ABLIM1通过DCC介导的PI3K/AKT信号通路激活促进骨肉瘤的增殖、迁移和侵袭

IF 3.7 2区 生物学 Q2 CELL BIOLOGY
Qi Liao , Siqi Tong , Lan Li , Jianjian Wang , Kai Tong
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引用次数: 0

摘要

肌动蛋白结合LIM蛋白1 (ABLIM1)是LIM结构域蛋白家族的成员,已被确定为一种新的E3泛素连接酶。然而,其确切的生物学功能尚未完全确定。本研究旨在探讨ABLIM1在骨肉瘤细胞生物学行为调控中的作用,并阐明其潜在的分子机制。方法通过综合生物信息学分析和实验验证,表征ABLIM1在骨肉瘤中的失调,并评价其预后意义。为了确定ABLIM1对骨肉瘤细胞增殖、迁移和侵袭的影响,我们进行了全面的体外功能分析,包括CCK-8、EdU掺入、伤口愈合和Transwell侵袭分析。随后对ablim1相关的下游途径进行了Western blotting和代谢谱分析,随后进行了严格的验证实验。最后,我们建立了裸鼠皮下异种移植瘤模型,以评估ABLIM1在体内的功能。结果沉默ABLIM1可显著抑制骨肉瘤细胞的增殖、迁移和侵袭。相反,过表达ABLIM1导致相反的表型。在动物模型中,我们皮下注射沉默的ABLIM1 143B骨肉瘤细胞。结果表明,抑制ABLIM1的表达可抑制骨肉瘤的生长。结论我们的研究结果表明ABLIM1可能是骨肉瘤患者的独立预后因素。ABLIM1通过调控DCC/PI3K/AKT/mTOR轴,促进骨肉瘤细胞的生长、迁移和侵袭。因此,靶向ABLIM1可能成为治疗骨肉瘤的有效靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
ABLIM1 promotes the proliferation, migration and invasion of osteosarcoma through DCC mediated activation of PI3K/AKT signaling pathway

Background

Actin-binding LIM protein 1 (ABLIM1) is a member of the LIM domain protein family and has been identified as a novel E3 ubiquitin ligase. However, its precise biological function remains incompletely characterized. This study aimed to investigate the role of ABLIM1 in modulating the biological behavior of osteosarcoma cells and elucidate the underlying molecular mechanisms.

Methods

Through integrated bioinformatic analyses and experimental validation, we characterized ABLIM1 dysregulation in osteosarcoma and evaluated its prognostic significance. To determine ABLIM1's impact on osteosarcoma cell proliferation, migration, and invasion, we conducted comprehensive in vitro functional assays including CCK-8, EdU incorporation, wound healing, and Transwell invasion analyses. Subsequent investigation of ABLIM1-associated downstream pathways employed Western blotting and metabolic profiling, followed by rigorous validation experiments. Finally, we established a subcutaneous xenograft tumor model in nude mice to assess ABLIM1's in vivo functions.

Results

Silencing ABLIM1 significantly inhibited the proliferation, migration and invasion of osteosarcoma cells. On the contrary, overexpression of ABLIM1 resulted in the converse phenotype. In animal models, we injected silenced ABLIM1 143B osteosarcoma cells subcutaneously. The results showed that inhibiting the expression of ABLIM1 impaired the growth of osteosarcoma.

Conclusion

Our research results indicate that ABLIM1 may be an independent prognostic factor for individuals diagnosed with osteosarcoma. By regulating the DCC/PI3K/AKT/mTOR axis, ABLIM1 promotes the growth, migration and invasion of osteosarcoma cells. Therefore, targeting ABLIM1 may serve as an effective therapeutic target for the treatment of osteosarcoma.
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来源期刊
Cellular signalling
Cellular signalling 生物-细胞生物学
CiteScore
8.40
自引率
0.00%
发文量
250
审稿时长
27 days
期刊介绍: Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.
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