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Investigating the mechanism of lncRNA SChLAP1 in prostate cancer
Thesis

Investigating the mechanism of lncRNA SChLAP1 in prostate cancer

Zoe Coutu
Master of Science (M.S.), Drexel University
Jun 2026
DOI:
https://doi.org/10.17918/00011527
pdf
Coutu_Zoe_20261.26 MB
PDF Embargoed Access, Embargo ends: 31 Aug 2028

Abstract

Cellular biology
Long non-coding RNAs (lncRNAs) have emerged as a class of molecules that play key roles in a number of biological processes and diseases, yet their mechanisms remain largely understudied. Second Chromosome Locus Associated with Prostate-1 (SChLAP1) is one such lncRNA that is overexpressed in prostate cancer (PCa) and is associated with worse patient outcomes. Previously published work in our lab defined the secondary structure of SChLAP1 and identified conserved functional regions including potential protein binding hotspots and locations that may undergo dynamic rearrangements in a cellular context. In PCa cell culture, overexpression of SChLAP1 has been shown to increase proliferation and invasion. In this study, we confirm the oncogenicity of SChLAP1 in the AR dependent LNCaP and 22Rv1 cell lines but demonstrate that the same effect is not seen in AR independent PC3 and Du145 cell lines. Similarly in the AR dependent cell lines, RNA-seq was used to identify differentially expressed genes associated with SChLAP1 overexpression, including upregulation of ribosomal biogenesis and protein synthesis pathways, and downregulation of olfactory transduction, interferon-gamma (IFN-[gamma]) response, and G-protein-coupled receptor (GPCR) signaling. RNA-seq in AR independent cell lines, however, did not have any differentially expressed genes upon SChLAP1 overexpression. Additionally, previous work in our lab [data not shown] identifies the histone H2A deubiquitinase and AR coregulator, MYSM1, as a novel protein binding partner of SChLAP1. Taken together, these results suggest a mechanism wherein SChLAP1 modulates AR signaling to promote PCa growth and progression. Our work on the structure and function of SChLAP1 lays out the groundwork for further investigation of its molecular mechanism and potential to be used as a therapeutic target or biomarker.

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