Suppression of CCDC6 sensitizes tumor to oncolytic virus M1

Neoplasia: An International Journal for Oncology Research

Liang Peng¹  Ke Li²  Ying Liu³  Cheng Hu³  Hao Zhang⁴  Guang-mei Yan⁴  Jian-guang Qiu⁴  Jing Cai⁴  Yuan Lin⁴  Jian-kai Liang⁵  Xin-cheng Liu⁶  Wen-bo Zhu⁶  Wen-tao Huang⁶ 

[1] Collaborative Innovation Center for Cancer Medicine, Guangzhou, China;Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Guangzhou, China;Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;Department of Pharmacology, Sun Yat-sen University, Guangzhou, China;Department of Urology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;Department of Urology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;

关键词: Oncolytic virus;    M1 virus;    CCDC6;    Interferon pathway;   

DOI  :  

来源: DOAJ

【 摘 要 】

Oncolytic virus is an effective therapeutic strategy for cancer treatment, which exploits natural or manipulated viruses to selectively target and kill cancer cells. However, the innate antiviral system of cancer cells may resistant to the treatment of oncolytic virus. M1 virus is a newly identified oncolytic virus belonging to alphavirus species, but the molecular mechanisms underlying its anticancer activity are largely unknown. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. RNA seq analysis was used to analyze the gene alternation after M1 virus infection. Small interfering RNAs transfection for gene knockdown was used for gene functional tests. Caspase-3/7 activity was detected by Caspase-Glo Assay Systems. A mice model of orthotopic bladder tumor was established to determine the oncolytic effectiveness of the M1 virus. The expression of cleaved-Caspase 3 as well as Ki-67 in tumor cells were detected by immunohistochemical analysis. To further define the molecular factors involved in M1 virus-mediated biological function, we knocked down genes related to alphavirus’ activity and found that CCDC6 plays an important role in the oncolytic activity of M1 virus. Moreover, knocked down of CCDC6 augments the reproduction of M1 virus and resulted in endoplasmic reticulum (ER) stress-induced cell apoptosis in vitro as well as in vivo orthotopic bladder cancer model. Our research provides a rational new target for developing new compounds to promote the efficacy of oncolytic virus therapy.

【 授权许可】

Unknown