WTAP contributes to the tumorigenesis of osteosarcoma via modulating ALB in an m6A-dependent manner

Qiyong Pan; Jigang Lou; Penghui Yan; Xiaobiao Kang; Pengfei Li; Zongqiang Huang

doi:10.1016/j.ygeno.2023.110566

WTAP contributes to the tumorigenesis of osteosarcoma via modulating ALB in an m6A-dependent manner

Genomics. 2023 Jan 20:110566. doi: 10.1016/j.ygeno.2023.110566. Online ahead of print.

Authors

Qiyong Pan¹, Jigang Lou¹, Penghui Yan¹, Xiaobiao Kang¹, Pengfei Li¹, Zongqiang Huang²

Affiliations

¹ Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
² Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address: dr_zongqianghuang@163.com.

PMID: 36690262
DOI: 10.1016/j.ygeno.2023.110566

Abstract

Purpose: Osteosarcoma (OS) is a prevalent bone malignancy mainly occurred in adolescents. WTAP/N6-methyladenosine (m6A) modification is confirmed to be involved in OS progression. This study is conducted to bring some novel insights to the action mechanism of WTAP/m6A under the hidden pathogenesis of OS.

Methods: qRT-PCR was executed to evaluate the expression levels of WTAP and ALB. ALB protein level in OS cells was measured by western blotting. The content of m6A in total RNA was assessed by m6A quantification assay. Me-RIP and dual luciferase reporter assays confirmed the target relationship of WTAP with ALB. With the use of the wound healing, CCK-8, and transwell invasion assays, the functional relationship between WTAP and ALB in OS cells was confirmed. The influences of WTAP on tumor growth in vivo were performed in the xenograft model of mouse.

Results: WTAP was increased but ALB was diminished in OS tissues and/or cell lines. WTAP modulated ALB expression in an m6A-dependent manner. Silencing of WTAP retarded the development of OS via inhibiting cell viability, migration, invasion, and tumor growth. Knockdown of ALB exerted the opposite effects on OS progression. Additionally, ALB deficiency partially eliminated the inhibiting effects of WTAP silencing on cellular processes in OS.

Conclusions: This is the first report to clarify the interaction of WTAP/m6A with ALB in OS progression. These experimental data to some extent broadened the horizons of WTAP/m6A in the development of OS.

Keywords: ALB; N6-methyladenosine; Osteosarcoma; WTAP.