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Probing the effects of Retinoblastoma Binding Protein 6 (RBBP6) knockdown on the sensitivity of cisplatin in cervical cancer cells
Dissertation (MSc (Genetics))--University of Pretoria, 2022.
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| Format: | Thesis |
| Language: | English |
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University of Pretoria
2022
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| _version_ | 1867613473429520384 |
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| access_status_str | Open Access |
| author2 | Moela, Pontsho |
| author_browse | Moela, Pontsho |
| author_facet | Moela, Pontsho |
| collection | Thesis |
| dc_rights_str_mv | © 2022 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 (Genetics))--University of Pretoria, 2022. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/86000 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:36:42.450Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2022 |
| publishDateRange | 2022 |
| publishDateSort | 2022 |
| 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:2263/86000 Probing the effects of Retinoblastoma Binding Protein 6 (RBBP6) knockdown on the sensitivity of cisplatin in cervical cancer cells Moela, Pontsho u16025483@tuks.co.za Ambele, Melvin Mehta, Harshini RBBP6 p53 Bcl-2 Cisplatin Cervical Cancer UCTD Dissertation (MSc (Genetics))--University of Pretoria, 2022. RBBP6 is considered a potential cancer biomarker due to its association with cell proliferation and overexpression at cervical cancer sites where there is marked apoptosis and elevated p53. More information is emerging regarding the role of RBBP6 in cancer treatment, specifically its potential to sensitize cancer cells to radiation and certain chemotherapeutic agents via Bcl-2 regulation. Cisplatin is an FDA-approved chemotherapeutic agent that still presents with acquired resistance in certain cervical cancer cases through p53 repression and Bcl-2 up-regulation, which is why there is ongoing research to understand the molecular mechanisms involved in the response of cervical cancer cells to Cisplatin. The present study, therefore, investigates the relationship between Cisplatin and RBBP6 gene expression in high-risk HPV-positive cervical cancer cells. RBBP6 was silenced in Hela, CaSki and Vero cells using RNAi technology, followed by measurement of wild-type p53 and Bcl-2 at mRNA level through RT-qPCR. Cells co-treated with Cisplatin and siRBBP6 were then analyzed for apoptosis induction and real time growth monitoring using flow cytometry and the xCELLigence system, respectively. Co-treated HeLa cells showed a reduction in apoptosis compared to the Cisplatin-only group despite complete repression of Bcl-2. Furthermore, real time cell monitoring revealed delayed growth inhibition in RBBP6-knockdown HeLa cells treated with Cisplatin, suggesting that RBBP6 is necessary for sensitizing HeLa cells to Cisplatin. Co-treated CaSki cells up-regulated wild-type p53 and down-regulated Bcl-2, and this was coupled with a higher percentage of apoptosis induction compared to the Cisplatin-only group. Cell growth analysis of CaSki cells also revealed delayed growth inhibition, but in the Cisplatin-only group where RBBP6 was highly expressed, suggesting that RBBP6 limits Cisplatin sensitivity in CaSki cells. Overall, our findings reveal that silencing RBBP6 enhances Cisplatin sensitivity in CaSki cells via Bcl-2 repression and p53 up-regulation, but absence of this gene desensitizes HeLa cells to Cisplatin and limits apoptosis induction and cell proliferation. This is the first study to reveal a possible relationship between RBBP6 and Cisplatin in HPV-positive cervical cancer cells. National Research Foundation (NRF): Grant Number 113980 South African Medical Research Council (SAMRC): Grant Number A1A979 Genetics MSc (Genetics) Unrestricted 2022-06-29T09:06:00Z 2022-06-29T09:06:00Z 2022-09 2022 Dissertation Mehta, H 2022, Probing the effects of Retinoblastoma Binding Protein 6 (RBBP6) knockdown on the sensitivity of cisplatin in cervical cancer cells, MSc Dissertation, University of Pretoria, Pretoria. S2022 https://repository.up.ac.za/handle/2263/86000 https://doi.org/10.25403/UPresearchdata.20132540 en © 2022 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 | RBBP6 p53 Bcl-2 Cisplatin Cervical Cancer UCTD Probing the effects of Retinoblastoma Binding Protein 6 (RBBP6) knockdown on the sensitivity of cisplatin in cervical cancer cells |
| title | Probing the effects of Retinoblastoma Binding Protein 6 (RBBP6) knockdown on the sensitivity of cisplatin in cervical cancer cells |
| title_full | Probing the effects of Retinoblastoma Binding Protein 6 (RBBP6) knockdown on the sensitivity of cisplatin in cervical cancer cells |
| title_fullStr | Probing the effects of Retinoblastoma Binding Protein 6 (RBBP6) knockdown on the sensitivity of cisplatin in cervical cancer cells |
| title_full_unstemmed | Probing the effects of Retinoblastoma Binding Protein 6 (RBBP6) knockdown on the sensitivity of cisplatin in cervical cancer cells |
| title_short | Probing the effects of Retinoblastoma Binding Protein 6 (RBBP6) knockdown on the sensitivity of cisplatin in cervical cancer cells |
| title_sort | probing the effects of retinoblastoma binding protein 6 rbbp6 knockdown on the sensitivity of cisplatin in cervical cancer cells |
| topic | RBBP6 p53 Bcl-2 Cisplatin Cervical Cancer UCTD |
| url | https://repository.up.ac.za/handle/2263/86000 https://doi.org/10.25403/UPresearchdata.20132540 |