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An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
LncRNA PDIA3P interacts with c-Myc to regulate cell proliferation via induction of pentose phosphate pathway in
Xiangchou Yang1, Haihao Ye2, Muqing He1
1Department of Hematology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Abstract:
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.
Insights
This study identifies a novel long non-coding RNA, PDIA3P, highly expressed in multiple myeloma (MM). PDIA3P promotes MM growth and drug resistance by regulating Glucose 6-phosphate dehydrogenase (G6PD) via interaction with c-Myc.
Area of Science:
- Hematologic Malignancies
- Cancer Metabolism
- Molecular Biology
Background:
- Multiple myeloma (MM) is an incurable hematologic malignancy with poorly understood metabolic plasticity and drug resistance mechanisms.
- Understanding these mechanisms is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To investigate the role of long non-coding RNA Protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P) in MM.
- To elucidate the molecular mechanisms by which PDIA3P influences MM progression and drug resistance.
Main Methods:
- Quantitative real-time PCR to assess PDIA3P expression in MM.
- Analysis of the association between PDIA3P expression and patient survival.
- Investigating the interaction between PDIA3P, c-Myc, and Glucose 6-phosphate dehydrogenase (G6PD).
- Assessing the impact of PDIA3P on the pentose phosphate pathway (PPP) flux.
Main Results:
- PDIA3P is highly expressed in MM and correlates with patient survival.
- PDIA3P promotes MM growth and enhances drug resistance.
- PDIA3P interacts with c-Myc to upregulate G6PD expression and increase PPP flux.
- PDIA3P acts as a novel c-Myc interacting lncRNA.
Conclusions:
- PDIA3P plays a critical role in the metabolic regulation of MM.
- PDIA3P represents a potential therapeutic target for MM treatment.
- Targeting PDIA3P may overcome drug resistance in multiple myeloma.
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