Huang Qingshan, Li Xiaodong, Huang Zhen, Yu Fengqiang, Wang Xinwen, Wang Shenglin, He Zhizhen, Lin Jianhua
Department of Orthopedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.
Pathol Oncol Res. 2020 Apr;26(2):893-904. doi: 10.1007/s12253-019-00637-w. Epub 2019 Mar 16.
Alpha-actinin-4 (ACTN4) is associated with different types of tumors, but its role in osteosarcoma (OS) is not known. We aimed to investigate the effect of ACTN4 on the growth, migration, invasion and metastasis of OS. We further explored the possible mechanism of how ACTN4 affects the development of OS. First, the expression of ACTN4 in OS tissues and OS cell lines was analyzed by PCR. Second, the role of ACTN4 in the development of OS was explored by the proliferation, scratch, and invasion assays. We further explored the effect of ACTN4 on OS growth in an orthotopic xenograft model of nude mice. In addition, we used hematoxylin and eosin (HE) staining of lung tissues in nude mice to observe the effect of ACTN4 on lung metastasis of OS. Finally, rescue experiments further investigated the role of NF-κB on ACTN4 in the development of OS. ACTN4 was highly expressed in OS tissues and OS cell lines. In vitro experiments demonstrated that reducing ACTN4 expression inhibited the proliferation, migration, and invasion of OS. In contrast, overexpression of ACTN4 promotes these effects. In vivo experiments further validated that ACTN4 promoted the growth of OS. The HE staining of lungs in nude mice revealed that ACTN4 promoted lung metastasis of OS. In addition, we found that ACTN4 enhanced the ability of OS to invade, through the NF-κB pathway. ACTN4 promotes the proliferation, migration, metastasis of OS and enhances its invasion ability through the NF-κB pathway.
α-辅肌动蛋白-4（ACTN4）与不同类型的肿瘤相关，但其在骨肉瘤（OS）中的作用尚不清楚。我们旨在研究ACTN4对骨肉瘤生长、迁移、侵袭和转移的影响。我们进一步探讨了ACTN4影响骨肉瘤发展的可能机制。首先，通过PCR分析ACTN4在骨肉瘤组织和骨肉瘤细胞系中的表达。其次，通过增殖、划痕和侵袭实验探讨ACTN4在骨肉瘤发展中的作用。我们进一步在裸鼠原位异种移植模型中研究ACTN4对骨肉瘤生长的影响。此外，我们对裸鼠肺组织进行苏木精-伊红（HE）染色，以观察ACTN4对骨肉瘤肺转移的影响。最后，挽救实验进一步研究了NF-κB在骨肉瘤发展中对ACTN4的作用。ACTN4在骨肉瘤组织和骨肉瘤细胞系中高表达。体外实验表明，降低ACTN4表达可抑制骨肉瘤的增殖、迁移和侵袭。相反，ACTN4过表达则促进这些作用。体内实验进一步证实ACTN4促进骨肉瘤生长。裸鼠肺组织的HE染色显示ACTN4促进骨肉瘤肺转移。此外，我们发现ACTN4通过NF-κB途径增强骨肉瘤的侵袭能力。ACTN4通过NF-κB途径促进骨肉瘤的增殖、迁移、转移并增强其侵袭能力。
