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
Affiliations
Rui Chen
The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu 730000, P.R. China; Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
Fei Su
The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu 730000, P.R. China; Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
Tao Zhang
Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
Dongjin Wu
People’s Hospital of Suzhou New District, Suzhou, Jiangsu 215000, P.R. China
Jingru Yang
The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu 730000, P.R. China; Department of Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
Quanlin Guan
The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu 730000, P.R. China; Department of Oncology Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China; Corresponding author
Chen Chai
People’s Hospital of Suzhou New District, Suzhou, Jiangsu 215000, P.R. China; Corresponding author
Summary: 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.
