Abstract
Hepatocellular carcinoma (HCC) is one of the deadliest cancer types worldwide. The centromere proteins (CENPs) are critical for the mitosis-related protein complex and are involved in kinetochore assembly and spindle checkpoint signaling during mitosis. However, the clinical significance of CENPs in the recurrence and progression of HCC remains poorly understood. Here, we examined the expression of all CENPs and their association with recurrence and survival of HCC patients using the global gene expression profile dataset established in our laboratory. The effect of silencing CENPF on cell viability, migration, and epithelial-mesenchymal transition (EMT) were detected using CCK-8, transwell, and western blot, respectively. RT-qPCR and western blot were performed to confirm the silencing of CENPF and the relationship between STAT5A and CENPF, while tumorigenesis was tested using the HCC Huh7 xenograft mouse model. Most of the CENPs is overexpressed in HCC, and overexpression of CENPF was significantly associated with the poor survival of HCC patients. CENPF promoted HCC cell lines migration and EMT progression. Knockdown CENPF inhibited cell growth activity against human HCC cells in vitro and xenograft tumors in vivo. Bioinformatics analysis revealed that CENPF genes are enriched in the cell cycle. Silencing CENPF arrested cell cycle at the G2/M phase and inhibited Cyclin B1 and Cyclin E1 expressions. Meanwhile, silencing CENPF prohibited phosphorylation of ERK and the expression of NEK2. Additionally, we found that STAT5A down-regulated CENPF expression and inhibited cancer cell growth viability. In conclusion, our data suggested that CENPF could be potentially developed into a theranostic biomarker to tackle HCC progression.
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Acknowledgements
This work was supported by grants from the National Medical Research Council (NMRC) of Singapore, The Recruitment Program of Overseas High-Level Young Talents, National Natural Science Foundation of China (82072739), “Innovative and Entrepreneurial Team” (No. (2018)2015), Science and Technology Grant (BE2019758) and the Six Talent Peaks Project (TD-SWYY-007) of Jiangsu Province and High-Level Talents Program of Nanjing Medical University, and Chinese Foundation for Hepatitis Prevention and Control-Tian Qing Liver Disease Research Fund (TQGB20190164, TQGB20200139). The China Scholarship Council [201908320572 to H.C.] and Nanjing Medical University Scholarship [C124 to H.C.].
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H.C., K.H., and H.X. conceived the idea and designed the experiments. H.C. and H.X. carried out the experiments. F.W., F.X., and G.Z. contributed to the clinical samples and analysis. G.W., M.D., and A.D. help the experimental and analysis. H.C. wrote the paper with input from all authors. All authors read and approved the final paper.
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Chen, H., Wu, F., Xu, H. et al. Centromere protein F promotes progression of hepatocellular carcinoma through ERK and cell cycle-associated pathways. Cancer Gene Ther 29, 1033–1042 (2022). https://doi.org/10.1038/s41417-021-00404-7
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DOI: https://doi.org/10.1038/s41417-021-00404-7
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