Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most frequent and commonly diagnosed subtype of NHL, which is characterized by high heterogeneity and malignancy, and most DLBCL patients are at advanced stages. The serine/threonine kinase NEK2 (NIMA-related kinase 2), a member of NIMA-related kinase (NEK) family that regulates cell cycle, is upregulated in a variety of malignancies, including diffuse large B-cell lymphoma. However, the role and underlying mechanisms of NEK2 in DLBCL have seldom been discussed. In this study, we identified that NEK2 is upregulated in DLBCL compared to normal lymphoid tissues, and overexpression of NEK2 predicted a worse prognosis of DLBCL patients. Gene set enrichment analysis indicates that NEK2 might participate in regulating glycolysis. Knockdown of NEK2 inhibited growth and glycolysis of DLBCL cells. The interaction between NEK2 and PKM2 was discovered by tandem affinity purification and then was confirmed by immunofluorescence staining, coimmunoprecipitation, and immunoprecipitation. NEK2 bounds to PKM2 and regulates PKM2 abundance via phosphorylation, which increases PKM2 stability. The xenograft tumor model checks the influence of NEK2 on tumor growth in vivo. Thus, NEK2 could be the novel biomarker and target of DLBCL, which remarkably ameliorates the diagnosis and treatment of DLBCL.
Highlights
Non-Hodgkin lymphoma (NHL) accounts for 4% of the total number of new cancer cases recorded in 2020, ranked seventh among all cancer types [1]
On the basis of bioinformatic analyses, we demonstrated that NEK2 was upregulated in Diffuse large B-cell lymphoma (DLBCL) compared to normal lymphoid tissue, and overexpression of NEK2 predicted a worse prognosis of DLBCL patients
NEK2 was highly expressed in DLBCL compared with normal lymphoid tissues (Figures 1A–C)
Summary
Non-Hodgkin lymphoma (NHL) accounts for 4% of the total number of new cancer cases recorded in 2020, ranked seventh among all cancer types [1]. Diffuse large B-cell lymphoma (DLBCL) is the most frequent and commonly diagnosed subtype of NHL, which is characterized by high heterogeneity and malignancy, and most DLBCL patients are at advanced stages [2]. Investigating the regulatory mechanisms promoting tumor cell growth and exploring novel biomarkers of DLBCL could remarkably ameliorate the diagnosis and treatment of DLBCL. Due to the signaling and biological significance of kinases, there have been extensive efforts to investigate the mechanism of kinase in tumors, which contributing to developing selective kinase inhibitors with novel treatment opportunities [5]. NEK2 was found to be upregulated in DLBCL compared to Follicular lymphoma (FL), the latter exhibit relatively low malignancy [7]. Our further differential expression analysis showed that NEK2 is upregulated in DLBCL compared to normal lymphoid tissues. As disease-specific differential expression genes reveal potential disease-related molecular mechanisms, NEK2 might play an important role in DLBCL
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
