IRF2 Destabilizes Oncogenic KPNA2 to Modulate the Development of Osteosarcoma

Overview

Journal J Oncol

Specialty Oncology

Date 2022 Oct 6

PMID 36199790

Authors

Shuchi Xia

Yiqun Ma

Affiliations

Soon will be listed here.

Abstract

Osteosarcomas (OS) are the most common primary malignant bone tumor. Emerging evidence revealed that karyopherin alpha 2 (KPNA2) was strongly associated with the tumorigenesis and development of numerous human cancers. The aim of the present study was to investigate the expression pattern, biological functions, and underlying mechanism of KPNA2 in OS. Bioinformatics TFBIND online was applied to forecast transcription factor (TF) binding sites in the promoter region of KPNA2. The expression profile of KPNA2 in OS tissues were firstly assessed. CCK8, colony formation, wound healing, and Transwell assays were used to assess cell viability, proliferation, and migration in vitro, and in vivo experiments were performed to explore the effects of KPNA2 and interferon regulatory factor-2 (IRF2) on tumor growth. Furthermore, the correlation between IRF2 and KPNA2 was investigated using chromatin immunoprecipitation (ChIP), RT-qPCR, western blot, and dual-luciferase assays. KPNA2 was obviously upregulated, while IRF2 decreased significantly in OS tissues and cell lines, as well as negatively correlated with each other. KPNA2 removal remarkably suppressed OS cell growth, migration, invasion in vitro, and tumor growth in vivo, while IRF2 knockdown exerts an opposing effect. IRF2 binds to the KPNA2 promoter to modulate the malignant phenotypes of OS cells by regulating epithelial-to-mesenchymal transition (EMT). The present study demonstrated that KPNA2 performed the oncogenic function, possibly regulating tumor development through EMT. Importantly, it was confirmed that IRF2 serves as a potential upstream TF of KPNA2 involved in the regulation of EMT progress in OS.

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