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| Status |
Public on Jul 26, 2017 |
| Title |
The role of FAM46C in myeloma cells [array] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
FAM46C is one of the most recurrently mutated genes in multiple myeloma (MM), however its role in disease pathogenesis is not determined. Here we demonstrate that wild type (WT) FAM46C overexpression induces substantial cytotoxicity in MM cells. In contrast, FAM46C mutations found in MM patients abrogate this cytotoxicity indicating a MM survival advantage conferred by the FAM46C mutant phenotype. WT FAM46C overexpression downregulated IRF4, CEBPB, MYC and upregulated immunoglobulin (Ig) light chain and HSPA5/BIP. Furthermore, pathway analysis suggests that enforced FAM46C expression activates the unfolded protein response (UPR) pathway and induces mitochondrial dysfunction. In contrast, endogenous CRISPR FAM46C depletion enhanced MM cell growth and notably decreasing Ig light chain and BIP expression, activating of ERK and anti-apoptotic signaling and conferring relative resistance to dexamethasone and lenalidomide treatment. The genes altered in FAM46C depleted cells are enriched for signaling pathways regulating estrogen, glucocorticoid, B cell receptor signaling and ATM signaling. Together these results implicate FAM46C in myeloma cell growth and survival. FAM46C mutation contributes to myeloma pathogenesis and disease progression by perturbation in plasma cell differentiation and endoplasmic reticulum homeostasis.
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| Overall design |
To assess the gene expression changes induced by FAM46C depletion, three samples, including OCIMY5 cells harboring, respectively, control, FAM46C gRNA #1 and FAM46C #6 gRNA, were harvested and processed for gene expression analysis.
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| Contributor(s) |
Zhu YX, Shi CX, Wang X, Braggio E, Stewart AK |
| Citation(s) |
28619709 |
| Submission date |
May 26, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Xuewei Wang |
| Organization name |
Mayo Clinic
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| Street address |
200 1st street
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| City |
Rochester |
| ZIP/Postal code |
55902 |
| Country |
USA |
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| Platforms (1) |
| GPL17586 |
[HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [transcript (gene) version] |
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| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE99358 |
The role of FAM46C in myeloma cells |
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| Relations |
| BioProject |
PRJNA388198 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE99357_RAW.tar |
73.0 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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