MicroRNA 15a/16-1 As Post-transcriptional Regulators Of T Cell Activity And Proliferative Capacity
| dc.contributor.advisor | Hoffmann, Peter R. | |
| dc.contributor.author | Urena, Frank R. | |
| dc.contributor.department | Molecular Biosciences and Bioengineering | |
| dc.date.accessioned | 2022-07-05T19:58:46Z | |
| dc.date.available | 2022-07-05T19:58:46Z | |
| dc.date.issued | 2022 | |
| dc.description.abstract | Micro-RNA (miR) is a small RNA molecule whose origin comes from the genome. The miR serves as a post-transcriptional regulator of cellular processes. In this study, we investigated the miRs produced during T cell activation and the mRNAs they target. Following 18 hours of activation by T cell receptors, we measured 48 miRs decreased, and three miRs increased. The study focused on two of the decreased miRs (miR 15a/16-1) that play a role in B cell lymphomas, thus having the best potential to affect T cell proliferation and expansion. Using doxycycline-induced transgenes, we developed a mouse model to investigate the effects of exogenous miR 15a/16-1 on T cells using gain-of-function experiments. The model was also used to identify target mRNAs involved in the proliferation and expansion of T cells. We identified MEK1 as a significant miR-15a/16 target. As a result, MEK1 regulation by miR-15a/16-1, ERK1/2, and ELK1 protein phosphorylation levels were decreased 25 % and 50% respectively. In conclusion, these results suggest that T cell receptor (TCR) stimulation decreases miR-15a/16 levels early in T cell activation to facilitate increased MEK1, ERK1/2, and ELK1. This decrease in miR-15a/16-1 level promotes a robust proliferation capacity dependent on sustained activation of MEK1-ERK1/2-ELK1 signaling. | |
| dc.description.degree | Ph.D. | |
| dc.identifier.uri | https://hdl.handle.net/10125/102256 | |
| dc.language | eng | |
| dc.publisher | University of Hawaii at Manoa | |
| dc.subject | MicroRNA | |
| dc.subject | Mitogen-activated protein kinases | |
| dc.subject | Cell interaction | |
| dc.subject | T cells | |
| dc.title | MicroRNA 15a/16-1 As Post-transcriptional Regulators Of T Cell Activity And Proliferative Capacity | |
| dc.type | Thesis | |
| dc.type.dcmi | Text | |
| local.identifier.alturi | http://dissertations.umi.com/hawii:11285 |
Files
Original bundle
1 - 1 of 1
Loading...
- Name:
- Urena_hawii_0085A_11285.pdf
- Size:
- 3.72 MB
- Format:
- Adobe Portable Document Format