Yang Xiangchou, Ye Haihao, He Muqing, Zhou Xiaohai, Sun Ni, Guo Wenjian, Lin Xiaoji, Huang He, Lin Ying, Yao Rongxin, Wang Hong
Department of Hematology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Department of Cardiology, Wenzhou TCM Hospital, Wenzhou, 325000, China.
Biochem Biophys Res Commun. 2018 Mar 25;498(1):207-213. doi: 10.1016/j.bbrc.2018.02.211. Epub 2018 Mar 1.
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.
多发性骨髓瘤（MM）是第二常见的血液系统恶性肿瘤，是一种无法治愈的疾病，其特征是恶性浆细胞在骨髓中积聚。尽管在理解MM的发病机制方面取得了很大进展，但代谢可塑性和耐药性在很大程度上仍不清楚。在本研究中，我们发现长链非编码RNA蛋白二硫键异构酶家族A成员3假基因1（PDIA3P）在MM中高表达，且与MM患者的生存率相关。PDIA3P通过葡萄糖-6-磷酸脱氢酶（G6PD）和磷酸戊糖途径（PPP）调节MM的生长和耐药性。从机制上讲，我们发现PDIA3P与c-Myc相互作用以增强其反式激活活性并与G6PD启动子结合，刺激G6PD表达和PPP通量。我们的研究确定PDIA3P是一种新型的与c-Myc相互作用的长链非编码RNA，并阐明了PDIA3P在MM代谢调节中的关键作用，为MM患者提供了一个潜在的治疗靶点。
