[shRNA-mediated downregulation of TERT inhibits melanoma in vitro and in vivo].

Objective

To investigate the anti-tumor effect of knockdown of telomerase reverse transcriptase (TERT) in melanoma and its potential clinical value.

Methods

Employed TERT knockdown strategy and evaluated the expression of target gene by Western blot analysis and RT-qPCR. The in vitro effects of TERT knockdown strategy were evaluated by cell proliferation, apoptosis, migration and invasion assays in A375 cells line, and the in vivo effects were evaluated via a xenografts mouse tumor model.

Results

Following TERT knockdown, a significant downregulation of both mRNA transcripts and protein expression were observed (P＜0.001). Knockdown of TERT inhibited the proliferation, migration, and invasion of melanoma cells in vitro, while enhancing apoptosis and inducing significant G0/G1 phase cell cycle arrest [The values for cell viability, number of invasive cells, 24-hour wound healing rate, apoptosis ratio, and G0/G1 phase ratio in the Con group were (100.00±6.51)%, (270.22±19.31) cells, (49.72±1.90)%, (7.13±0.36)%, and (46.69±0.45)%, respectively; in the Neg group, they were (95.80±5.33)%, (260.67±16.52) cells, (52.32±1.68)%, (7.23±0.70)%, and (47.48±0.15)%, respectively; and in the shRNA group, they were (60.80±5.29)%, (106.67±14.11) cells, (20.75±4.64)%, (12.76±0.48)%, and (59.77±0.64)%, respectively, all P＜0.05]. The results of subcutaneous tumorigenesis experiment in nude mice indicated that stably knockdown TERT in melanoma cells attenuated the tumorigenicity.

Conclusion

TERT silencing effectively suppresses melanoma progression and metastasis, demonstrating its potential as a novel therapeutic target for melanoma treatment.