MicroRNA-mediated epigenetic regulation of HDAC8 and HDAC6: Functional significance in cervical cancer
Debasmita Naik1, Arunasree M Kalle1
1Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana State, 500046, India.
Abstract:
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.
Insights
Two microRNAs, miR-497-3p and miR-324-3p, were identified as novel regulators of histone deacetylases (HDACs) in cervical cancer. Their elevated expression may inhibit cancer progression and metastasis.
Area of Science:
- Molecular Biology
- Oncology
- Epigenetics
Background:
- Cervical cancer is a major cause of female mortality with complex molecular drivers.
- Epigenetic regulators, including histone deacetylases (HDACs) and microRNAs (miRNAs), are implicated in cervical cancer progression.
- miRNAs are emerging as potential regulators of HDACs, offering therapeutic targets.
Purpose of the Study:
- To identify specific miRNAs that regulate HDAC8 and HDAC6 in cervical cancer cells.
- To investigate the functional consequences of miRNA-mediated regulation of HDACs.
Main Methods:
- In-silico miRNA prediction and computational analysis.
- Quantitative real-time PCR (qRT-PCR) for co-expression studies.
- Dual-Luciferase reporter assays to confirm miRNA-target interactions.
- Functional assays in HeLa cervical cancer cells.
Main Results:
- miR-497-3p was identified as a negative regulator of HDAC8, and miR-324-3p as a negative regulator of HDAC6.
- Overexpression of miR-497-3p increased acetylation of p53 and α-tubulin by suppressing HDAC8.
- Overexpression of miR-324-3p inhibited HDAC6, enhancing acetylation of Hsp90 and α-tubulin.
- Inhibition of HDAC8 via miRNA overexpression reduced cell viability, suppressed epithelial-to-mesenchymal transition (EMT), and promoted microtubule formation.
Conclusions:
- miR-497-3p and miR-324-3p are novel negative regulators of HDAC8 and HDAC6, respectively, in cervical cancer.
- These miRNAs demonstrate potential therapeutic value in targeting cervical cancer metastasis and progression.
- Targeted elevation of these miRNAs could offer a novel intervention strategy for cervical malignancy.
Related Concept Videos
01:46Epigenetic Regulation
01:22MicroRNAs
02:25Spreading of Chromatin Modifications
Writers
The writer...
02:23Master Transcription Regulators
02:32Histone Modification
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
02:30Histone Variants at the Centromere