Journal article
The snoRNA target of t(4;14) in multiple myeloma regulates ribosome biogenesis
FASEB bioAdvances, Vol.1(7), pp.404-414
07/2019
DOI: 10.1096/fba.2018-00075
PMCID: PMC6996358
PMID: 32095781
Abstract
The orphan small nucleolar RNA (snoRNA) ACA11 is overexpressed as a result of the t(4;14) chromosomal translocation in multiple myeloma (MM), increases reactive oxygen species, and drives cell proliferation. Like other snoRNAs, ACA11 is predominantly localized to a sub‐nuclear organelle, the nucleolus. We hypothesized that increased ACA11 expression would increase ribosome biogenesis and protein synthesis. We found that ACA11 overexpression in MM cells increased nucleolar area and number as well as argyrophilic nuclear organizing regions (AgNORs). Supporting these data, samples from t(4;14)‐positive patients had higher AgNORs scores than t(4;14)‐negative samples. ACA11 also upregulated ribosome production, pre‐47S rRNA synthesis, and protein synthesis in a ROS‐dependent manner. Lastly, ACA11 overexpression enhanced the response to proteasome inhibitor in MM cells, while no effect was found in response to high doses of melphalan. Together, these data demonstrate that ACA11 stimulates ribosome biogenesis and influences responses to chemotherapy. ACA11 may be a useful target to individualize the treatment for t(4;14)‐positive myeloma patients.
Details
- Title: Subtitle
- The snoRNA target of t(4;14) in multiple myeloma regulates ribosome biogenesis
- Creators
- Vanessa Oliveira - University of IowaNitin Mahajan - Washington University in St. LouisMelissa L. Bates - University of IowaChakrapani Tripathi - University of IowaKyusik Q. Kim - Washington University in St. LouisHani S. Zaher - Washington University in St. LouisLeonard B Maggi Jr - Siteman Cancer Center, Washington University School of MedicineMichael H. Tomasson - University of Iowa
- Resource Type
- Journal article
- Publication Details
- FASEB bioAdvances, Vol.1(7), pp.404-414
- DOI
- 10.1096/fba.2018-00075
- PMID
- 32095781
- PMCID
- PMC6996358
- NLM abbreviation
- FASEB Bioadv
- ISSN
- 2573-9832
- eISSN
- 2573-9832
- Number of pages
- 11
- Grant note
- M.H.T. (U54CA199092) ACS‐IRG U.S. National Institutes of Health (R01-CA174743; R01-CA175349) National Cancer Institute
- Language
- English
- Date published
- 07/2019
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Stead Family Department of Pediatrics; Fraternal Order of Eagles Diabetes Research Center; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984259653902771
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