Zhou Lifang, Zhang Xin, Zhang Chongyang, Wang Yu, Zhang Jiaju, Wang Yunxia, Sui Yongbo
Department of Hepatobiliary Surgery, Cangzhou Hospital of Integrated TCM-WM·Hebei, Cangzhou, China.
Department of Anesthesiology, East Campus of Cangzhou Hospital of Integrated TCM-WM·Hebei, Cangzhou, China.
Cytojournal. 2024 Dec 18;21:66. doi: 10.25259/Cytojournal_91_2024. eCollection 2024.
Hepatocellular carcinoma (HCC) represents a severe and aggressive malignancy with a poor prognosis, characterized by high incidences of illness and death, making it a critical issue for global health. Tyrosyl-tRNA synthetase 1 (YARS1) is known to be upregulated across various cancers and is considerably linked to tumorigenesis. However, the detailed functions and molecular mechanisms of YARS1 in HCC remain unclear. This research explores the expression of YARS1 in HCC and its role in promoting tumor progression through the yes-associated protein 1 (YAP1) pathway.
The potential role and diagnostic significance of YARS1 and YAP1 in HCC were analyzed using relevant datasets. Subsequently, we constructed HCC cell lines with stable knockdown or overexpression of YARS1. , we used Cell Counting Kit-8 and colony formation assays to examine cell proliferation, terminal deoxynucleotidyl transferase dUTP nick end labeling assays to detect apoptosis, and Transwell migration and invasion assays to assess cell metastasis. Western blotting was employed to analyze the molecular mechanisms. Finally, we developed a lung metastasis model for HCC to assess the impact of YARS1 and YAP1 on tumor spread in a living organism, as well as their interrelationship.
The findings revealed a notable increase in YARS1 expression in HCC tumors, associated with a worse prognosis. , YARS1 overexpression significantly increased HCC cell proliferation and metastasis when reducing apoptosis ( < 0.001). In addition, YARS1 overexpression accelerated HCC growth . Further experiments demonstrated that silencing YAP1 effectively reversed the effects of YARS1 on HCC cell invasion ( < 0.01), apoptosis inhibition ( < 0.01), and metastasis ( < 0.001).
In summary, this research reveals that YARS1 enhances the malignant progression of HCC through the activation of the YAP1 signaling pathway. Elevated levels of YARS1 in HCC are strongly linked to poor prognosis, indicating that YARS1 might serve as a new therapeutic target for HCC. Future studies should investigate additional mechanisms of YARS1 in HCC and create targeted therapies to improve outcomes for HCC patients.
肝细胞癌（HCC）是一种严重且侵袭性强的恶性肿瘤，预后较差，其发病率和死亡率都很高，是全球健康的一个关键问题。已知酪氨酰 - tRNA合成酶1（YARS1）在多种癌症中上调，且与肿瘤发生密切相关。然而，YARS1在HCC中的详细功能和分子机制仍不清楚。本研究探讨YARS1在HCC中的表达及其通过Yes相关蛋白1（YAP1）途径促进肿瘤进展的作用。
利用相关数据集分析YARS1和YAP1在HCC中的潜在作用及诊断意义。随后，我们构建了稳定敲低或过表达YARS1的HCC细胞系。我们使用细胞计数试剂盒 - 8和集落形成试验检测细胞增殖，末端脱氧核苷酸转移酶dUTP缺口末端标记试验检测细胞凋亡，Transwell迁移和侵袭试验评估细胞转移。采用蛋白质免疫印迹法分析分子机制。最后，我们建立了HCC肺转移模型，以评估YARS1和YAP1对活体肿瘤扩散的影响及其相互关系。
研究结果显示，HCC肿瘤中YARS1表达显著增加，且与较差的预后相关。此外，YARS1过表达在减少细胞凋亡时显著增加HCC细胞增殖和转移（P < 0.001）。此外，YARS1过表达加速了HCC生长。进一步实验表明，沉默YAP1可有效逆转YARS1对HCC细胞侵袭（P < 0.01）、凋亡抑制（P < 0.01）和转移（P < 0.001）的影响。
总之，本研究表明YARS通过激活YAP1信号通路增强HCC的恶性进展。HCC中YARS1水平升高与不良预后密切相关，表明YARS1可能成为HCC的新治疗靶点。未来研究应探究YARS1在HCC中的其他机制，并开发针对性疗法以改善HCC患者的预后。
