Transarterial chemoembolization (TACE) has been considered the standard treatment for intermediate-stage hepatocellular carcinoma according to BCLC algorithm. However, it has been unclear about the TACE-related predictive bio-markers and underlying molecular mechanisms. This investigation revealed that HCCs with higher HIF-1α suffered from unfavorable OS after TACE. mRNA expression microarray revealed that HIF-1α was potential target of p-STAT3 which was verified by ChIP and immunoblotting assay. Activation of IL-6/STAT3/HIF-1α signaling was found to promote EMT and chemoresistance to Doxorubicin and by regulating SNAI1. Hypoxia did not enhance HIF-1α expression and influence cell growth and chemoresistence to Doxorubicin in HCC cells when STAT3 expression was abolished. Taken together, HIF-1α overexpression in HCC tissues predicted the unfavorable outcome of HCCs after TACE and IL-6/STAT3 pathway resulted in EMT induced-metastases and chemoresistance of HCC after TACE through HIF-1α/SNAI1 axis.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959052 | PMC |
| http://dx.doi.org/10.7150/jca.35631 | DOI Listing |
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