RNA-binding protein HuD is present in pancreatic β cells, where it controls insulin mRNA translation and insulin production. However, direct regulation of β-cell proliferation by HuD has not been studied. Here, I show that HuD negatively regulates β-cell proliferation by increasing p27 level. HuD silencing decreased p27 level, leading to increased β-cell proliferation. Conversely, HuD overexpression induced G1 arrest by enhancing p27 expression. HuD silencing also decreased p27 level, resulting in enhanced β-cell proliferation, in immortalized β cells lacking insulin receptor, suggesting that HuD regulates p27 level in insulin independent manner. Together with the discovery that intratumoral injection of HuD siRNA with the carriers promoted insulinoma growth by reducing p27 level, these results identify HuD as a pivotal regulator of pancreatic β-cell proliferation.
