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Published on: June 9, 2017
RAD23A promotes multiple myeloma cell survival through DNA damage response, proteostasis and enhanced metabolic
Hongxiu Liu1, Yihua Wang2, Xunru Liu1
1The Second Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China; Hematology department, The second hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
RAD23A protein is upregulated in multiple myeloma (MM) and drives cancer cell growth. Inhibiting RAD23A suppresses MM progression and enhances drug sensitivity, suggesting it as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Multiple myeloma (MM) is an incurable plasma cell malignancy.
- The role of RAD23A, involved in DNA repair and the ubiquitin-proteasome system, in MM is undefined.
Purpose of the Study:
- To investigate RAD23A expression, prognostic significance, and functional role in multiple myeloma.
- To explore RAD23A as a potential therapeutic target for MM.
Main Methods:
- Analysis of RAD23A expression in MM cohorts.
- Bioinformatic prediction of RAD23A functions using RNA-seq data.
- Experimental validation in MM cell lines (H929, RPMI8226) including flow cytometry, metabolic assays (OCR, ECAR, glucose uptake), and RNA sequencing.
Main Results:
- RAD23A is upregulated in MM, correlating with disease burden and stage.
- High RAD23A expression is linked to increased metabolic activity and protein transport in MM cells.
- RAD23A knockdown inhibited MM cell growth, induced DNA damage and ER stress, caused G2/M arrest and apoptosis, and sensitized cells to bortezomib.
Conclusions:
- RAD23A is upregulated in multiple myeloma and promotes cancer progression.
- RAD23A knockdown impairs MM cell metabolism and enhances sensitivity to bortezomib.
- RAD23A represents a potential therapeutic target for multiple myeloma treatment.
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