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Primary research
SETD1A augments sorafenib primary resistance via activating YAP in hepatocellular carcinoma
Yan Gu
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5915-3456
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Sorafenib, the approved first-line chemotherapy drug for HCC, remains the key treatment agent which can effectively improve the survival rate of advanced HCC patients. However, the sorafenib primary resistance limits the application of sorafenib for HCC treatment. The aims of current study are to explore the role and mechanism of SETD1A (Histone Lysine Methyltransferase SET Domain Containing 1A) in sorafenib primary resistance.
Methods: The expression of SETD1A in HCC was analyzed by Gene Expression Profiling Interactive Analysis. The survival of HCC patients was analyzed by KM plotter: Kaplan-Meier Plotter. Western Blot and Real-time qPCR were performed to measure the protein and mRNA levels, respectively. Cell counting kit-8 assay and colony formation assay were performed to determine cell viability and proliferation. Propidium Iodide and Trypan Blue staining assays were performed to investigate cell death.
Results: Here, we showed that the expression of SETD1A was markedly upregulated in both HCC cell lines and tumor tissues compared to normal hepatocytes and corresponding non-tumor liver tissues, respectively. The patients who had higher level of SETD1A underwent lower survival rate of overall and sorafenib treated HCC patients, respectively. In addition, SETD1A expression was positively correlated with the IC50 of sorafenib treated HCC cell lines. Furthermore, we indicated that knockdown of SETD1 augmented proliferation inhibition and cell death induced by sorafenib. SETD1A deficiency impaired YAP phosphorylation and activation. YAP activation contributed to SETD1A mediated sorafenib primary resistance.
Conclusions: Taken together, the current study demonstrated that STED1A enhanced YAP activation to induce sorafenib primary resistance in HCC.
Keywords
SETD1A, hepatocellular carcinoma, sorafenib resistance, YAP
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This is a preprint. It has not completed peer review.
Primary research
SETD1A augments sorafenib primary resistance via activating YAP in hepatocellular carcinoma
Yan Gu
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5915-3456
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 2
Posted 22 May, 2020
No community comments so far
No comments provided
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Sorafenib, the approved first-line chemotherapy drug for HCC, remains the key treatment agent which can effectively improve the survival rate of advanced HCC patients. However, the sorafenib primary resistance limits the application of sorafenib for HCC treatment. The aims of current study are to explore the role and mechanism of SETD1A (Histone Lysine Methyltransferase SET Domain Containing 1A) in sorafenib primary resistance.
Methods: The expression of SETD1A in HCC was analyzed by Gene Expression Profiling Interactive Analysis. The survival of HCC patients was analyzed by KM plotter: Kaplan-Meier Plotter. Western Blot and Real-time qPCR were performed to measure the protein and mRNA levels, respectively. Cell counting kit-8 assay and colony formation assay were performed to determine cell viability and proliferation. Propidium Iodide and Trypan Blue staining assays were performed to investigate cell death.
Results: Here, we showed that the expression of SETD1A was markedly upregulated in both HCC cell lines and tumor tissues compared to normal hepatocytes and corresponding non-tumor liver tissues, respectively. The patients who had higher level of SETD1A underwent lower survival rate of overall and sorafenib treated HCC patients, respectively. In addition, SETD1A expression was positively correlated with the IC50 of sorafenib treated HCC cell lines. Furthermore, we indicated that knockdown of SETD1 augmented proliferation inhibition and cell death induced by sorafenib. SETD1A deficiency impaired YAP phosphorylation and activation. YAP activation contributed to SETD1A mediated sorafenib primary resistance.
Conclusions: Taken together, the current study demonstrated that STED1A enhanced YAP activation to induce sorafenib primary resistance in HCC.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5