Investigation of the role of HSF1 in HBx-driven progression of hepatocellular carcinoma

Zhan Zongzhu, Wang Chunduo, He Siyi, Li Ranran, Zhang Wuzhiyi, Feng Binbin, Ren Jihua

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Journal of Chongqing Medical University ›› 2025, Vol. 50 ›› Issue (05) : 612-622. DOI: 10.13406/j.cnki.cyxb.003803
Basic research

Investigation of the role of HSF1 in HBx-driven progression of hepatocellular carcinoma

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Abstract

Objective To investigate the role of heat shock transcription factor 1（HSF1） in hepatitis B virus X protein（HBx）-driven migration and invasion of hepatocellular carcinoma（HCC） cells，and to preliminarily explore the mechanism of HSF1 mediating HBx-driven HCC progression. Methods 4D label-free quantitative proteomics and Western blot were used to analyze the effect of HBx on HSF1 expression. HBx was overexpressed in the HCC cell lines Huh7 and MHCC97H，and its impact on the mRNA and protein levels and stability of HSF1 was assessed by RT-PCR and Western blot. The Cancer Genome Atlas database was used to analyze the expression of HSF1 in hepatitis B virus（HBV）-associated HCC tissues and its relationship with tumor stage/grade and patient prognosis，and Western blot was used to measure the expression of HSF1 in HBV-associated HCC tissues. HBx was overexpressed in HCC cells，followed by HSF1 knockdown or cell treatment with the HSF1 inhibitor KRIBB11，and Transwell migration and invasion assay，scratch assay，and F-actin staining experiment were performed to analyze the role of HSF1 in HBx-driven HCC cell migration and invasion. GEO and HCMDB datasets were used to identify the downstream target of HSF1，and the role of downstream target c-Myb in HSF1-mediated HBx-driven HCC progression. Results HBx upregulated HSF1 protein levels without significantly affecting its mRNA expression，through enhancing HSF1 protein stability. HSF1 was highly expressed in HBV-associated HCC tissues，and its elevated expression correlated with tumor stage/grade and poor prognosis. HBx overexpression significantly promoted the migration，invasion，wound-healing capacity，and pseudopodia formation capacity of Huh7 and MHCC97H cells，while HSF1 knockdown or KRIBB11 treatment significantly attenuated the HBx-driven migration and invasion of HCC. HSF1 promoted the expression of the metastasis-associated protein c-Myb，and c-Myb overexpression in HSF1-knockdown HCC cells restored the promotive effect of HBx on HCC cell migration and invasion. Conclusion HBx enhances HSF1 protein stability to promote its expression. Upregulation of c-Myb by HSF1 plays a pivotal role in HBx-driven HCC cell migration and invasion. Targeting HSF1 may help to delay the progression of HBV-associated HCC.

Key words

heat shock transcription factor 1 （HSF1） / HBx / hepatocellular carcinoma （HCC） / migration / invasion

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Zhan Zongzhu , Wang Chunduo , He Siyi , et al . Investigation of the role of HSF1 in HBx-driven progression of hepatocellular carcinoma. Journal of Chongqing Medical University. 2025, 50(05): 612-622 https://doi.org/10.13406/j.cnki.cyxb.003803

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