FOXR2 contributes to cell proliferation and malignancy in human hepatocellular carcinoma
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Forkhead box R2 (FOXR2), a member of forkhead box (FOX) family, has been identified as an oncogene in medulloblastoma and breast cancer recently. However, the expression and function of FOXR2 in hepatocellular carcinoma cell (HCC) are still unclear. Here, we report that FOXR2 is frequently upregulated in 25/42 (59.5 %) of HCC specimens compared with neighboring non-cancerous tissues in messenger RNA (mRNA) level and further confirmed by immunohistochemistry analysis in protein level. Cellular function analyses revealed that FOXR2 promoted cell growth and colony formation, whereas knockdown of FOXR2 by RNA inference inhibited cell growth and decreased the growth ability of HCC cells in soft agar. Moreover, we also found FOXR2 overexpression facilitated the development of tumor xenografts in nude mice model. In addition, we validated β-catenin, Skp2, c-Myc, and Gli-1 as the potential downstream effectors of FOXR2 in the regulation of cell proliferation and malignancy by quantitative real-time PCR analysis. Collectively, our data suggest that FOXR2 promotes cell proliferation and malignancy in HCC and could be a novel promising therapeutic target for this disease.
KeywordsHepatocellular carcinoma FOXR2 Cell proliferation Malignancy
This work was supported by grants from the National Natural Science Foundation of China (81302064), Shanghai Natural Science Foundation of China (13ZR1434000), Specialized Research Fund for the Doctoral Program of Higher Education (20130072120060), and Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai (PWZxq2014-04).
Compliance with ethical standards
Sample tissues were obtained from HCC patients by way of surgery and with informed consent in Shanghai East Hospital. The use of human samples and all animal handling and experimental procedures were approved by the Ethics Committee of the Shanghai East Hospital.
Conflicts of interest
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