Deciphering the synergistic role of tyrosyl-tRNA synthetase 1 and yes-associated protein 1: Catalysts of malignant progression in hepatocellular carcinoma.

OBJECTIVE

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.

MATERIAL AND METHODS

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.

RESULTS

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).

CONCLUSION

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.