Abstract
Cancer stem-like cells (CSCs) play a key role in maintaining the aggressiveness of hepatocellular carcinoma (HCC), but the cell-biological regulation of CSCs is unclear. In the study, we report that thyroid hormone (TH) promotes cell self-renewal in HCC cells. TH also increases the percentage of CD90 + HCC cells and promotes drug resistance of HCC cells. By analyzing primary human HCC samples, we found that TRα transcript level is significantly elevated in primary liver cancer and portal vein metastatic tumor, compared to that of adjacent normal liver tissue. Knocking down TRα not only inhibits HCC self-renewal in vitro but also suppresses HCC tumor growth in vivo. Interestingly, treatment of TH leads to activation of NF-κB, which is required for the function of TH on inducing HCC cell self-renewal. We also found TRα and p65 cooperatively drive the expression of BMI1 by co-binding to the promoter region of BMI1 gene. In summary, our study uncovers a novel function of TH signaling in regulating the CSCs of HCC, and these findings might be useful for developing novel therapies by targeting TH function in HCC cells.
Highlights
In this study, we found that TH significantly increased cell self-renewal in Hepatocellular carcinoma (HCC) cells
We have reported that CSQT-2 manifests many features of advanced HCC, including potent self-renewal capacity, multi-drug resistance, and vasculature metastatic potential[12]
We set out to investigate the function of TH in regulating the cancer stem-like cells (CSCs) of hepatocellular carcinoma, and revealed that TH can induce HCC cell self-renewal, increase the percentage of CD90 + HCC cells, and promotes drug resistance of HCC cells
Summary
We found that TH significantly increased cell self-renewal in HCC cells. TH increases the number of CD90 + HCC cells and promoted drug resistance in HCC cells. Loss-of-function experiments revealed that decreasing TRα expression significantly suppressed both in vitro cell self-renewal and in vivo tumor growth of HCC cells. By analyzing primary human HCC samples, we found that TRα transcript level was significantly elevated in primary liver cancer and portal vein metastatic tumor, compared to that in adjacent normal liver tissue. We found that the function of TH signaling co-operatives with NF-κ B in HCC cells. TRα interacts with NF-κ B subunit p65 and co-occupies the promoter region of oncogene BMI1 in TH-treated HCC cells. Our study demonstrated a critical role of TH signaling in self-renewal of liver CSCs
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
