Files and links (1)
Oh_Mihyun_20255.26 MB
PDF Embargoed Access, Embargo ends: 31 Aug 2027
Dissertation
Structural and functional dissection of the oncogenic lncRNA SChLAP1
Doctor of Philosophy (Ph.D.), Drexel University
Jul 2025
DOI:
https://doi.org/10.17918/00011130
Abstract
Long non-coding RNAs (lncRNAs) play key roles in a range of biological processes and disease progression, yet their mechanisms of action remain understudied. One such lncRNA, Second Chromosome Locus Associated with Prostate-1 (SChLAP1), is overexpressed in malignant prostate cancer and is associated with unfavorable patient outcomes, including metastasis and increased mortality. In this study, we demonstrated that SChLAP1 possesses distinct structural domains and conserved regions that contribute to its function. We determined the secondary structure of SChLAP1 using SHAPE-MaP and DMS-MaP chemical probing approaches. Our in vitro secondary structural model revealed that SChLAP1 consists of two distinct secondary structural modules located at its 5' and 3' ends, both featuring highly structured regions. In vivo probing identified structurally stable regions, potential protein-binding hotspots, and regions that may undergo structural rearrangements specific to cellular contexts. Overexpression of the modules led to a notable increase in cancer cell proliferation and invasion, proving their functional significance in the oncogenicity of SChLAP1. Additionally, using pulldown assays, we identified MYSM1 as a novel protein-binding partner of SChLAP1. RNA-seq analysis revealed key pathways associated with SChLAP1. Together, we identified independent structured modules of SChLAP1 that are functionally relevant, and our findings suggest that MYSM1, by binding directly to one such module, may regulate gene expression associated with metastatic cancer. Our insights into the structural and functional landscape of SChLAP1 lay the groundwork for exploring more detailed molecular mechanisms behind SChLAP1, ultimately supporting its potential as a therapeutic target.
Metrics
15 Record Views
Details
- Title
- Structural and functional dissection of the oncogenic lncRNA SChLAP1
- Creators
- Mihyun Oh
- Contributors
- Srinivas Somarowthu (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xiv, 153 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; College of Medicine; Drexel University
- Other Identifier
- 991022075628304721