Inhibition of proliferation and induction of apoptosis in human renal carcinoma cells by anti-telomerase small interfering RNAs.
Telomerase is an attractive molecular target for cancer therapy because it is present in most malignant cells but is undetectable in most normal somatic cells. Human telomerase consists of two subunits, an RNA component (hTR) and a human telomerase reverse transcriptase component (hTERT). Small interfering RNA (siRNA), one kind of RNA interferences, has been demonstrated to be an effective method to inhibit target gene expression in human cells. We investigated the effects of siRNA targeting at both hTR and hTERT mRNA on the inhibition of telomerase activity in human renal carcinoma cells (HRCCs). The proliferation and apoptosis of HRCCs were examined. The treatment of HRCCs using hTR and hTERT siRNAs resulted in significant decrease of hTR mRNA, hTERT mRNA and hTERT protein. The siRNA can also inhibit the telomerase activity and the proliferation of HRCCs. Moreover, they can induce apoptotic cell death in a dose-dependent manner. From these findings, we propose that the inhibition of telomerase activity using siRNA targeting hTR and hTERT might be a rational approach in renal cancer therapy.
Zheng
Jun-Nian
JN
Laboratory of Urology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China. jnzheng@xzmc.edu.cn
Sun
Ya-Feng
YF
Pei
Dong-Sheng
DS
Liu
Jun-Jie
JJ
Chen
Jia-Cun
JC
Li
Wang
W
Sun
Xiao-Qing
XQ
Shi
Qi-Duo
QD
Han
Rui-Fa
RF
Ma
Teng-Xiang
TX
D017209:Apoptosis; D002292:Carcinoma, Renal Cell / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D012313:RNA / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase