Lactoferrin suppresses the development of Type II diabetes-induced colon cancer via multi-dimensional regulation of NT5DC3
Although the relationship between type 2 diabetes (T2D) and the increased risk of colorectal carcinogenesis is widely defined in clinical studies, the therapeutics methods and molecular mechanism of T2D-induced colon cancer and how do hyperglycemia affect the progression is still unknown. Here, we identified a dietary compound lactoferrin as a key factor that alleviates T2D-induced colon cancer. Lactoferrin represses the colon cancer progression in vivo and in vitro. Mechanistically, lactoferrin-dependent cellular DNA methylation and RNA m6A profiling remodeling transcriptionally regulate NT5DC3 expression. WTAP plays a key role in regulating NT5DC3 m6A modification and subsequently controls NT5DC3 downstream target HKDC1 expression. Moreover, co-treatment lactoferrin and NT5DC3 antibody restrain the growth of tumors by altering the aberrant epigenetic markers. Strikingly, clinical blood samples analysis demonstrates NT5DC3 expression is required to direct the distinction of T2D or T2D-induced colon cancer with healthy humans. Together, our study reveals that lactoferrin act as a major factor to repress T2D-induced colon cancer thus, significantly expanding the landscape of natural dietary mediated tumor suppression.