LncRNA EBLN3P Facilitates Osteosarcoma Metastasis by Enhancing Annexin A3 MRNA Stability and Recruiting HuR

Overview

Journal Ann Surg Oncol

Publisher Springer

Specialty Oncology

Date 2023 Aug 19

PMID 37598115

Authors

Shengtao Wang

Xinxin Zeng

Peng Gui

Shujuan Xu

Zhaoxu Li

Dongxu Chen

Affiliations

Soon will be listed here.

Abstract

Background: Osteosarcoma (OS) represents a common type of bone cancer. Long non-coding RNAs (LncRNAs) have shown their potential in therapeutic modalities for OS. This study's purpose was to reveal the action of lncRNA EBLN3P on OS growth and metastasis and its mechanism.

Methods: Expressions of EBLN3P/Hu antigen R (HuR)/Annexin A3 (ANXA3) were determined by RT-qPCR/Western blot. Proliferation/migration/invasion of OS cells were assessed via CCK-8/Transwell assays after interfering EBLN3P/ANXA3/HuR. The co-localization of EBLN3P/ANXA3/HuR cells was observed by FISH/immunofluorescence assays. Interplays among EBLN3P/ANXA3/HuR and the half-life period of ANXA3 were assessed by RNA immunoprecipitation/RNA pull-down/RNA stability experiment. The nude mouse xenograft model was established, followed by EBLN3P treatment to assess the function of EBLN3P on OS.

Results: EBLN3P/ANXA3 was highly expressed in OS cells. Silencing EBLN3P or ANXA3 limited the proliferation/migration/invasion of OS cells. Mechanically, EBLN3P/ANXA3 can bind to HuR, and EBLN3P enhanced ANXA3 mRNA stability by recruiting HuR, thus facilitating OS cell growth. Upregulated HuR or ANXA3 counteracted the suppressive action of silencing EBLN3P on OS cells. In vivo experiments revealed facilitated tumor growth and metastasis in vivo fomented by EBLN3P through manipulation of HuR/ANXA3.

Conclusions: EBLN3P enhanced proliferative/migrative/invasive potentials of OS cells via increasing ANXA3 mRNA stability and protein level by recruiting HuR, which provided new potential therapeutic targets for OS clinical treatment. EBLN3P and ANXA3 might have potential roles in OS diagnosis, treatment, and prognosis. This study provided a theoretical reference for further clinical research in tumor surgery.

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