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Molecular profiling of long non-coding RNAs in prostate cancer cell lines

Dissertation (MSc (Medical Oncology))--University of Pretoria, 2023.

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Other Authors: Marima, Rahaba
Format: Thesis
Language:English
Published: University of Pretoria 2023
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access_status_str Open Access
author2 Marima, Rahaba
author_browse Marima, Rahaba
author_facet Marima, Rahaba
collection Thesis
dc_rights_str_mv © 2023 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria.
description Dissertation (MSc (Medical Oncology))--University of Pretoria, 2023.
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institution University of Pretoria (South Africa)
language English
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license_str Other — see source repository
provenance_str_mv Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository
publishDate 2023
publishDateRange 2023
publishDateSort 2023
publisher University of Pretoria
publisherStr University of Pretoria
record_format dspace
source_str UPSpace — University of Pretoria Institutional Repository
spelling oai:repository.up.ac.za:2263/91257 Molecular profiling of long non-coding RNAs in prostate cancer cell lines Marima, Rahaba mandisambeje@gmail.com Dlamini, Zodwa Kgoebane-Maseko, Mmamoletla Mbeje, Mandisa Pearl UCTD Prostate cancer lncRNAs Biomarker Bioinformatics Health sciences theses SDG-03 SDG-03: Good health and well-being Dissertation (MSc (Medical Oncology))--University of Pretoria, 2023. Prostate cancer (PCa) incidence rates continue to rise with an estimation of 375 000 deaths and 1.4 million new cases in the year 2020. It has become the second most commonly occurring cancer and the fifth most frequent cause of cancer-related deaths in men. Prostate cancer is also the leading cancer to occur in men in the sub-Saharan region. In PCa, the aberrant expression of certain RNA molecules has been linked to PCa progression. Non-coding RNAs (ncRNAs) are RNA transcripts that are known for their involvement in numerous cellular processes. They are important in tumorigenesis and their presence may indicate cancer progression stages. Long non-coding ribonucleic acids (lncRNAs) are transcripts with 200 or more nucleotides. The focus on these lncRNAs can be attributed to their involvement in each of the cancer “hallmarks”. There have been multiple studies that have successfully identified lncRNAs in PCa. However, the landscape of the enriched molecular pathways targeted by these lncRNAs remains to be elucidated. Thus, this study aimed to profile aberrantly expressed lncRNAs and map the biological pathways associated with PCa progression. The differential expression patterns of 86 lncRNAs were compared between PC-3 and LNCaP PCa cell lines, which are highly metastatic and low metastatic (high grade and low grade), respectively. This was achieved by comparing the expression of lncRNAs between PC-3 and LNCaP cells using a 384-well plate of PCa lncRNA gene panel. LncRNA differential gene expression patterns were determined using the CFX Maestro software. The lncRNAs with a ±2 up or downregulation were considered to be differentially expressed. Annotation and enrichment analysis of lncRNA differential gene expression was performed using a human lncRNA sets database, LncSEA and DIANA-miRPath. Based on the PrimePCR array results and bioinformatics analysis, TERC lncRNA was selected for validation. The results of the array were validated with RT-qPCR using TERC primers. Thirty-six (36) of 86 lncRNAs were shown to be upregulated, while 12/86 of the lncRNA panel were downregulated. Bioinformatics analysis revealed that the upregulated lncRNAs are involved in various hallmarks of cancer. Interestingly, HOTAIR and TUG1 were demonstrated to be exosomal lncRNAs. In addition, the hypermethylation of HOTAIR and TERC was shown to sponge various miRNAs, promoting tumour progression. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and the Gene Ontology (GO) analysis revealed several cancer-related pathways, namely the signalling pathways regulating pluripotency of stem cells and the TGF-beta signalling pathway. Cytoscape ceRNA network analysis further illustrated the lncRNA/miRNA/mRNA axis in PCa progression. LncRNAs may be prognostic biomarkers as they have been reported to be stable in liquid and solid biopsies. UP Research Development Programme (RDP) grant National Research Foundation (NRF) of South Africa South African Medical Research Council (SAMRC) em2025 Medical Oncology MSc (Medical Oncology) Unrestricted SDG-03: Good health and well-being 2023-07-04T09:50:44Z 2023-07-04T09:50:44Z 2023-09 2023 Dissertation Mbeje, MP 2023, Molecular profiling of long non-coding RNAs in prostate cancer cell lines, MSc dissertation, University of Pretoria, Pretoria, viewed yyymmdd http://hdl.handle.net/2263/91257 S2023 http://hdl.handle.net/2263/91257 DOI: https://doi.org/10.25403/UPresearchdata.23361050.v1 10.25403/UPresearchdata.23361050 en © 2023 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria
spellingShingle UCTD
Prostate cancer
lncRNAs
Biomarker
Bioinformatics
Health sciences theses SDG-03
SDG-03: Good health and well-being
Molecular profiling of long non-coding RNAs in prostate cancer cell lines
title Molecular profiling of long non-coding RNAs in prostate cancer cell lines
title_full Molecular profiling of long non-coding RNAs in prostate cancer cell lines
title_fullStr Molecular profiling of long non-coding RNAs in prostate cancer cell lines
title_full_unstemmed Molecular profiling of long non-coding RNAs in prostate cancer cell lines
title_short Molecular profiling of long non-coding RNAs in prostate cancer cell lines
title_sort molecular profiling of long non coding rnas in prostate cancer cell lines
topic UCTD
Prostate cancer
lncRNAs
Biomarker
Bioinformatics
Health sciences theses SDG-03
SDG-03: Good health and well-being
url http://hdl.handle.net/2263/91257