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
Affiliations
Han Li
Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Gynecology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China
Liming Cai
International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, China
Qiuzhong Pan
Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
Xingyu Jiang
Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
Jingjing Zhao
Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
Tong Xiang
Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
Yan Tang
Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
Qijing Wang
Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
Jia He
Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
Desheng Weng
Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
Yanna Zhang
Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
Zhongqiu Liu
International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, China; Corresponding author
Jianchuan Xia
Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Corresponding author
Summary: 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.
