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.

BMC Cancer
|July 15, 2022
PubMed

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.

Related Concept Videos

Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.8K
Molecular Factors Affecting Cell Division01:27

Molecular Factors Affecting Cell Division

Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit 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...
3.3K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.9K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.3K