METTL3 enhances cell adhesion through stabilizing integrin β1 mRNA via an m6A-HuR-dependent mechanism in prostatic carcinoma.
Ermao Li, Bo Wei, Xiaolan Wang, Ran Kang
Abstract
Bone metastasis is the major cause of morbidity and mortality in patients with prostate cancer (PCa). However, the underlying mechanism of bone-specific metastasis remain vague. Recently, with the deep research of N6-methyladenine (m6A) mRNA methylation, many studies directly focus on the role of m6A modification in human diseases, especially in cancers. Here we found that methyltransferase-like 3 (METTL3) expression is higher in PCa than in normal prostate tissues, especially in PCa with bone metastasis. High METTL3 expression was positively correlated with advanced progression and a poor prognosis of PCa. Functional assays demonstrated that METTL3 regulates the expression of Integrin β1 (ITGB1) through m6A-HuR-dependent mechanism, which affects the binding of ITGB1 to Collagen I and tumor cell motility, so as to promote the bone metastasis of PCa. The findings of this study reveal a novel mechanism of PCa osteotropism and suggest METTL3 as a therapeutic target for PCa bone metastasis.