Northern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.
Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, 225001, China.
Dig Dis Sci. 2024 Oct;69(10):3786-3798. doi: 10.1007/s10620-024-08649-6. Epub 2024 Sep 25.
Actin-like protein 8 (ACTL8) significantly correlates with tumor growth and prognosis across various cancer types. Nevertheless, the potential relationship between ACTL8 and gastric cancer (GC) remains uncertain.
This study aimed to elucidate the role of ACTL8 in human GC cells and to explore its mechanism.
Bioinformatics analysis tools, such as GEPIA2, Kaplan-Meier, and STRING, were utilized for a comprehensive investigation of the characteristics and functional roles of ACTL8 in GC, including differential expression, prognostic value, and related signaling pathways. Subsequently, gene expression analyses, cell function assays, and signaling pathway experiments were conducted to verify key findings.
Bioinformatics analysis showed that ACTL8 was significantly elevated in GC and closely associated with poor prognosis. Gene expression experiments confirmed the bioinformatics results. Furthermore, ACTL8 knockdown markedly reduced GC cell proliferation and inhibited migration and invasion. Mechanistically, a significant increase in the phosphorylation levels of signaling proteins was observed in GC cells following ACTL8 overexpression, and PI3K/Akt/mTOR pathway inhibitors could reverse this effect.
ACTL8 expression is significantly upregulated in GC cells and is closely correlated with poor patient prognosis. Further mechanistic studies revealed that ACTL8 may promote GC cell migration and proliferation through activation of the PI3K/Akt/mTOR signaling pathway. Consequently, ACTL8 emerges as a promising therapeutic target for GC.
肌动蛋白样蛋白 8（ACTL8）与多种癌症类型的肿瘤生长和预后显著相关。然而，ACTL8 与胃癌（GC）之间的潜在关系尚不确定。
本研究旨在阐明 ACTL8 在人 GC 细胞中的作用及其机制。
利用 GEPIA2、Kaplan-Meier 和 STRING 等生物信息学分析工具，全面研究 ACTL8 在 GC 中的特征和功能作用，包括差异表达、预后价值和相关信号通路。随后，进行基因表达分析、细胞功能测定和信号通路实验，以验证关键发现。
生物信息学分析表明，ACTL8 在 GC 中显著上调，与不良预后密切相关。基因表达实验证实了生物信息学的结果。此外，ACTL8 敲低显著降低 GC 细胞的增殖，并抑制迁移和侵袭。机制上，ACTL8 过表达后观察到 GC 细胞中信号蛋白的磷酸化水平显著增加，而 PI3K/Akt/mTOR 通路抑制剂可以逆转这种效应。
ACTL8 在 GC 细胞中表达显著上调，与患者预后不良密切相关。进一步的机制研究表明，ACTL8 可能通过激活 PI3K/Akt/mTOR 信号通路促进 GC 细胞的迁移和增殖。因此，ACTL8 成为 GC 的一个有前途的治疗靶点。
