长链非编码RNA EBLN3P通过增强Annexin A3 mRNA稳定性和招募HuR促进骨肉瘤转移。
LncRNA EBLN3P Facilitates Osteosarcoma Metastasis by Enhancing Annexin A3 mRNA Stability and Recruiting HuR.
发表日期:2023 Aug 19
作者:
Shengtao Wang, Xinxin Zeng, Peng Gui, Shujuan Xu, Zhaoxu Li, Dongxu Chen
来源:
ANNALS OF SURGICAL ONCOLOGY
摘要:
骨肉瘤(OS)是一种常见的骨癌。长链非编码RNA(LncRNA)在OS治疗中显示出潜力。本研究的目的是揭示lncRNA EBLN3P对OS生长和转移的作用及其机制。通过RT-qPCR/Western blot分析确定了EBLN3P/Hu抗原R(HuR)/Annexin A3(ANXA3)的表达。干预EBLN3P/ANXA3/HuR后,通过CCK-8/Transwell实验评估了OS细胞的增殖/迁移/侵袭能力。利用FISH/免疫荧光实验观察EBLN3P/ANXA3/HuR细胞的共定位。通过RNA免疫沉淀/RNA pull-down/RNA稳定性实验评估EBLN3P/ANXA3/HuR之间的相互作用和ANXA3的半衰期。建立裸鼠异种移植模型,并进行EBLN3P处理以评估EBLN3P对OS的功能。EBLN3P/ANXA3在OS细胞中高表达。沉默EBLN3P或ANXA3限制了OS细胞的增殖/迁移/侵袭。从机械上讲,EBLN3P/ANXA3可以与HuR结合,EBLN3P通过招募HuR增强了ANXA3 mRNA的稳定性,从而促进了OS细胞的生长。高表达的HuR或ANXA3对沉默EBLN3P对OS细胞的抑制作用进行了对抗。体内实验显示,EBLN3P通过操纵HuR/ANXA3促进了肿瘤的生长和转移。EBLN3P通过招募HuR增强了OS细胞的增殖/迁移/侵袭能力,从而增加了ANXA3 mRNA的稳定性和蛋白水平,为OS的临床治疗提供了新的潜在治疗靶点。EBLN3P和ANXA3可能在OS的诊断、治疗和预后中发挥潜在作用。本研究为进一步的肿瘤手术临床研究提供了理论参考。© 2023. 作者。
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.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.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.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.© 2023. The Author(s).