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BARX1 通过调节 HSPA6 的表达促进骨肉瘤细胞的增殖和侵袭。

BARX1 promotes osteosarcoma cell proliferation and invasion by regulating HSPA6 expression.

机构信息

Department of Orthopaedic Oncology, The Second Affiliated Hospital of Naval Medical University, No. 415 Fengyang Road, Huangpu District, Shanghai, 200003, China.

Department of Laboratory Medicine, Changzheng Hospital, Naval Medical University, No. 415 Fengyang Road, Huangpu District, Shanghai, 200003, China.

出版信息

J Orthop Surg Res. 2023 Mar 16;18(1):211. doi: 10.1186/s13018-023-03690-z.

Abstract

Osteosarcoma (OS) is a bone tumour affecting adolescents. Dysregulation of Barx homeobox 1 (BARX1) expression is involved in various cancers, but its function and mechanism in the process of OS are undefined. This study revealed that BARX1 expression is higher in OS tissue than in adjacent normal tissue. Downregulation of BARX1 in OS cells significantly suppressed their proliferation and migration, whereas enforced expression of exogenous BARX1 exerted the opposite effects on OS cells. Subsequently, heat shock 70-kDa protein 6 (HSPA6) expression was clearly increased after BARX1 overexpression in OS cells, as confirmed by RNA sequencing. The dual-luciferase reporter assay confirmed that HSPA6 expression is directly regulated by BARX1. The in vitro assay indicated that silencing HSPA6 expression attenuated OS proliferation and migration induced by BARX1. A dual immunofluorescence labelling assay provided further evidence that BARX1 was overexpressed and associated with HSPA6 overexpression in OS tumour tissue. In conclusion, BARX1 promotes OS cell proliferation and migration by inducing the expression of HSPA6, which plays an oncogenic role in OS. BARX1 and HSPA6 can potentially act as novel therapeutic targets for OS.

摘要

成骨肉瘤(OS)是一种影响青少年的骨肿瘤。Barx 同源盒 1(BARX1)表达失调与多种癌症有关,但它在 OS 过程中的功能和机制尚未确定。本研究表明,BARX1 在 OS 组织中的表达高于相邻正常组织。OS 细胞中 BARX1 的下调显著抑制了其增殖和迁移,而外源性 BARX1 的过表达对 OS 细胞则产生相反的影响。随后,通过 RNA 测序证实,BARX1 过表达后 OS 细胞中热休克 70kDa 蛋白 6(HSPA6)的表达明显增加。双荧光素酶报告基因检测证实 HSPA6 的表达受 BARX1 的直接调控。体外实验表明,沉默 HSPA6 的表达可减弱 BARX1 诱导的 OS 增殖和迁移。双重免疫荧光标记实验进一步证明 BARX1 在 OS 肿瘤组织中过表达,并与 HSPA6 的过表达相关。总之,BARX1 通过诱导 HSPA6 的表达促进 OS 细胞的增殖和迁移,在 OS 中发挥致癌作用。BARX1 和 HSPA6 可能成为 OS 的新型治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7f9/10018937/c9deb308a059/13018_2023_3690_Fig1_HTML.jpg

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