CTSB Knockdown Inhibits Proliferation and Tumorigenesis in HL-60 Cells.
CTSB Knockdown Inhibits Proliferation and Tumorigenesis in HL-60 Cells.
复制标题
DOI：
10.7150/ijms.54206
复制
发表时间：
2021
影响因子：
3.6
通讯作者：
Zhang N
中科院分区：
文献类型：
--
作者：
Peng S;Yang Q;Li H;Pan Y;Wang J;Hu P;Zhang N
背景：组织蛋白酶B（CTSB）在实体瘤中的表达已被广泛研究，CTSB的表达上调与肿瘤的进展有关。但CTSB在成人白血病中的研究尚未见报道。方法：从AML患者和健康献血员外周血单个核细胞（PBMC）中提取总RNA。采用qRT-PCR检测CTSB的表达。分析CTSB表达与患者总生存期（OS）和无病生存期（DFS）的关系。通过逆转录病毒感染和嘌呤霉素筛选建立稳定的HL-60 CTSB-shRNA细胞系。CCK-8法检测细胞增殖。采用软琼脂法和裸鼠移植瘤模型分析成瘤能力。Western blot检测CTSB和细胞信号通路蛋白的表达。结果如下：CTSB mRNA在AML患者中的表达水平与健康对照相比上调（p<0.001），并且CTSB在M1、M2、M4和M5 AML样品中的表达显著高于健康对照。AML中CTSB表达与WBC计数相关（p=0.037）。CTSB高表达患者的OS相对较差（p=0.007），DFS较短（p=0.018）。CTSB表达水平可作为OS（p=0.011）和DFS（p=0.004）的独立预后因素。在HL-60细胞中敲低CTSB表达可抑制HL-60细胞的增殖和体内致瘤作用。进一步的研究表明，在HL-60细胞中敲低CTSB表达可以使AKT信号通路失活。结论：AML患者CTSB mRNA表达上调。CTSB过表达与AML患者的不良预后相关，可作为AML患者OS和DFS的独立预后因素。CTSB基因在HL-60细胞中的表达下调可抑制HL-60细胞的增殖和成瘤。其潜在机制可能是抑制AKT信号通路。
Background: Cathepsin B (CTSB) was well documented in solid tumors, up-regulated of CTSB expression is linked with progression of tumors. However, the study of CTSB in adult leukemia has not been reported. Methods: Total RNA was isolated from PBMC (peripheral blood mononuclear cell) of AML patients and healthy donors. qRT-PCR was performed to detect the expression of CTSB. The association of CTSB expression with the patients' overall survival (OS) and disease-free survival (DFS) were analyzed. Stable HL-60 CTSB-shRNA cell lines were established by retrovirus infection and puromycin selection. Cell proliferation was detected by CCK-8 analysis. Tumorigenesis ability was analyzed by soft agar and xenograft nude mice model. Western blot was performed to detect the expression of CTSB and the proteins of cell signaling pathway. Results: The mRNA expression level of CTSB was up-regulated in AML patients compared to healthy control (p<0.001), and CTSB expression was significantly higher in M1, M2, M4 and M5 AML samples than healthy control. The CTSB expression in AML was associated with WBC count (p=0.037). Patients with high CTSB expression had a relatively poor OS (p=0.007) and a shorter DFS (p=0.018). Moreover, the expression level of CTSB may act as an independent prognostic factor for both OS (p=0.011) and DFS (p=0.004). Knockdown CTSB expression in HL-60 cells could inhibit the cells' proliferation and tumorigeneses in vitro and in vivo. Further study showed knockdown CTSB expression in HL-60 cells could inactive the AKT signaling pathway. Conclusions: CTSB mRNA was upregulated in AML patients. CTSB overexpression was correlated with poor prognosis and may serve as an independent prognostic factor for both OS and DFS in AML patients. Knockdown CTSB expression in HL-60 cells could inhibit the cells' proliferation and tumorigenesis. The underlying mechanism may be the inhibition of the AKT signaling pathway.
登录
查看更多内容
肝细胞癌中组织蛋白酶B的过度表达预示着HCC患者的不良预后
影响因子：
37.3
作者：
Ruan J;Zheng H;Rong X;Rong X;Zhang J;Fang W;Zhao P;Luo R
通讯作者：
Luo R
组织蛋白酶B促进结直肠肿瘤发生，细胞侵袭和转移。
影响因子：
4.6
作者：
Bian B;Mongrain S;Cagnol S;Langlois MJ;Boulanger J;Bernatchez G;Carrier JC;Boudreau F;Rivard N
通讯作者：
Rivard N
影响因子：
4.7
作者：
Wendt, Wiebke;Schulten, Roxane;Luebbert, Hermann
通讯作者：
Luebbert, Hermann
影响因子：
3.4
作者：
Cartledge, Donna M.;Colella, Rita;Glazewski, Lisa;Lu, Guizhen;Mason, Robert W.
通讯作者：
Mason, Robert W.
影响因子：
4
作者：
Pu, Jing;Guardia, Carlos M.;Bonifacino, Juan S.
通讯作者：
Bonifacino, Juan S.