Alternative BNIP3 splicing in alveolar rhabdomyosarcomal cells

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dc.contributor.authorFernando, Amy
dc.contributor.examiningcommitteeWhyard, Steve (Biological Sciences)
dc.contributor.examiningcommitteeGhavami, Saeid (Human Anatomy and Cell Science)
dc.contributor.supervisorGordon, Joseph
dc.contributor.supervisorWilkins, Olivia
dc.date.accessioned2023-11-08T21:59:36Z
dc.date.available2023-11-08T21:59:36Z
dc.date.issued2023-04
dc.date.submitted2023-11-08T21:59:36Zen_US
dc.degree.disciplineBiological Sciencesen_US
dc.degree.levelBachelor of Science (B.Sc.)
dc.description.abstractSeveral cellular phenotypes drive tumorigenesis in alveolar rhabdomyosarcoma. These phenotypes may be attenuated via treatment with non-steroidal antiinflammatory drugs, like aspirin, tolfenamic acid, and indomethacin, which interfere with intracellular prostaglandin synthesis and induce cell death. Recent data suggest that this mechanism may be mediated by differential splicing of the cell death gene BNIP3, such that full-length BNIP3 could promote cell death, while short BNIP3 could inhibit it. Additional data indicate that oncogenic cytokines from the TGF-β family may also be involved in this mechanism. This honours thesis examines whether indomethacin alters cell death, BNIP3 splicing, and other alveolar rhabdomyosarcoma phenotypes. To assess this, RT-PCR and fluorescent imaging assays were performed on the RH30 cell line. Results of these experiments indicate that a 2.0 μM concentration of indomethacin alters the cell death phenotype. However, they also provide preliminary evidence that the expression levels of full-length and short BNIP3 are unchanged. Accordingly, drug treatments did not change calcium signalling pathways. Furthermore, this text examined the role of TGF-β cytokines in this molecular pathway. To help establish the role of TGF-β in alveolar rhabdomyosarcoma, a statistical analysis of a previously generated secretome dataset was performed. It determined that the three TGF-β isoforms are differentially secreted in alveolar and embryonal rhabdomyosarcoma. However, qRT-PCR results indicate that indomethacin exposure does not change TGF- β1 expression. Collectively, this thesis provides preliminary evidence that indomethacin exposure induces cell death in RH30s independently of alternative BNIP3 splicing.
dc.identifier.urihttp://hdl.handle.net/1993/37772
dc.language.isoeng
dc.rightsopen accessen_US
dc.subjectBNIP3 splicing
dc.subjectalveolar rhabdomyosarcoma
dc.subjectBNIP3
dc.titleAlternative BNIP3 splicing in alveolar rhabdomyosarcomal cells
dc.typebachelor thesisen_US
local.author.affiliationFaculty of Science::Department of Biological Sciences
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