Related Experiment Video
Updated: Sep 4, 2025

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
miR-34a negatively regulates cell cycle factor Cdt2/DTL in HPV infected cervical cancer cells
Garima Singh1, Sonika Kumari Sharma1, Samarendra Kumar Singh2
1Cell Cycle and Cancer Laboratory, School of Biotechnology, Institute of Science, Banaras Hindu University, Varanasi, UP-221005, India.
Abstract:
MicroRNAs have emerged as an important regulator of cell cycle and various other cellular processes. Aberration in microRNAs has been linked with development of several cancers and other diseases but still very little is known about the mechanism by which they regulate these cellular events. High risk human papilloma virus (HR HPV) is the causative agent of 99% of cervical cancer cases which attenuates multiple tumor suppressors and checkpoint factors of the host cell. The viral proteins also stabilize many oncogenic factors, including an essential cell cycle regulator Cdt2/DTL which in turn promotes cell transformation and proliferation. In this study, we report that a micro-RNA, miR-34a by suppressing HPV E6 protein, destabilizes Cdt2/DTL protein level in HPV infected cervical cancer cell lines. Destabilization of Cdt2 stabilizes pro-apoptotic and onco-suppressor proteins like p21 and Set8 and suppresses cell proliferation, invasion and migration capabilities of the HPV positive cervical cancer cells. Overexpression of either HPV E6 or Cdt2 genes along with miR-34a restored back the suppressed proliferation rate. This study is the first-ever report to show that miR-34a regulates cell cycle factor Cdt2 by suppressing viral E6 protein level, thus opening up the possibility of exploring miR-34a as a specific therapy for cervical cancer treatment.
Insights
MicroRNA miR-34a suppresses human papillomavirus E6 protein, destabilizing Cdt2 and inhibiting cervical cancer cell growth. This finding suggests miR-34a as a potential therapy for cervical cancer.
Area of Science:
- Molecular Biology
- Oncology
- Virology
Background:
- MicroRNAs regulate cellular processes, and their dysregulation is linked to cancer.
- High-risk human papillomavirus (HR HPV) drives cervical cancer by targeting tumor suppressors and stabilizing oncogenic factors like Cdt2/DTL.
- The precise mechanisms of microRNA-mediated regulation in HPV-infected cells are not fully understood.
Purpose of the Study:
- To investigate the role of miR-34a in regulating cell cycle factors in HPV-infected cervical cancer cells.
- To elucidate the mechanism by which miR-34a affects Cdt2/DTL protein levels and subsequent cellular events.
Main Methods:
- Utilized HPV-infected cervical cancer cell lines.
- Assessed the effect of miR-34a on HPV E6 protein levels.
- Quantified Cdt2/DTL protein stability and levels of associated proteins (p21, Set8).
- Evaluated the impact on cell proliferation, invasion, and migration.
Main Results:
- miR-34a was found to suppress HPV E6 protein.
- Suppression of E6 by miR-34a led to Cdt2/DTL destabilization.
- Cdt2 destabilization resulted in increased p21 and Set8 levels, inhibiting cell proliferation, invasion, and migration.
- Overexpression of HPV E6 or Cdt2 reversed the suppressive effects of miR-34a.
Conclusions:
- miR-34a regulates the cell cycle factor Cdt2 by suppressing the viral HPV E6 protein.
- This mechanism highlights a novel pathway for controlling HPV-driven cervical cancer.
- miR-34a presents a promising therapeutic target for cervical cancer treatment.
More Related Videos
Related Concept Videos
Negative Regulator Molecules
Molecular Factors Affecting Cell Division
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Inhibition of Cdk Activity
Abnormal Proliferation
DNA Damage can Stall the Cell Cycle
Positive Regulator Molecules

