MassIVE MSV000092169

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MYC as a Key Regulator of Protein Synthesis: Characterization of Downstream Targets in Multiple Myeloma

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Description

Multiple myeloma (MM) is a malignant plasma cell disorder and frequently characterized by the 16 dysregulation of the MYC oncogene, which is associated with poor prognosis and disease progression. While MYC's involvement in transcriptional regulation is well-established, the functional role of MYC target proteins and the impact on post-transcriptional processes in MM cells remain poorly understood. This study employed Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC) coupled with mass spectrometry analysis to investigate the effects of MYC depletion on the proteome of MM cells. The results revealed that MYC primarily regulates translational processes. Specifically, the three RNA-binding proteins (RBPs) 4EBP1, hnRNPC, and LARP1, were prominently down-regulated upon MYC depletion in MM cells. Notably, high expression levels of these proteins were correlated with poor survival and disease progression in MM patients. These findings highlight the critical role of MYC in the regulation of translation and identify 4EBP1, hnRNPC, and LARP1 as MYC target proteins. Targeting these proteins may offer new therapeutic strategies and prognostic markers for MM, potentially improving patient outcomes. This study provides valuable insights into the post-transcriptional regulatory mechanisms mediated by MYC and opens avenues for further research in understanding and treating this devastating disease. [doi:10.25345/C55717Z47] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Multiple Myeloma ; MYC target pathways ; RNA-binding proteins (RBPs) ; Cap-dependent translation

Contact

Principal Investigators:
(in alphabetical order) 		Frank Schnutgen, Department of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe-University Frankfurt, Germany
Submitting User: BHaeup

Publications

Seibert M, Koschade SE, Stolp V, Häupl B, Wempe F, Serve H, Kurrle N, Schnütgen F, von Metzler I.
The MYC-Regulated RNA-Binding Proteins hnRNPC and LARP1 Are Drivers of Multiple Myeloma Cell Growth and Disease Progression and Negatively Predict Patient Survival.
Cancers (Basel). Epub 2023 Nov 21.

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