Int J Med Sci 2021; 18(6):1484-1491. doi:10.7150/ijms.54206 This issue
1. Department of Hematology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, China.
2. Department of Clinical Laboratory, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, China.
3. Breast Cancer Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510000, China.
4. Cell genetics laboratory, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, China.
5. Department of Pathology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou510000, P. R. China.
* Sida Peng and Qingqing Yang contributed equally to this work.
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.
Keywords: CTSB, proliferation, tumorigenesis, AML, AKT pathway.