REV3L, a promising target in regulating the chemosensitivity of cervical cancer cells

Li Yang1, Tingyan Shi2, Fei Liu3

  • 1Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Gynecologic Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.

Plos One
|March 18, 2015
PubMed

Insights

REV3L, a key DNA repair protein, is upregulated in cervical cancer and impacts cisplatin sensitivity. Targeting REV3L may improve chemotherapy effectiveness for cervical cancer patients.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • REV3L, the catalytic subunit of DNA Polymerase ζ (Polζ), is crucial for translesion synthesis (TLS), a DNA damage tolerance mechanism.
  • The role of REV3L in the chemosensitivity of cervical cancer remains underexplored.

Purpose of the Study:

  • To investigate the role of REV3L in cervical cancer cell proliferation, colony formation, and response to cisplatin treatment.
  • To evaluate the expression levels of Polζ protein in cervical cancer tissues.

Main Methods:

  • Immunohistochemistry was used to assess Polζ protein expression in cervical cancer and normal tissues.
  • Cervical cancer cell lines were engineered for REV3L suppression or overexpression.
  • Cell proliferation, colony formation, cell cycle progression, and apoptosis rates were analyzed.
  • Expression levels of key apoptosis-related proteins (Bcl-2, Mcl-1, Bcl-xl, Bax) were examined.

Main Results:

  • Polζ expression was significantly higher in cervical cancer tissues compared to normal tissues.
  • REV3L depletion inhibited cervical cancer cell proliferation and colony formation by inducing G1 arrest.
  • REV3L overexpression promoted cell proliferation and colony formation by facilitating G1 to S phase transition.
  • REV3L suppression enhanced sensitivity to cisplatin, while overexpression conferred resistance, altering apoptosis rates and related protein expression.

Conclusions:

  • REV3L plays a critical role in regulating cervical cancer cell proliferation and response to cisplatin.
  • Targeting REV3L presents a potential therapeutic strategy to modulate chemosensitivity in cervical cancer patients.

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