N6-methyladenosine modification of B7-H3 mRNA promotes the development and progression of colorectal cancer

Rui Chen; Fei Su; Tao Zhang; Dongjin Wu; Jingru Yang; Quanlin Guan; Chen Chai

doi:10.1016/j.isci.2024.108956

N6-methyladenosine modification of B7-H3 mRNA promotes the development and progression of colorectal cancer

iScience. 2024 Jan 18;27(2):108956. doi: 10.1016/j.isci.2024.108956. eCollection 2024 Feb 16.

Authors

Rui Chen^{1

2}, Fei Su^{1

2}, Tao Zhang², Dongjin Wu³, Jingru Yang^{1

2}, Quanlin Guan^{1

4}, Chen Chai³

Affiliations

¹ The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
² Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
³ People's Hospital of Suzhou New District, Suzhou, Jiangsu 215000, P.R. China.
⁴ Department of Oncology Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.

Abstract

B7-H3 is a common oncogene found in various cancer types. However, the molecular mechanisms underlying abnormal B7-H3 expression and colorectal cancer (CRC) progression need to be extensively explored. B7-H3 was upregulated in human CRC tissues and its abnormal expression was correlated with a poor prognosis in CRC patients. Notably, gain- and loss-of-function experiments revealed that B7-H3 knockdown substantially inhibited cell proliferation, migration, and invasion in vitro, whereas exogenous B7-H3 expression yielded contrasting results. In addition, silencing of B7-H3 inhibited tumor growth in a xenograft mouse model. Mechanistically, our study demonstrated that the N6-methyladenosine (m6A) binding protein YTHDF1 augmented B7-H3 expression in an m6A-dependent manner. Furthermore, rescue experiments demonstrated that reintroduction of B7-H3 considerably abolished the inhibitory effects on cell proliferation and invasion induced by silencing YTHDF1. Our results suggest that the YTHDF1-m6A-B7-H3 axis is crucial for CRC development and progression and may represent a potential therapeutic target for CRC treatment.

Keywords: Biochemistry; Cancer; Molecular biology; Omics.