SETDB1 induces lenalidomide resistance in multiple myeloma cells via epithelial‑mesenchymal transition and PI3K/AKT pathway activation

Xiao-li, Qian; Yang, Yang; Deng, Yingfen; Liu, Yali; Zhou, Yuwen; Fang, Han; Xu, Yilin; Yuan, Hongjian

doi:10.3892/etm.2023.11973

Cited by 5 publications

(1 citation statement)

References 58 publications

(62 reference statements)

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“…Additionally, many MTORC1 signaling genes directly targeted by ADA2B facilitate cancer growth and progression (Figure 3D) (He et al 2019b;Kiss et al 2020;Mo et al 2020;Zhao et al 2020;Shan et al 2022;Feng et al 2023). Known regulators of MM biology, such as EZH2, ITGB7, and SETDB1, were also among the ADA2B core targets (Neri et al 2011;Alzrigat et al 2018a;Qian et al 2023).…”

Section: Cell Cycle Related Genes Are Ada2b Core Targetsmentioning

confidence: 98%

The SAGA acetyltransferase module is required for the maintenance of MAF and MYC oncogenic gene expression programs in multiple myeloma

Chen,

Bhaskara,

et al. 2024

Preprint

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Despite recent advances in therapeutic treatments, multiple myeloma (MM) remains an incurable malignancy. Epigenetic factors contribute to the initiation, progression, relapse, and clonal heterogeneity in MM, but our knowledge on epigenetic mechanisms underlying MM development is far from complete. The SAGA complex serves as a coactivator in transcription and catalyzes acetylation and deubiquitylation. Analyses of datasets in the Cancer Dependency Map Project revealed many SAGA components are selective dependencies in MM. To define SAGA-specific functions, we focused on ADA2B, the only subunit in the lysine acetyltransferase (KAT) module that specifically functions in SAGA. Integration of RNA-seq, ATAC-seq, and CUT&RUN results identified pathways directly regulated by ADA2B include MTORC1 signaling, MYC, E2F, and MM-specific MAF oncogenic programs. We discovered that ADA2B is recruited to MAF and MYC gene targets, and that MAF shares a majority of its targets with MYC in MM cells. Furthermore, we found the SANT domain of ADA2B is required for interaction with both GCN5 and PCAF acetyltransferases, incorporation into SAGA, and ADA2B protein stability. Our findings uncover previously unknown SAGA KAT module-dependent mechanisms controlling MM cell growth, revealing a vulnerability that might be exploited for future development of MM therapy.

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