PRKD2 Promotes Progression and Chemoresistance of AML via Regulating Notch1 Pathway

• Main Authors: Liu Q, Li W, Zhou Y, Jian J, Han S, Liu C, Zhu X, Ma D, Ji M, Ji C
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-12-01
• Series: OncoTargets and Therapy
• Subjects: prdk2; aml; progression; chemoresistance; notch1
• Online Access: https://www.dovepress.com/prkd2-promotes-progression-and-chemoresistance-of-aml-via-regulating-n-peer-reviewed-article-OTT

Qian Liu,1,2 Wei Li,1 Ying Zhou,1 Jimo Jian,1,3 Shijie Han,4 Chao Liu,5 Wei Li,1 Xunxun Zhu,6 Daoxin Ma,1,7 Min Ji,1 Chunyan Ji1 1Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, People’s Republic of China; 2Department of Pain, Qilu Hospital, Shandong University, Jinan 250012, People’s Republic of China; 3Department of Hematology, Qilu Hospital, Shandong University (Qingdao), Qingdao 266000, People’s Republic of China; 4Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, People’s Republic of China; 5Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250012, People’s Republic of China; 6Department of Hematology, Tengzhou Central People’s Hospital, Tengzhou 277599, People’s Republic of China; 7Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan 250012, People’s Republic of ChinaCorrespondence: Min JiDepartment of Hematology, Qilu Hospital, Shandong University, West Wenhua Road, Jinan 250012, People’s Republic of ChinaEmail [e-mail]: Progression and chemoresistance of acute myeloid leukemia (AML) contribute to most of the treatment failure. Notch pathway has been proven to be involved in many biological processes and diseases, especially AML. In this study, we aimed to explore genes correlated with Notch1 pathway in AML and determine their roles in the regulation of AML progression and chemoresistance.Methods: TCGA database was used to explore Notch1 associated genes. Kaplan–Meier survival analysis was performed to evaluate the prognostic significance of genes. Quantitative RT-PCR (qRT-PCR) and Western blot were performed to examine the expression of genes. The expression of PRKD2 was up-regulated or knocked down in AML cell lines by lentivirus or siRNAs. CCK-8 and flow cytometry were used to analyze the effect of PRKD2 on cell proliferation and chemoresistance.Results: Based on TCGA database, PRKD2 was found to be positively correlated with Notch1 expression, cytogenetic risk status and poorer prognosis in AML. Moreover, the expression level of PRKD2 was higher in AML chemo-resistant cells than in chemo-sensitive cells. Functionally, knockdown of PRKD2-induced apoptosis and increased chemosensitivity of AML cells. PRKD2 overexpression promoted proliferation and chemoresistance of AML cells. Furthermore, we found PRKD2 could regulate Notch1 pathway. Besides, high PRKD2 expression was correlated with higher risk group of AML patients which indicated that PRKD2 was an independent prognostic marker for AML.Conclusion: Taken together, our results showed that PRKD2 could promote the proliferation and chemoresistance of AML cells by regulating Notch1 pathway. The study broadened our insights into the underlying mechanisms in chemoresistance and proliferation of AML, and provided a new prognostic marker and treatment target for AML.Keywords: PRDK2, AML, progression, chemoresistance, Notch1