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Suppression of CCDC6 sensitizes tumor to oncolytic virus M1

Ying Liu1, Ke Li2, Wen-Bo Zhu3

  • 1Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Guangzhou, China.

Neoplasia (New York, N.Y.)
|December 18, 2020
PubMed

Insights

Newly identified M1 virus shows promise in cancer treatment. Knocking down CCDC6 enhances M1 virus replication and ER stress-induced apoptosis, suggesting CCDC6 as a target to improve oncolytic virus therapy efficacy.

Area of Science:

  • Oncolytic virology
  • Cancer biology
  • Molecular mechanisms of viral therapy

Background:

  • Oncolytic viruses offer a promising cancer treatment strategy by selectively destroying cancer cells.
  • The innate antiviral defenses of cancer cells can limit the effectiveness of oncolytic virus therapy.
  • The molecular mechanisms behind the anticancer activity of the novel M1 oncolytic virus remain largely uncharacterized.

Purpose of the Study:

  • To elucidate the molecular mechanisms of the M1 oncolytic virus's anticancer activity.
  • To identify host factors influencing M1 virus efficacy.
  • To explore CCDC6 as a potential therapeutic target for enhancing oncolytic virotherapy.

Main Methods:

  • Cell viability assays (MTT) and RNA sequencing were employed to assess M1 virus effects.
  • Gene knockdown using small interfering RNAs (siRNAs) was performed for functional analysis.
  • Caspase activity assays, immunohistochemistry, and an orthotopic bladder cancer mouse model were utilized.

Main Results:

  • CCDC6 was identified as a crucial host factor in M1 virus-mediated oncolysis.
  • Knockdown of CCDC6 enhanced M1 virus replication and induced endoplasmic reticulum (ER) stress-mediated apoptosis.
  • These effects were observed both in vitro and in an in vivo orthotopic bladder cancer model.

Conclusions:

  • CCDC6 plays a significant role in the oncolytic activity of the M1 virus.
  • Targeting CCDC6 presents a novel strategy to potentiate oncolytic virus therapy.
  • This research identifies CCDC6 as a potential target for developing novel therapeutic compounds to improve cancer treatment outcomes.
Keywords:
CCDC6Interferon pathwayM1 virusOncolytic virus

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