To delineate the extra telomeric function of hTERT, loss of gene expression
studies was carried out. Knockdown of hTERT using siRNA
and shRNA lowered the hTERT transcript as well as telomerase activity
and altered the global gene expression in cancer cells.Microarray studies
revealed that expression of certain annotated genes gets altered
upon knockdown; 80 geneswere upregulated and 73 genes downregulated
by both agents. Among genes with known role in cancer, 25 were
upregulated and 12 genes downregulated. Real Time PCR showed that
four genes viz., KLF4, FGF2, PLAU and IRF9, seemingly important for cancer
progression, were upregulated upon knockdown of hTERT. Among
them KLF4 and FGF2 are known to be activator of hTERT expression,
reflecting a possible feed-back loop mediated autoregulation of expression
of hTERT. The finding provides further insight in to the potential
role of hTERT in cellular physiology in functions other than telomere
lengthening.