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Exploring miR-142-3p in cervical cancer: Implications for treatment response
Thesis (PhD)--Stellenbosch University, 2026.
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| Format: | Thesis |
| Language: | English |
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Stellenbosch : Stellenbosch University
2026
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| _version_ | 1867613915939078144 |
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| access_status_str | Open Access |
| author | Van der Merwe, Michelle Pauline |
| author2 | Engelbrecht, Anna-Mart |
| author_browse | Engelbrecht, Anna-Mart Van der Merwe, Michelle Pauline |
| author_facet | Engelbrecht, Anna-Mart Van der Merwe, Michelle Pauline |
| author_sort | Van der Merwe, Michelle Pauline |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (PhD)--Stellenbosch University, 2026. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/135692 |
| institution | Stellenbosch University (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:43:44.261Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2026 |
| publishDateRange | 2026 |
| publishDateSort | 2026 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/135692 Exploring miR-142-3p in cervical cancer: Implications for treatment response Van der Merwe, Michelle Pauline Engelbrecht, Anna-Mart Myburgh, Kathy Garnis, Cathie Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences. Thesis (PhD)--Stellenbosch University, 2026. Van der Merwe, M. P. 2026. Exploring miR-142-3p in cervical cancer: Implications for treatment response. Unpublished doctoral dissertation. Stellenbosch: Stellenbosch University [online]. Available: https://scholar.sun.ac.za/items/6f8e51b5-ff66-4a45-b5f4-5c437a450fa7 Background: Cervical cancer remains a major global health burden, and treatment resistance, particularly to cisplatin, significantly limits therapeutic success. MicroRNAs (miRNAs) and extracellular vesicles (EVs) have emerged as important regulators of tumor behavior, with the potential to influence both treatment response and tumor-microenvironment interactions. miR-142-3p is widely recognized as a tumor-suppressive miRNA in several cancers; however, its functional role in cervical cancer, especially in the context of cisplatin treatment, remains poorly understood. This study aimed to investigate the tumor-suppressive effects of miR-142-3p overexpression in cervical cancer, its ability to modulate cisplatin sensitivity, and the contribution of cervical cancer-derived EVs, including those enriched with miR-142-3p, to angiogenesis. Methods: HeLa, SiHa, and ME-180 cervical cancer cell lines were stably transduced with a lentiviral miR-142-3p overexpression construct, and functional assays were performed to assess cisplatin sensitivity, cell viability, drug-resistance markers, epithelial-to-mesenchymal transition (EMT), and migration. Ex vivo expression of miR-142-3p was also assessed in EVs isolated from the plasma of cervical cancer patients and healthy controls using size-exclusion chromatography (SEC), followed by qPCR analysis. Furthermore, to assess angiogenesis in vitro, EVs isolated from conditioned media using ultracentrifugation were applied to endothelial cells, and tube-formation assays were conducted. EVs were obtained from both miR-142-3p-overexpressing cells and vector controls. Results: miR-142-3p overexpression modestly enhanced cisplatin sensitivity in HeLa, SiHa, and ME-180 cells at selected concentration. Across all three cell lines, miR-142-3p overexpression reduced baseline cell viability. Although miR-142-3p did not broadly alter classical drug-resistance markers, it notably inhibited the cisplatin-induced upregulation of BCRP/ABCG2 in HeLa cells, suggesting a role in mitigating cisplatin-associated resistance mechanisms. miR-142-3p also reduced cell migration and suppressed EMT features, effects that were amplified in the presence of cisplatin, demonstrated by decreased Slug and increased E-cadherin expression in selected models. Ex vivo analyses confirmed the presence of EV-associated miR-142-3p in both cervical cancer patients and healthy controls. In vitro, EVs isolated from cervical cancer cell lines significantly increased endothelial tube formation; however, angiogenesis occurred independently of miR-142-3p enrichment within EVs. Conclusion: Overall, miR-142-3p acts as a tumor suppressor in cervical cancer by reducing cell viability, migration, and EMT, while enhancing cisplatin responsiveness, particularly at lower doses. Its ability to inhibit cisplatin-induced BCRP/ABCG2 expression further suggests a role in mitigating treatment resistance. Although cervical cancer-derived EVs promoted angiogenesis, this effect occurred independently of miR-142-3p enrichment, indicating that miR-142-3p itself does not drive pro-angiogenic activity and therefore does not pose a risk of enhancing tumor vascularization. Together, these findings highlight miR-142-3p as a promising molecular target for improving therapeutic sensitivity in cervical cancer without adversely affecting angiogenic pathways. Doctoral 2026-04-08T07:19:11Z 2026-04-08T07:19:11Z 2026-03 Thesis https://scholar.sun.ac.za/handle/10019.1/135692 en Stellenbosch University 138 pages application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Van der Merwe, Michelle Pauline Exploring miR-142-3p in cervical cancer: Implications for treatment response |
| title | Exploring miR-142-3p in cervical cancer: Implications for treatment response |
| title_full | Exploring miR-142-3p in cervical cancer: Implications for treatment response |
| title_fullStr | Exploring miR-142-3p in cervical cancer: Implications for treatment response |
| title_full_unstemmed | Exploring miR-142-3p in cervical cancer: Implications for treatment response |
| title_short | Exploring miR-142-3p in cervical cancer: Implications for treatment response |
| title_sort | exploring mir 142 3p in cervical cancer implications for treatment response |
| url | https://scholar.sun.ac.za/handle/10019.1/135692 |
| work_keys_str_mv | AT vandermerwemichellepauline exploringmir1423pincervicalcancerimplicationsfortreatmentresponse |