m6A modification-mediated BATF2 suppresses metastasis and angiogenesis of tongue squamous cell carcinoma through inhibiting VEGFA

Haojie Wen; Jinyong Tang; Yi Cui; Minhua Hou; Juan Zhou

doi:10.1080/15384101.2022.2109897

m6A modification-mediated BATF2 suppresses metastasis and angiogenesis of tongue squamous cell carcinoma through inhibiting VEGFA

Cell Cycle. 2023 Jan;22(1):100-116. doi: 10.1080/15384101.2022.2109897. Epub 2022 Aug 10.

Authors

Haojie Wen^{1

2}, Jinyong Tang^{1

2}, Yi Cui^{1

2}, Minhua Hou^{1

2}, Juan Zhou^{1

2}

Affiliations

¹ Department of Otorhinolaryngology Head and Neck Surgery, The First People's Hospital of Chenzhou (Affiliated Chenzhou Hospital, Southern Medical University), Chenzhou, Hunan, China.
² Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Xiangnan University, Chenzhou, Hunan, China.

Abstract

The aim is to explore the underlying mechanism of basic leucine zipper ATF-like transcription factor 2 (BATF2) in tongue squamous cell carcinoma (TSCC). The expression of BATF2 in TSCC tissues and corresponding adjacent normal TSCC tissues, human TSCC cell lines (SCC-15 and CAL-27) and human normal tongue epithelial cells NTEC was detected. Then, SCC-15 cells with stable BATF2 knockdown and CAL-27 cells with BATF2 overexpression were established to investigate the functional effect of BATF2 on TSCC. Thereafter, the effect of BATF2 on TSCC angiogenesis and BATF2 m6A methylation was also examined. BATF2 was significantly downregulated in TSCC tissues and cell lines, and BATF2 overexpression could suppress growth, metastasis and angiogenesis of TSCC. Mechanistically, vascular endothelial growth factor A (VEGFA) was identified as a downstream gene of BATF2, and it was confirmed that BATF2 suppressed growth, metastasis and angiogenesis of TSCC via inhibiting VEGFA. In addition, the N6-methyladenosine (m6A) modification of BATF2 mRNA mediated by METTL14 suppressed its expression in TSCC. METTL14/BATF2 axis could serve as a novel promising therapeutic candidate against angiogenesis for TSCC.

Keywords: BATF2; Tongue squamous cell carcinoma; VEGFA; angiogenesis; cell metastasis; m6A.

Publication types

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

MeSH terms

Carcinoma, Squamous Cell* / pathology
Cell Line, Tumor
Cell Proliferation / genetics
Gene Expression Regulation, Neoplastic
Humans
Tongue / metabolism
Tongue / pathology
Tongue Neoplasms* / pathology
Vascular Endothelial Growth Factor A / metabolism

Substances

Vascular Endothelial Growth Factor A
VEGFA protein, human

Grants and funding

This work was supported by the Research Program Project of Hunan Health Committee in 2019 [grant number C2019001] and Science and technology development plan project of Chenzhou Municipal science and Technology Bureau [grant number zdyf201936].