[Inhibiting expression of human telomerase reverse transcriptase promotes degradation of survivin protein]

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Survivin and human telomerase reverse transcriptase (hTERT) expression correlate in cancer cells.
• Both Survivin and hTERT are potential targets for cancer gene therapy.

Purpose of the Study:

• To investigate the regulatory relationship between Survivin and hTERT in cancer cells.
• To determine if hTERT influences Survivin expression or stability.

Main Methods:

• Used antisense oligonucleotides to inhibit Survivin and hTERT expression in HeLa S3 cells.
• Assessed telomerase activity using the telomerase repeat amplification (TRAP) assay.
• Analyzed protein and mRNA levels of Survivin via Western blot and RT-PCR, respectively.
• Evaluated cell proliferation using the MTT assay.

Main Results:

• Inhibiting Survivin expression did not affect telomerase activity.
• Inhibiting hTERT expression reduced Survivin protein levels in a dose-dependent manner, without altering mRNA levels.
• The reduction in Survivin protein was mitigated by proteasome inhibitors (lactacystin, MG132), indicating proteasomal degradation.
• Simultaneous inhibition of hTERT and Survivin synergistically reduced cancer cell proliferation.

Conclusions:

• Inhibition of hTERT in HeLa S3 cells enhances the ubiquitin-proteasome degradation pathway for Survivin.
• hTERT plays a role in regulating Survivin protein stability, independent of mRNA levels.
• Targeting hTERT may be a strategy to reduce Survivin levels and inhibit cancer cell growth.