[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.