FOXO3 suppresses lymphoma progression through promoting miR‐34b/HSPG2 axis

Author:

Tao Shi1,Huang Qianlei1,Zhou Weilun1,Chen Jing2,Man Yuxuan3,Chen Lang2,Chen Yu1ORCID

Affiliation:

1. Department of Hematology, Hainan Province Clinical Medical Center The First Affiliated Hospital of Hainan Medical University Haikou Hainan Province China

2. School of Preventive Medicine Hainan Medical University Haikou Hainan Province China

3. The First School of Clinical Medicine Hainan Medical University Haikou Hainan Province China

Abstract

AbstractBackgroundDiffuse large B‐cell lymphoma (DLBCL) is the most common type of lymphoma, which caused many patients to lose their precious lives. FOXO3 was a suppressor in various cancers, however, the role and mechanism of FOXO3 in DLBCL remain unclear.MethodsBioinformatics analysis was used to offer information FOXO3 expression and its expression for prognosis of DLBCL patients. The abundance of genes and proteins was evaluated using RT‐qPCR and western blot. Cell proliferation and apoptosis was detected by CCK‐8 and flow cytometry. The interactions among FOXO3, miR‐34b, and HSPG2 were predicted by TransmiR and Starbase and validated using dual luciferase reporter assay, ChIP assay, and RIP assay.ResultsOur findings revealed that FOXO3 expression was abnormally declined in DLBCL cells. FOXO3 upregulation restrained cell proliferation and promoted cell apoptosis of DLBCL cells, while miR‐34b inhibitor eliminated these influences. Similarly, miR‐34b mimic suppressed malignant behaviors of DLBCL cells, which were abolished by HSPG2 overexpression. Mechanically, FOXO3 induced miR‐34b expression through interacting with miR‐34b promoter and HSPG2 was a targeted gene of miR‐34b.ConclusionFOXO3 attenuated the capability of cell proliferation and promoted cell apoptosis rate of DLBCL cells through affecting miR‐34b/HSPG2 axis, therefore inhibiting DLBCL progression.

Publisher

Wiley

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