PMID- 18060502
OWN - NLM
STAT- MEDLINE
DCOM- 20080603
LR  - 20101118
IS  - 1360-8185 (Print)
IS  - 1360-8185 (Linking)
VI  - 13
IP  - 2
DP  - 2008 Feb
TI  - RNA interference against HPV16 E7 oncogene leads to viral E6 and E7 suppression 
      in cervical cancer cells and apoptosis via upregulation of Rb and p53.
PG  - 273-81
AB  - The simultaneous expression of human papillomavirus type 16 (HPV16) E6 and E7 
      oncogenes is pivotal for malignant transformation and maintenance of malignant 
      phenotypes. Silencing these oncogenes is considered to be applicable in molecular 
      therapies of human cervical cancer. However, it remains to be determined whether 
      HPV16 E6 and E7 could be both silenced to obtain most efficient antitumor 
      activity by using RNA interference (RNAi) technology. Herein, we designed a small 
      interfering RNA (siRNA) targeting HPV16-E7 region to degrade either E6, or 
      truncated E6 (E6*) and E7 mRNAs and to simultaneously knockdown both E6 and E7 
      expression. Firstly, the sequence targeting HPV16-E7 region was inserted into the 
      shRNA packing vector pSIREN-DNR, yielding pSIREN-16E7 to stably express 
      corresponding shRNA. HPV16-transformed SiHa and CaSki cells were used as a model 
      system; RT-PCR, Western Blotting, MTT assay, TUNEL staining, Annexin V apoptosis 
      assay and flow cytometry were applied to examine the effects of pSIREN-16E7. Our 
      results indicated that HPV16-E7 specific shRNA (16E7-shRNA) induced selective 
      degradation of E6 and E7 mRNAs and proteins. E6 silencing induced accumulation of 
      cellular p53 and p21. In contrast, E7 silencing induced hypophosphorylation of 
      retinoblastoma (Rb) protein. The loss of E6 and E7 reduced cell growth and 
      ultimately resulted in massive apoptotic cell death selectively in HPV-positive 
      cancer cells, compared with the HPV-negative ones. We demonstrated that 
      16E7-shRNA can induce simultaneous E6 and E7 suppression and lead to striking 
      apoptosis in HPV16-related cancer cells by activating cellular p53, p21 and Rb. 
      Therefore, RNAi using E7 shRNA may have the gene-specific therapy potential for 
      HPV16-related cancers.
FAU - Sima, Ni
AU  - Sima N
AD  - Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, 1095 Jiefang Ave., Wuhan, Hubei 430030, PR 
      China.
FAU - Wang, Wei
AU  - Wang W
FAU - Kong, Debo
AU  - Kong D
FAU - Deng, Dongrui
AU  - Deng D
FAU - Xu, Qian
AU  - Xu Q
FAU - Zhou, Jianfeng
AU  - Zhou J
FAU - Xu, Gang
AU  - Xu G
FAU - Meng, Li
AU  - Meng L
FAU - Lu, Yunping
AU  - Lu Y
FAU - Wang, Shixuan
AU  - Wang S
FAU - Ma, Ding
AU  - Ma D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Apoptosis
JT  - Apoptosis : an international journal on programmed cell death
JID - 9712129
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (E6 protein, Human papillomavirus type 16)
RN  - 0 (Oncogene Proteins, Viral)
RN  - 0 (Papillomavirus E7 Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (oncogene protein E7, Human papillomavirus type 16)
SB  - IM
MH  - *Apoptosis
MH  - Cyclin-Dependent Kinase Inhibitor p21/metabolism
MH  - Female
MH  - Genes, Viral
MH  - Human papillomavirus 16/genetics
MH  - Humans
MH  - Oncogene Proteins, Viral/*genetics/metabolism
MH  - Oncogenes
MH  - Papillomavirus E7 Proteins
MH  - *RNA Interference
MH  - Repressor Proteins/*genetics/metabolism
MH  - Retinoblastoma Protein/*metabolism
MH  - Tumor Suppressor Protein p53/*metabolism
MH  - Up-Regulation
MH  - Uterine Cervical Neoplasms/metabolism/*pathology/virology
EDAT- 2007/12/07 09:00
MHDA- 2008/06/05 09:00
CRDT- 2007/12/07 09:00
PHST- 2007/12/07 09:00 [pubmed]
PHST- 2008/06/05 09:00 [medline]
PHST- 2007/12/07 09:00 [entrez]
AID - 10.1007/s10495-007-0163-8 [doi]
PST - ppublish
SO  - Apoptosis. 2008 Feb;13(2):273-81. doi: 10.1007/s10495-007-0163-8.