Department of Hematology, Yunnan Research Center of Hematology, the First Affiliated Hospital of Kunming Medical University, Kunming, P. R. China.
Department of Laboratory Medicine, Yuhuangding Hospital of Qingdao University, Yantai, P. R. China.
Cell Biol Int. 2018 Sep;42(9):1192-1199. doi: 10.1002/cbin.10989. Epub 2018 Jun 20.
Tripartite motif-containing 22 (TRIM22) is reported to participate in numerous cellular activities. Recent studies confirm that TRIM22 is a target gene for P53, and inhibits clonogenic growth of leukemic U-937 cells. The current study aims to discover the effect of TRIM22 in progression of human chronic myeloid leukemia (CML) and explore the related mechanism. TRIM22 was knocked down by siRNA transfection in CML cell K562. We observed that TRIM22 knockdown decreased proliferation and invasion in K562 cells. TRIM22 knockdown significantly induced cell cycle arrest by regulating the level of CDK4, Cyclin D1, P70S6K, and P53 in K562 cell. Moreover, loss of TRIM22 also promoted apoptosis through modulation of Bcl-2, Bax and active Caspase 3 in K562 cell. Furthermore, we demonstrated that TRIM22 knockdown inhibited the activation of PI3K/Akt/mTOR pathway by decreasing the level of the phosphorylated form p-Akt and p-mTOR in K562 cell. In conclusion, loss of TRIM22 suppresses the progression and invasion of CML through regulation of PI3K/Akt/mTOR pathway, suggesting that TRIM22 might be as a potential target for the treatment strategy of CML.
三结构域蛋白 22(TRIM22)被报道参与许多细胞活动。最近的研究证实,TRIM22 是 P53 的靶基因,并抑制白血病 U-937 细胞的集落形成生长。本研究旨在探讨 TRIM22 在人慢性髓系白血病(CML)进展中的作用及其相关机制。通过 siRNA 转染在 CML 细胞系 K562 中敲低 TRIM22。我们观察到 TRIM22 敲低可降低 K562 细胞的增殖和侵袭。TRIM22 敲低通过调节 CDK4、Cyclin D1、P70S6K 和 P53 的水平,显著诱导 K562 细胞的细胞周期停滞。此外,TRIM22 的缺失还通过调节 Bcl-2、Bax 和活性 Caspase 3 促进 K562 细胞的凋亡。此外,我们证明 TRIM22 敲低通过降低 K562 细胞中磷酸化形式 p-Akt 和 p-mTOR 的水平,抑制 PI3K/Akt/mTOR 通路的激活。总之,TRIM22 的缺失通过调节 PI3K/Akt/mTOR 通路抑制 CML 的进展和侵袭,提示 TRIM22 可能成为 CML 治疗策略的潜在靶点。