N6-methyladenosine-modified VGLL1 promotes ovarian cancer metastasis through high-mobility group AT-hook 1/Wnt/β-catenin signaling

Han Li; Liming Cai; Qiuzhong Pan; Xingyu Jiang; Jingjing Zhao; Tong Xiang; Yan Tang; Qijing Wang; Jia He; Desheng Weng; Yanna Zhang; Zhongqiu Liu; Jianchuan Xia

doi:10.1016/j.isci.2024.109245

N⁶-methyladenosine-modified VGLL1 promotes ovarian cancer metastasis through high-mobility group AT-hook 1/Wnt/β-catenin signaling

iScience. 2024 Feb 16;27(3):109245. doi: 10.1016/j.isci.2024.109245. eCollection 2024 Mar 15.

Authors

Han Li^{1

2}, Liming Cai³, Qiuzhong Pan¹, Xingyu Jiang¹, Jingjing Zhao¹, Tong Xiang¹, Yan Tang¹, Qijing Wang¹, Jia He¹, Desheng Weng¹, Yanna Zhang¹, Zhongqiu Liu³, Jianchuan Xia¹

Affiliations

¹ Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
² Department of Gynecology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
³ International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, China.

Abstract

The main causes of death in patients with ovarian cancer (OC) are invasive lesions and the spread of metastasis. The present study aimed to explore the mechanisms that might promote OC metastasis. Here, we identified that VGLL1 expression was remarkably increased in metastatic OC samples. The role of VGLL1 in OC metastasis and tumor growth was examined by cell function assays and mouse models. Mechanistically level, METTL3-mediated N⁶-methyladenosine (m⁶A) modification contributed to VGLL1 upregulation in an IGF2BP2 recognition-dependent manner. Furthermore, VGLL1 directly interacts with TEAD4 and co-transcriptionally activates HMGA1. HMGA1 further activates Wnt/β-catenin signaling to enhance OC metastasis by promoting the epithelial-mesenchyme transition traits. Rescue assays indicated that the upregulation of HMGA1 was essential for VGLL1-induced metastasis. Collectively, these findings showed that the m⁶A-induced VGLL1/HMGA1/β-catenin axis might play a vital role in OC metastasis and tumor growth. VGLL1 might serve as a prognostic marker and therapeutic target against the metastasis of OC.

Keywords: Cancer; Cell biology; Classification Description; Epigenetics.