LncRNA MEG3 promotes the sensitivity of bortezomib by inhibiting autophagy in multiple myeloma. (December 2022)

• Record Type: Journal Article
• Authors: Zang, Xiaoyan; Wang, Jing; Xia, Yuan; Li, Jianyong; Chen, Lijuan; Gu, Yan; Shen, Xuxing
• Is Part Of: Leukemia research. Volume 123(2022)
• Publication Date: 2022-12
• Subjects: MEG3 -- ATG2B -- Autophagy -- Multiple myeloma; Leukemia -- Periodicals; Leukemia -- Periodicals; Leucémie -- Périodiques; Leukemia; Periodicals; Electronic journals; Electronic journals; 616.9941905
• DOI: 10.1016/j.leukres.2022.106967
• Languages: English
• ISSNs: 0145-2126

Abstract

Abstract: Background: Bortezomib resistance hampers the long-term survival of multiple myeloma (MM) patients. Our previous study has proved that downregulated lncRNA MEG3 is associated with the poor clinical outcome in MM. However, the effect of MEG3 on the sensitivity of bortezomib in MM and its possible molecular mechanism remains muddled. Methods: In this study, CCK8 and flow cytometry techniques were used to assess cell viability in MEG3 overexpressed MM cells after bortezomib treatment. The expression of autophagy-related protein LC3 and p62 were distinguished by Western blot, and the mCherry-GFP-LC3 puncta reflecting autophagy level was observed under fluorescence microscope. RNA immunoprecipitation (RIP) technology was used to detect the binding relationship of MEG3 and ATG2B to PTBP1. Results: Increased toxicity of bortezomib and diminished autophagy level were found in MEG3 overexpressed MM cells. Mechanistically, we discovered that RNA-binding protein PTBP1 could bind to MEG3 and ATG2B by RIP assay. Upregulation of MEG3 promoted PTBP1 expression and inhibited the expression level of ATG2B, suggesting that MEG3 recruited PTBP1 and then decayed ATG2B expression. Conclusion: In summary, our study illustrated that MEG3 increased bortezomib sensitivity by hindering autophagy through the PTBP1/ATG2B axis, providing a new therapeutic target for bortezomib-resistant MM patients. Highlights: LncRNA MEG3 promotes the sensitivity of bortezomib. MEG3 inhibits cell autophagy by disturbing ATG2B expression. MEG3 destabilizes ATG2B by recruiting RNA binding protein, PTBP1.