SETD2 inhibited T-cell acute lymphocytic leukemia invasion and infiltration by inhibiting the JAK/STAT pathway.

T-cell acute lymphocytic leukemia (T-ALL) is a malignant transformation of immature precursor T-cells that is highly aggressive. The disruption of SETD2 is thought to be a unique epigenetic mechanism for leukemia. This study aimed to investigate the role and possible mechanism of SETD2 in T-ALL. The expression of SETD2 in T-ALL tissues and cells was detected by RT-PCR, and siRNA (si-NC/si-SETD2) and overexpressed plasmids (ov-NC/ov-SETD2) were used to transfected T-ALL cell lines JURKAT and MOLT-4, and cell proliferation, migration/invasion and cell cycle were detected by CCK8, Transwell, flow cytometry, respectively. WB was used to detect the changes in the JAK/STAT pathway. The JAK/STAT inhibitor AG490 was further used to demonstrate the role of JAK/STAT in SETD2 regulation of T-ALL. Then, the effects of SETD2 on T-ALL tissue infiltration were verified in vivo. Results showed that SETD2 was significantly lowly expressed in T-ALL, and si-SETD2 promoted the proliferation, migration, invasion, cell cycle, and activation of the JAK/STAT pathway of T-ALL cells, while overexpression of SETD2 showed the opposite inhibitory effect. The use of AG490 inhibited the promoting effect of si-SETD2 on T-ALL, suggesting that JAK/STAT was involved in the regulation of SETD2 on T-ALL. In vivo experiments further confirmed that silencing SETD2 decreased the body weight of mice and increased the infiltration of JURKAT cells in the liver, kidney, spleen, lung, and brain, while overexpression of SETD2 showed inhibitory effects. In conclusion, SETD2 played an important role in T-ALL by inhibiting the JAK/STAT pathway to inhibit T-ALL proliferation, invasion, and transfection.