circRUNX2.2, highly expressed in Marek's disease tumor tissues, functions in cis to regulate parental gene RUNX2 expression

Lulu Wang; Gang Zheng; Yiming Yuan; Ziyi Wang; Qinyuan Wang; Meng Sun; Junfeng Wu; Changjun Liu; Yongzhen Liu; Bo Zhang; Hao Zhang; Ning Yang; Ling Lian

Poultry Science (Oct 2024)

circRUNX2.2, highly expressed in Marek's disease tumor tissues, functions in cis to regulate parental gene RUNX2 expression

Lulu Wang,
Gang Zheng,
Yiming Yuan,
Ziyi Wang,
Qinyuan Wang,
Meng Sun,
Junfeng Wu,
Changjun Liu,
Yongzhen Liu,
Bo Zhang,
Hao Zhang,
Ning Yang,
Ling Lian

Affiliations

Lulu Wang: Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing 100084, China
Gang Zheng: Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
Yiming Yuan: Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
Ziyi Wang: Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
Qinyuan Wang: Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
Meng Sun: Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
Junfeng Wu: Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
Changjun Liu: Division of Avian Infectious Diseases, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China
Yongzhen Liu: Division of Avian Infectious Diseases, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China
Bo Zhang: Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
Hao Zhang: Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
Ning Yang: Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
Ling Lian: Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; Corresponding author:

Journal volume & issue: Vol. 103, no. 10
p. 104045

Abstract

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ABSTRACT: Marek's disease (MD), an immunosuppression disease induced by Marek's disease virus (MDV), is one of the significant diseases affecting the health and productive performance of poultry. The roles of circular RNAs (circRNAs) in MD development were poorly understood. In this study, we found a circRNA derived from exon 6 of RUNX family transcription factor 2 (RUNX2) gene, named circRUNX2.2, was highly expressed in chicken tumorous spleens (TS) induced by MDV. Through fluorescence in situ hybridization and nuclear-cytoplasmic separation assay, we determined circRUNX2.2 was mainly located in the nucleus. Knockout experiments confirmed that the flanking complementary sequences (RCMs) mediated its circularization. Gain of function assay and dual luciferase reporter gene assay revealed that circRUNX2.2 could promote the expression of RUNX2 via binding with its promoter region. RNA antisense purification assay and mass spectrometry assay showed circRUNX2.2 could recruit proteins such as CHD9 protein. Knocking down CHD9 expression decreased the expression of RUNX2 gene, which confirmed the positive regulation that circRUNX2.2 on RUNX2 expression was probably facilitated via recruiting CHD9 protein. Functional experiments showed that circRUNX2.2 promoted the proliferation of the MD lymphoma-derived chicken cell line, MDCC-MSB1, which confirmed the potential oncogenic role of circRNX2.2 in tumor development. In conclusion, we found that the RUNX2-derived circRUNX2.2 can positively regulate the transcription of the parental gene RUNX2 in a cis-acting manner. The high expression of circRUNX2.2 in MD tumor tissues indicated that it might mediate MD lymphoma progression.

Published in Poultry Science

ISSN: 0032-5791 (Print); 1525-3171 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Agriculture: Animal culture
Website: https://www.journals.elsevier.com/poultry-science

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