title: Suppression of CD300A inhibits the growth of diffuse large B-cell lymphoma.
abstract: CD300A is a type I transmembrane receptor protein which has shown inhibitory effects on B-cell receptor-mediated signals. In an analysis of public dataset, we found that CD300A mRNA levels were inversely correlated with the overall survival time of patients with diffuse large B-cell lymphoma (DLBCL). To decipher the role of CD300A in DLBCL, we knocked down the expression levels of CD300A in DLBCL cells and found that decreasing levels of CD300A significantly inhibited cell proliferation of OCI-Ly01, Farage, and SUDHL-4 cells, but not of VAL, OCI-Ly10, or SUDHL-8 cells. Mechanistically, reduced expression of CD300A resulted in a marked attenuation of AKT phosphorylation, a key molecular event in tumorigenesis, in OCI-Ly01, Farage, and SUDHL-4 cells. Pharmacologic inhibition of PI3K displayed a similar inhibitory effect on cell proliferation. Furthermore, using a xenograft animal model, we found that decreasing levels of CD300A in OCI-Ly01 and Farage cells significantly inhibited tumor formation in vivo. Collectively, our results suggested an oncogenic role of CD300A in DLBCL which could serve as a potential biomarker and therapeutic target for this malignant disease.
authors.affiliation: Department of Pathology, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China.
authors.forename: Yulian
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of ENT, Ningbo Second People's Hospital, Ningbo, China.
authors.forename: Xinli
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Ningbo Pathology Service Center, Ningbo, China.
authors.forename: Jianchen
authors.initials: J
authors.lastname: Fang
authors.affiliation: Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
authors.forename: Herbert C
authors.initials: HC
authors.lastname: Morse
authors.affiliation: Department of Pathology, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo, China.
authors.forename: Jeff X
authors.initials: JX
authors.lastname: Zhou
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D049109:Cell Proliferation; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D015703:Antigens, CD; C515070:CD300A protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic
keywords: CD300A; PI3K/AKT; diffuse large B-cell lymphoma; lymphomagenesis