Slow skeletal muscle troponin T acts as a potential prognostic biomarker and therapeutic target for hepatocellular carcinoma

[Display omitted] •TNNT1 was upregulated in HCC tissues compared with the adjacent non-tumoral liver.•Serum TNNT1 was upregulated in HCC patients compared with healthy donors.•TNNT1 may serve as a potential prognostic and diagnostic biomarker for HCC.•Anti-TNNT1 inhibited oncogenic behaviors and EMT...

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Veröffentlicht in:Gene 2023-05, Vol.865, p.147331-147331, Article 147331
Hauptverfasser: Huang, Shih-Chung, Huang, Chao-Cheng, Ko, Chou-Yuan, Huang, Cheng-Yi, Liu, Ching-Han, Lee, Yung-Kuo, Chen, Tung-Yuan, Hsueh, Chao-Wen, Tzou, Shiow-Jyu, Tai, Ming-Hong, Hu, Tsung-Hui, Tsai, Ming-Chao, Lee, Wen-Chin, Ho, Yu-Cheng, Wu, Cheng-Chun, Chang, Yi-Chen, Chang, Jung-Jui, Liu, Kai-Hsi, Li, Chiao-Ching, Wen, Zhi-Hong, Chang, Chen-Lin, Chu, Tian-Huei
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Sprache:eng
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Zusammenfassung:[Display omitted] •TNNT1 was upregulated in HCC tissues compared with the adjacent non-tumoral liver.•Serum TNNT1 was upregulated in HCC patients compared with healthy donors.•TNNT1 may serve as a potential prognostic and diagnostic biomarker for HCC.•Anti-TNNT1 inhibited oncogenic behaviors and EMT in hepatoma cells.•TNNT1 may act as a novel therapeutic target for HCC control. Slow skeletal muscle troponin T (TNNT1) as a poor prognostic indicator is upregulated in colon and breast cancers. However, the role of TNNT1 in the disease prognosis and biological functions of hepatocellular carcinoma (HCC) is still unclear. The Cancer Genome Atlas (TCGA), real-time quantitative RT-PCR (qRT-PCR), immunoblot, and immunohistochemical analyses were applied to evaluate the TNNT1 expression of human HCC. The impact of TNNT1 levels on disease progression and survival outcome was studied using TCGA analysis. Moreover, the bioinformatics analysis and HCC cell culture were used to investigate the biological functions of TNNT1. Besides, the immunoblot analysis and enzyme-linked immunosorbent assay (ELISA) were used to detect the extracellular TNNT1 of HCC cells and circulating TNNT1 of HCC patients, respectively. The effect of TNNT1 neutralization on oncogenic behaviors and signaling was further validated in the cultured hepatoma cells. In this study, tumoral and blood TNNT1 was upregulated in HCC patients based on the analyses using bioinformatics, fresh tissues, paraffin sections, and serum. From the multiple bioinformatics tools, the TNNT1 overexpression was associated with advanced stage, high grade, metastasis, vascular invasion, recurrence, and poor survival outcome in HCC patients. By the cell culture and TCGA analyses, TNNT1 expression and release were positively correlated with epithelial-mesenchymal transition (EMT) processes in HCC tissues and cells. Moreover, TNNT1 neutralization suppressed oncogenic behaviors and EMT in hepatoma cells. In conclusion, TNNT1 may serve as a non-invasive biomarker and drug target for HCC management. This research finding may provide a new insight for HCC diagnosis and treatment.
ISSN:0378-1119
1879-0038
DOI:10.1016/j.gene.2023.147331