HIV-Tat-mediated Delivery of an LPTS Functional Fragment Inhibits Telomerase Activity and Tumorigenecity of Hepatoma Cells

Recently, Gastroenterology online released the latest research finding of Prof. Mujun Zhao from SIBCB: HIV-Tat–mediated Delivery of an LPTS Functional Fragment Inhibits Telomerase Activity and Tumorigenecity of Hepatoma Cells.

 

Human LPTS is a liver-related, putative tumor suppressor gene that encodes a telomerase inhibitory protein that is similar to human PinX1. The LPTS protein binds directly to the telomerase catalytic subunit (hTERT) and suppresses telomerase activity. Telomere maintenance and telomerase activity are required for long-term proliferation of cancer cells, so LPTS might be used in anti-cancer strategies. In Prof. Zhao’s study, the carboxy-terminal (functional) fragment of LPTS was fused to HIV Tat- an 11 amino acid peptide that translocates across the cell membrane; the fusion protein (TAT–LPTS-LC) was purified and transduced into cells. The researchers identified telomerase activity by using the telomeric repeat amplification protocol, and evaluated the effects of the TAT–LPTS-LC protein on cell proliferation and death by MTT and flow cytometry analyses. Tumor growth was also analyzed in nude mice. The results showed that the purified TAT–LPTS-LC protein was efficiently delivered into the cells, where it suppressed telomerase activity and shortened telomere length. TAT–LPTS-LC inhibited proliferation of telomerase-positive hepatocellular carcinoma BEL-7404 and hepatoblastoma HepG2cells and induced their death; however, it had no effects on telomerase-negative liver cell line L02 and osteosarcoma cell line Saos-2. The results suggest that TAT–LPTS-LC inhibits telomerase activity and could be used as an anti-cancer agent.

 

This research was supported by the Ministry of Science and Technology, National Natural Science Foundation of China, Shanghai Municipal Commission for Science and Technology.