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已发表论文

人类宫颈癌细胞中成簇规律间隔短回文重复序列/Cas 系统对人乳头瘤病毒 16 E6  基因的中断

 

Authors Yu L, Wang XL, Zhu D, Ding WC, Wang LM, Zhang CL, Jiang XH, Shen H, Liao SJ, Ma D, Hu Z, Wang H

Published Date December 2014 Volume 2015:8 Pages 37—44

DOI http://dx.doi.org/10.2147/OTT.S64092

Received 14 March 2014, Accepted 9 June 2014, Published 22 December 2014

Abstract: High-risk human papillomavirus (HPV), especially HPV16, is considered a main causative agent of cervical cancer. Upon HPV infection, the viral oncoprotein E6 disrupts the host tumor-suppressor protein p53, thus promoting malignant transformation of normal cervical cells. Here, we used the newly developed programmable ribonucleic acid-guided clustered regularly interspaced short palindromic repeat (CRISPR)/Cas system to disrupt the HPV16 E6  gene. We showed that HPV16 E6  deoxyribonucleic acid was cleaved at specific sites, leading to apoptosis and growth inhibition of HPV16-positive SiHa and CaSki cells, but not HPV-negative C33A or human embryonic kidney 293 cells. We also observed downregulation of the E6 protein and restoration of the p53 protein. These data proved that the HPV16 E6 ribonucleic acid-guided CRISPR/Cas system might be an effective therapeutic agent in treating HPV infection-related cervical malignancy.
Keywords: CRISPR/Cas system, E6, p53, SiHa, CaSki, cervical cancer







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