LncRNA PDIA3P interacts with c-Myc to regulate cell proliferation via induction of pentose phosphate pathway in multiple myeloma

Multiple myeloma (MM), the second most common hematologic malignancy, is an incurable disease characterized by the accumulation of malignant plasma cells within the bone marrow. Though great progresses have been made in understanding the mechanisms of MM, metabolic plasticity and drug resistance remain largely unknown. In this study, we found lncRNA Protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P) is highly expressed in MM and is associated with the survival rate of MM patients. PDIA3P regulates MM growth and drug resistance through Glucose 6-phosphate dehydrogenase (G6PD) and the pentose phosphate pathway (PPP). Mechanistically, we revealed that PDIA3P interacts with c-Myc to enhance its transactivation activity and binding to G6PD promoter, stimulating G6PD expression and PPP flux. Our study identified PDIA3P as a novel c-Myc interacting lncRNA and elucidated crucial roles for PDIA3P in metabolic regulation of MM, providing a potential therapeutic target for MM patients. •LncRNA PDIA3P is highly expressed in MM and reduces the survival rate of MM patients.•PDIA3P regulates MM cell growth and is associated with drug resistance.•PDIA3P promotes cell proliferation and drug resistance through G6PD and the pentose phosphate pathway.•PDIA3P interacts with c-Myc to stimulate the expression of G6PD.