Tumor Biology

, Volume 37, Issue 8, pp 10459–10467 | Cite as

FOXR2 contributes to cell proliferation and malignancy in human hepatocellular carcinoma

  • Xiao Wang
  • Bin He
  • Yong Gao
  • Yandong LiEmail author
Original Article


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.


Hepatocellular 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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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  1. 1.Department of Oncology and Hematology, Shanghai East HospitalTongji University School of MedicineShanghaiChina
  2. 2.Department of Oncology, East HospitalDalian Medical UniversityShanghaiChina
  3. 3.Research Center for Translational Medicine, Shanghai East HospitalTongji University School of MedicineShanghaiChina

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