Hongyan Ji1, Li Chen2, Yuqian Xing1, Shanshan Li3, Jianjian Dai4, Ping Zhao5, Yulin Wang1. 1. Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China. 2. Department of Pediatrics, Anhui Provincial Cancer Hospital, Hefei, Anhui, China. 3. Nursing Department, Shandong University Second Affiliated Hospital, Jinan, Shandong, China. 4. Department of Health Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China. 5. Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China. slyyzp123@163.com.
Abstract
BACKGROUND: Stem cell marker CD82 plays a vital role in the oncogenesis and progression of acute myelogenous leukemia (AML), especially in sharing properties of leukemia stem cells (LSCs). The Wnt/β-catenin pathway is required for the development of LSCs in AML. The present study aimed to validate whether CD82 supports the survival of LSCs in pediatric AML via activation of Wnt/β-catenin signaling pathway. METHODS: CD82 expression and its correlation with molecules downstream of Wnt/β-catenin pathway in samples from pediatric AML patients were analyzed. Forced or downregulated expression of CD82 in AML cells was evaluated for the effects of CD82 on cell proliferation, cycle regulation, apoptosis, and adriamycin chemoresistance and to validate the underlying mechanism. RESULT: Aberrant expression of CD82 in pediatric AML patients was found. CD82 messenger RNA expression correlated positively with downstream molecules of Wnt/β-catenin pathway in AML children. Knockdown of CD82 induced apoptosis, suppressed growth, and decreased adriamycin chemoresistance in AML cells. CD82 accelerated β-catenin nuclear location and then stimulated the expression of downstream molecules of Wnt/β-catenin pathway. CONCLUSION: CD82 regulates the proliferation and chemotherapy resistance of AML cells via activation of the Wnt/β-catenin pathway, which suggest that the CD82 may be a potential therapeutic target in AML children.
BACKGROUND: Stem cell marker CD82 plays a vital role in the oncogenesis and progression of acute myelogenous leukemia (AML), especially in sharing properties of leukemia stem cells (LSCs). The Wnt/β-catenin pathway is required for the development of LSCs in AML. The present study aimed to validate whether CD82 supports the survival of LSCs in pediatric AML via activation of Wnt/β-catenin signaling pathway. METHODS:CD82 expression and its correlation with molecules downstream of Wnt/β-catenin pathway in samples from pediatric AMLpatients were analyzed. Forced or downregulated expression of CD82 in AML cells was evaluated for the effects of CD82 on cell proliferation, cycle regulation, apoptosis, and adriamycin chemoresistance and to validate the underlying mechanism. RESULT: Aberrant expression of CD82 in pediatric AMLpatients was found. CD82 messenger RNA expression correlated positively with downstream molecules of Wnt/β-catenin pathway in AMLchildren. Knockdown of CD82 induced apoptosis, suppressed growth, and decreased adriamycin chemoresistance in AML cells. CD82 accelerated β-catenin nuclear location and then stimulated the expression of downstream molecules of Wnt/β-catenin pathway. CONCLUSION:CD82 regulates the proliferation and chemotherapy resistance of AML cells via activation of the Wnt/β-catenin pathway, which suggest that the CD82 may be a potential therapeutic target in AMLchildren.
Authors: Muskan Floren; Sebastian Restrepo Cruz; Christina M Termini; Kristopher D Marjon; Keith A Lidke; Jennifer M Gillette Journal: Oncogene Date: 2020-03-19 Impact factor: 9.867