Oncogenic Orphan Nuclear Receptor NR4A3 Interacts and Cooperates with MYB in Acinic Cell Carcinoma
Abstract
:1. Introduction
2. Results
2.1. AcCC Tumors Harbor Recurrent Translocations Involving the NR4A3 and NR4A2 Genes
2.2. Confirmation of t(4;9) Translocations by Fluorescence In Situ Hybridization
2.3. Transcriptome Analysis Reveals Heterogeneity in Acinic Cell Carcinoma
2.4. Gene Expression Analysis Reveals a Poor Survival Subgroup of AcCC Tumors
2.5. AcCC Tumors with t(4;9) Overexpress NR4A3 Protein, which Interacts with Myb
2.6. Transcriptional Cooperativity between NR4A3 and Myb
2.7. Cooperative Gene Activation by NR4A3 and Myb
2.8. NR4A3 and Myb Cooperate in Colony Formation Assays
3. Discussion
4. Materials and Methods
4.1. Tissue Collection
4.2. RNA Isolation and Sequencing
4.3. Data Analysis
4.4. Fluorescence In Situ Hybridization (FISH)
4.5. Protein Analysis by Western Blot
4.6. Plasmids
4.7. Cell Culture and Transfections
4.8. Co-immunoprecipitation and GST-Pulldown Assays
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Parameter | Number (%) | Fusion | p-Value | |
---|---|---|---|---|
(+) | (−) | |||
Age | ||||
35< | 3 (14) | 2 | 1 | 0.39 |
35≥ | 18 (86) | 16 | 2 | |
Sex | ||||
Male | 4 (19) | 3 | 1 | 1.00 |
Female | 17 (81) | 15 | 2 | |
Tumor size | ||||
3 cm< | 12 (57) | 11 | 1 | |
3 cm≥ | 9 (43) | 7 | 2 | 0.55 |
Rec/met | ||||
yes | 5 (24) | 5 | 0 | 1.00 |
no | 16 (76) | 13 | 3 | |
3-year survival | ||||
alive | 17 (81) | 15 | 2 | 1.00 |
dead | 4 * (17) | 3 | 1 |
Translocation | Case Number (%) | Fusion Type | Number |
---|---|---|---|
t(4;9) | 12 (57) | HTN3-NR4A3 | 3 * |
STATH-NR4A3 | 6 | ||
CSN2-NR4A3 | 1 | ||
FDCSP-NR4A3 | 1 | ||
CSN1S1-NR4A3 HTN3-MSANTD3 | 1 2 ** | ||
t(9:12) | 4 (19) | PRH1-NR4A3 | 1 |
PRB3-NR4A3 | 2 * | ||
PRB1-STX17 | 1 | ||
t(8;9) | 1 (5) | OXR1-NR4A3 | 1 |
t(2;4) | 1 (5) | HTN3-NR4A2 | 1 |
None | 3 (14) |
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Lee, D.Y.; Brayer, K.J.; Mitani, Y.; Burns, E.A.; Rao, P.H.; Bell, D.; Williams, M.D.; Ferrarotto, R.; Pytynia, K.B.; El-Naggar, A.K.; et al. Oncogenic Orphan Nuclear Receptor NR4A3 Interacts and Cooperates with MYB in Acinic Cell Carcinoma. Cancers 2020, 12, 2433. https://doi.org/10.3390/cancers12092433
Lee DY, Brayer KJ, Mitani Y, Burns EA, Rao PH, Bell D, Williams MD, Ferrarotto R, Pytynia KB, El-Naggar AK, et al. Oncogenic Orphan Nuclear Receptor NR4A3 Interacts and Cooperates with MYB in Acinic Cell Carcinoma. Cancers. 2020; 12(9):2433. https://doi.org/10.3390/cancers12092433
Chicago/Turabian StyleLee, David Y., Kathryn J. Brayer, Yoshitsugu Mitani, Eric A. Burns, Pulivarthi H. Rao, Diana Bell, Michelle D. Williams, Renata Ferrarotto, Kristen B. Pytynia, Adel K. El-Naggar, and et al. 2020. "Oncogenic Orphan Nuclear Receptor NR4A3 Interacts and Cooperates with MYB in Acinic Cell Carcinoma" Cancers 12, no. 9: 2433. https://doi.org/10.3390/cancers12092433