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

Abstract

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.

Keywords

• Classification Description
• Epigenetics
• Cell biology
• Cancer