Inhibition of telomerase activity in cancer cells using short hairpin RNA expression vectors.
Telomerase activity is mainly regulated by the human telomerase reverse transcriptase (hTERT) gene. Our objective was to investigate the effect of short hairpin RNA (shRNA) directed against hTERT mRNA on telomerase activity in laryngeal cancer cells (Hep-2), nasopharyngeal carcinoma cells (NEC), and human bone marrow mesenchyme stem cells (hMSCs). Short hairpin RNA expression vectors targeting the messenger RNA of hTERT were constructed. Cells were treated with shRNA expression vectors directed against hTERT mRNA and control vectors that included mismatched shRNA. We found that treatment of special shRNA expression vectors induced significantly decrease in hTERT expression, telomerase activity, and cell viability in Hep-2 and NEC cells. In contrast, the shRNA control showed none of these effects. And none of these effects appeared in hMSCs cells. Our results suggest that shRNA against hTERT mRNA inhibits telomerase activity and cell viability through suppression of the hTERT expression in cancer cells. And this treatment has no side effect on healthy cells lack of telomerase activity. RNA interfering technology may be a promising strategy for the treatment of cancers.
Chen
Shi-Ming
SM
Department of Otolaryngology-Head & Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. shimingchen0468@hotmail.com
Tao
Ze-Zhang
ZZ
Hua
Qing-Quan
QQ
Xiao
Bo-Kui
BK
Xu
Yu
Y
Wang
Yan
Y
Deng
Yu-Qin
YQ
D045744:Cell Line, Tumor; D002470:Cell Survival; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000201:enzymology / Q000628:therapy*; D010957:Plasmids; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use*; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D012333:RNA, Messenger; D034741:RNA, Small Interfering; C509186:TERT protein, human; D019098:Telomerase