Phosphatase of regenerating liver maintains cellular magnesium homeostasis

Phosphatase of regenerating liver (PRL) is highly expressed in malignant cancers and promotes cancer progression. Recent studies have suggested its functional relationship with Mg²⁺, but the importance and molecular details of this relationship remain unknown. Here, we report that PRL expression is regulated by Mg²⁺ and PRL protects cells from apoptosis under Mg²⁺-depleted conditions. When cultured cells were subjected to Mg²⁺ depletion, endogenous PRL protein levels increased significantly. siRNA-mediated knockdown of endogenous PRL did not significantly affect cell proliferation under normal culture conditions, but it increased cell death after Mg²⁺ depletion. Imaging analyses with a fluorescent probe for Mg²⁺ showed that PRL knockdown severely reduced intracellular Mg²⁺ levels, indicating a role for PRL in maintaining intracellular Mg²⁺ We also examined the mechanism of augmented expression of PRL proteins and found that PRL mRNA transcription was stimulated by Mg²⁺ depletion. A series of analyses revealed the activation and the crucial importance of signal transducer and activator of transcription 1 in this process. Collectively, these results implicate PRL in maintaining cellular Mg²⁺ homeostasis.