Abstract
BackgroundTelomerase plays an important role in cell proliferation and carcinogenesis and is believed to be a good target for anti-cancer drugs. Elimination of template function of telomerase RNA may repress the telomerase activity.MethodsA pseudo-knotted HDV ribozyme (g.RZ57) directed against the RNA component of human telomerase (hTR) was designed and synthesized. An in vitro transcription plasmid and a eukaryotic expression plasmid of ribozyme were constructed. The eukaryotic expression plasmid was induced into heptocellular carcinoma 7402 cells, colon cancer HCT116 cells and L02 hepatocytes respectively. Then we determine the cleavage activity of ribozyme against human telomerase RNA component (hTR) both in vitro and in vivo, and detect telomerase activity continuously.ResultsHDV ribozyme showed a specific cleavage activity against the telomerase RNA in vitro. The maximum cleavage ratio reached about 70.4%. Transfection of HDV ribozyme into 7402 cells and colon cancer cells HCT116 led to growth arrest and the spontaneous apoptosis of cells, and the telomerase activity dropped to 10% of that before.ConclussionHDV ribozyme (g.RZ57) is an effective strategy for gene therapy.
Highlights
Telomerase plays an important role in cell proliferation and carcinogenesis and is believed to be a good target for anti-cancer drugs
Immortalized and malignant tumor cells are characterized by unlimited cell proliferation and programmed cell death
Autexier [22]et al have proved that the functional area is located between 44 to 203 nt, in the experiment we cleave the template region located from 47 to 50 nt on Human telomerase RNA (hTR), and it should cause the significant reduction in telomerase activity
Summary
Telomerase plays an important role in cell proliferation and carcinogenesis and is believed to be a good target for anti-cancer drugs. Elimination of template function of telomerase RNA may repress the telomerase activity. Immortalized and malignant tumor cells are characterized by unlimited cell proliferation and programmed cell death (apoptosis). Telomerase activity is found in almost all malignant tumors [3]. Human telomerase RNA (hTR) is associated with the activity of telomerase, immortalized cancer cells retain the highest level of hTR [4,5]. Hammerhead ribozymes were used to inhibit the telomerase activity by targeting the template region of telomerase RNA in malignant tumors [6,7]. There is no report about HDV ribozyme for inhibition of telomerase activity
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