. CircFRMD4 take part in the genesis and development of MG via circFRMD4/miR145-5p axis.

Conclusions: We found that circFRMD4, circPIGB and circNUP214 can be considered as valuable potential novel biomarkers for AchR + MG. CircFRMD4 participate in the development of AchR + MG via targeting binding with miR-145-5p.

Keywords: Biomarker; CircRNA; Myasthenia gravis; ceRNA.