Semaphorin 4D is a potential biomarker in pediatric leukemia and promotes leukemogenesis by activating PI3K/AKT and ERK signaling pathways.
Semaphorin 4D is a potential biomarker in pediatric leukemia and promotes leukemogenesis by activating PI3K/AKT and ERK signaling pathways.
复制标题
DOI：
10.3892/or.2021.7952
复制
发表时间：
2021-04
期刊：
影响因子：
4.2
通讯作者：
Sun Q
中科院分区：
文献类型：
--
作者：
Jiang H;Tang J;Qiu L;Zhang Z;Shi S;Xue L;Kui L;Huang T;Nan W;Zhou B;Zhao C;Yu M;Sun Q
Semaphorin 4D（Sema 4D）在多种肿瘤中高度表达，并且与高侵袭性、不良预后和不良治疗反应相关。然而，Sema 4D在白血病中的表达和作用仍不清楚。本研究探讨Sema 4D在儿童白血病中的表达及其对白血病细胞的影响。结果表明，Sema 4D蛋白在儿童白血病患者外周血单个核细胞中高度表达，并且在这些患者的血浆中也观察到高水平的可溶性Sema 4D。Sema 4D基因敲低可使BALL-1细胞周期阻滞于G 0/G1期，抑制细胞增殖，促进细胞凋亡，而Sema 4D基因过表达则相反。在Jurkat细胞中，Sema 4D敲低抑制增殖并促进凋亡，而Sema 4D过表达降低了细胞周期G 0/G1期的细胞丰度并促进增殖。Sema 4D过表达也增加了Jurkat细胞的迁移能力和BALL-1细胞的侵袭能力。在Sema 4D敲低的Jurkat和BALL-1细胞中PI 3 K磷酸化水平均降低，而在Sema 4D敲低的BALL-1细胞中ERK磷酸化水平降低。PI 3 K、ERK和AKT的磷酸化水平在儿童白血病患者中升高，并且与Sema 4D表达的增加相关。Sema 4D过表达与急性髓性白血病患者的总生存期较短相关。本研究结果提示Sema 4D通过激活PI 3 K/AKT和ERK信号通路在白血病的发生发展中发挥重要作用，可能成为白血病诊断和治疗的潜在靶点。
Semaphorin 4D (Sema4D) is highly expressed in a variety of tumors and is associated with high invasion, poor prognosis and poor therapeutic response. However, the expression and role of Sema4D in leukemia remains unclear. The present study investigated the expression of Sema4D in pediatric leukemia and its effects in leukemia cells. The results demonstrated that Sema4D protein was highly expressed in peripheral blood mononuclear cells of patients with pediatric leukemia, and high levels of soluble Sema4D were also observed in the plasma of these patients. Sema4D knockdown induced cell cycle arrest in G0/G1 phase, inhibited proliferation and promoted apoptosis in BALL-1 cells, while Sema4D overexpression exhibited the opposite effect. In Jurkat cells, Sema4D knockdown inhibited proliferation and promoted apoptosis, while Sema4D overexpression decreased the abundance of the cells in the G0/G1 phase of the cell cycle and promoted proliferation. Sema4D overexpression also increased the migratory capacity of Jurkat cells and the invasive capacity of BALL-1 cells. The phosphorylation level of PI3K was decreased in both Sema4D knocked-down Jurkat and BALL-1 cells, and the phosphorylation level of ERK was decreased in Sema4D knocked-down BALL-1 cells. The phosphorylation levels of PI3K, ERK and AKT were elevated in patients with pediatric leukemia, and were correlated to the increased Sema4D expression. Sema4D overexpression was associated with a shorter overall survival in patients with acute myeloid leukemia. Overall, the results of the present study indicated that Sema4D serves an important role in leukemia development by activating PI3K/AKT and ERK signaling, and it may be used as a potential target for the diagnosis and treatment of leukemia.