Cellular responses to silencing of PDIA3 (protein disulphide-isomerase A3): Effects on proliferation, migration, and genes in control of active vitamin D.

The active form of vitamin D, 1,25-dihydroxyvitamin D 3 , is known to act via VDR (vitamin D receptor), affecting several physiological processes. In addition, PDIA3 (protein disulphide-isomerase A3) has been associated with some of the functions of 1,25-dihydroxyvitamin D 3. In the present study we used siRNA-mediated silencing of PDIA3 in osteosarcoma and prostate carcinoma cell lines to examine the role(s) of PDIA3 for 1,25-dihydroxyvitamin D 3 -dependent responses. PDIA3 silencing affected VDR target genes and significantly altered the 1,25-dihydroxyvitamin D 3 -dependent induction of CYP24A1, essential for elimination of excess 1,25-dihydroxyvitamin D 3. Also, PDIA3 silencing significantly altered migration and proliferation in prostate PC3 cells, independently of 1,25-dihydroxyvitamin D 3. 1,25-Dihydroxyvitamin D 3 increased thermostability of PDIA3 in cellular thermal shift assay, supporting functional interaction between PDIA3 and 1,25-dihydroxyvitamin D 3 -dependent pathways. In summary, our data link PDIA3 to 1,25-dihydroxyvitamin D 3 -mediated signalling, underline and extend its role in proliferation and reveal a novel function in maintenance of 1,25-dihydroxyvitamin D 3 levels. • We used gene silencing to study the roles of protein disulphide-isomerase A3 (PDIA3). • PDIA3 has been proposed to play a role in vitamin D-mediated signalling. • PDIA3 silencing affected growth in prostate cell lines independently of vitamin D. • PDIA3 silencing affected VDR target genes, including CYP24A1. • Thermostability of PDIA3 was increased by presence of active vitamin D. [ABSTRACT FROM AUTHOR]