title: Inhibition of cervical cancer cell growth in vitro and in vivo by lentiviral-vector mediated shRNA targeting the common promoter of HPV16 E6 and E7 oncogenes.
abstract: Deregulated expression of high-risk human papillomavirus oncogenes (E6 and E7) is a pivotal event for pathogenesis and progression in cervical cancer. Both viral oncogenes are therefore regarded as ideal therapeutic targets. Small interfering RNAs (siRNA) or double-stranded RNAs can knock down target genes effectively through siRNA-induced transcriptional gene silencing (TGS). Here, we established lentiviral-vector mediated shRNA (LV-shRNA) targeting common promoter of HPV16 E6/E7 and targeting E6 transcript, transduced the lentiviral construct into cervical HPV16-positive cell lines Siha and Caski, then selected and established stably transduced monoclonal cell lines. The results showed that LV-shRNA targeting promoter, as well as targeting E6 transcript, effectively knocked down E6 and E7 expression, resulted in accumulation of p53 and pRB protein and decrease of MCM7 and p16 protein, and consequently remarkably reduced the abilities of proliferation and invasiveness of cervical cancers cells in vitro. Then we inoculated subcutaneously those monoclonal cells into nude mice to establish the transplanted tumor animal models, and found dramatically inhibited tumorigenesis and growth, as well as prolonged survival time of mice incubated by cells with LV-shRNA targeting promoter and E6 transcript. Our results may provide evidence for application of LV-shRNA targeting HR-HPV key oncogenes, as a new treatment strategy, in cervical and other HPV-associated cancer therapy.
authors.affiliation: Women's Reproductive Health Laboratory of Zhejiang Province, China.
authors.forename: Jiansong
authors.initials: J
authors.lastname: Zhou
authors.forename: Baohua
authors.initials: B
authors.lastname: Li
authors.forename: Chanjuan
authors.initials: C
authors.lastname: Peng
authors.forename: Fenfen
authors.initials: F
authors.lastname: Wang
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Fu
authors.forename: Caiyun
authors.initials: C
authors.lastname: Zhou
authors.forename: Die
authors.initials: D
authors.lastname: Hong
authors.forename: Feng
authors.initials: F
authors.lastname: Ye
authors.forename: Weiguo
authors.initials: W
authors.lastname: Lü
authors.forename: Xing
authors.initials: X
authors.lastname: Xie
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D020868:Gene Silencing; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics / Q000502:physiology; D052162:Human papillomavirus 16 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016086:Lentivirus / Q000235:genetics / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D050725:Papillomavirus E7 Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000503:physiopathology / Q000628:therapy / Q000821:virology*
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16