MicroRNA-mediated epigenetic regulation of HDAC8 and HDAC6: Functional significance in cervical cancer
Cervical cancer, a leading global cause of female mortality, exhibits diverse molecular aberrations influencing gene expression and signaling pathways. Epigenetic factors, including histone deacetylases (HDACs) such as HDAC8 and HDAC6, along with microRNAs (miRNAs), play pivotal roles in cervical ca...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2024-09-01
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| Series: | Non-coding RNA Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468054024000301 |
| _version_ | 1797232788151205888 |
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| author | Debasmita Naik Arunasree M. Kalle |
| author_facet | Debasmita Naik Arunasree M. Kalle |
| author_sort | Debasmita Naik |
| collection | DOAJ |
| description | Cervical cancer, a leading global cause of female mortality, exhibits diverse molecular aberrations influencing gene expression and signaling pathways. Epigenetic factors, including histone deacetylases (HDACs) such as HDAC8 and HDAC6, along with microRNAs (miRNAs), play pivotal roles in cervical cancer progression. Recent investigations have unveiled miRNAs as potential regulators of HDACs, offering a promising therapeutic avenue. This study employed in-silico miRNA prediction, qRT-PCR co-expression studies, and Dual-Luciferase reporter assays to identify miRNAs governing HDAC8 and HDAC6 in HeLa, cervical cancer cells. Results pinpointed miR-497–3p and miR-324–3p as novel negative regulators of HDAC8 and HDAC6, respectively. Functional assays demonstrated that miR-497–3p overexpression in HeLa cells suppressed HDAC8, leading to increased acetylation of downstream targets p53 and α-tubulin. Similarly, miR-324–3p overexpression inhibited HDAC6 mRNA and protein expression, enhancing acetylation of Hsp90 and α-tubulin. Notably, inhibiting HDAC8 via miRNA overexpression correlated with reduced cell viability, diminished epithelial-to-mesenchymal transition (EMT), and increased microtubule bundle formation in HeLa cells. In conclusion, miR-497–3p and miR-324–3p emerge as novel negative regulators of HDAC8 and HDAC6, respectively, with potential therapeutic implications. Elevated expression of these miRNAs in cervical cancer cells holds promise for inhibiting metastasis, offering a targeted approach for intervention in cervical malignancy. |
| first_indexed | 2024-04-24T16:05:50Z |
| format | Article |
| id | doaj.art-0bad0d41f1d3492fbedfcc02058dd15e |
| institution | Directory Open Access Journal |
| issn | 2468-0540 |
| language | English |
| last_indexed | 2024-04-24T16:05:50Z |
| publishDate | 2024-09-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Non-coding RNA Research |
| spelling | doaj.art-0bad0d41f1d3492fbedfcc02058dd15e2024-04-01T04:04:25ZengKeAi Communications Co., Ltd.Non-coding RNA Research2468-05402024-09-0193732743MicroRNA-mediated epigenetic regulation of HDAC8 and HDAC6: Functional significance in cervical cancerDebasmita Naik0Arunasree M. Kalle1Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana State, 500046, IndiaCorresponding author.; Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana State, 500046, IndiaCervical cancer, a leading global cause of female mortality, exhibits diverse molecular aberrations influencing gene expression and signaling pathways. Epigenetic factors, including histone deacetylases (HDACs) such as HDAC8 and HDAC6, along with microRNAs (miRNAs), play pivotal roles in cervical cancer progression. Recent investigations have unveiled miRNAs as potential regulators of HDACs, offering a promising therapeutic avenue. This study employed in-silico miRNA prediction, qRT-PCR co-expression studies, and Dual-Luciferase reporter assays to identify miRNAs governing HDAC8 and HDAC6 in HeLa, cervical cancer cells. Results pinpointed miR-497–3p and miR-324–3p as novel negative regulators of HDAC8 and HDAC6, respectively. Functional assays demonstrated that miR-497–3p overexpression in HeLa cells suppressed HDAC8, leading to increased acetylation of downstream targets p53 and α-tubulin. Similarly, miR-324–3p overexpression inhibited HDAC6 mRNA and protein expression, enhancing acetylation of Hsp90 and α-tubulin. Notably, inhibiting HDAC8 via miRNA overexpression correlated with reduced cell viability, diminished epithelial-to-mesenchymal transition (EMT), and increased microtubule bundle formation in HeLa cells. In conclusion, miR-497–3p and miR-324–3p emerge as novel negative regulators of HDAC8 and HDAC6, respectively, with potential therapeutic implications. Elevated expression of these miRNAs in cervical cancer cells holds promise for inhibiting metastasis, offering a targeted approach for intervention in cervical malignancy.http://www.sciencedirect.com/science/article/pii/S2468054024000301HDAC8HDAC6MiRNAMiR-324–3pMiR-497–3pCervical cancer |
| spellingShingle | Debasmita Naik Arunasree M. Kalle MicroRNA-mediated epigenetic regulation of HDAC8 and HDAC6: Functional significance in cervical cancer Non-coding RNA Research HDAC8 HDAC6 MiRNA MiR-324–3p MiR-497–3p Cervical cancer |
| title | MicroRNA-mediated epigenetic regulation of HDAC8 and HDAC6: Functional significance in cervical cancer |
| title_full | MicroRNA-mediated epigenetic regulation of HDAC8 and HDAC6: Functional significance in cervical cancer |
| title_fullStr | MicroRNA-mediated epigenetic regulation of HDAC8 and HDAC6: Functional significance in cervical cancer |
| title_full_unstemmed | MicroRNA-mediated epigenetic regulation of HDAC8 and HDAC6: Functional significance in cervical cancer |
| title_short | MicroRNA-mediated epigenetic regulation of HDAC8 and HDAC6: Functional significance in cervical cancer |
| title_sort | microrna mediated epigenetic regulation of hdac8 and hdac6 functional significance in cervical cancer |
| topic | HDAC8 HDAC6 MiRNA MiR-324–3p MiR-497–3p Cervical cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2468054024000301 |
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