Fig. 5: Inactivation of LATS2 and inhibition of TERT show a synthetic lethal phenotype, requiring RdDP activity of TERT.

A Each cell was transfected with siTERT. Cell viability was measured after 144 h of siTERT treatment using CCK-8. B The knockdown efficiency of TERT. mRNA was collected after 72 h of siTERT treatment. C The IC50 of the TERT inhibitors (BIBR1532, trichostatin, doxorubicin, TMPyP4, suramin, and VX222) in MeT-5A (WT, LATS1 KO, and LATS2 KO). The diluted TERT inhibitor was applied to each cell, and cell viability was measured after 144 h of incubation using CCK-8. D hTERT D712A- and hTERT T249A-overexpressing plasmids were transfected into HOMC-D4 (non-target [shNT] and LATS1/2 KD) and MeT-5A (WT and LATS2 KO) cells. The cell viability was measured after 144 h of transfection using CCK-8. All experiments were performed at least three independent times. Data are presented as means ± SD, and p values were calculated using the Tukey-Kramer method. * indicates p < 0.05, ** indicates p < 0.01 and *** indicates p < 0.001. n.s. - no significant difference.