title: FOXR2 contributes to cell proliferation and malignancy in human hepatocellular carcinoma.
abstract: 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.
authors: Department of Oncology and Hematology, Shanghai East Hospital, Tongji University School of Medicine, 150 Ji-Mo Road, Shanghai, 200120, China.|Department of Oncology, East Hospital, Dalian Medical University, Shanghai, 200120, China.
authors: Xiao
authors: X
authors: Wang
authors: Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
authors: Bin
authors: B
authors: He
authors: Department of Oncology and Hematology, Shanghai East Hospital, Tongji University School of Medicine, 150 Ji-Mo Road, Shanghai, 200120, China.
authors: Yong
authors: Y
authors: Gao
authors: Department of Oncology and Hematology, Shanghai East Hospital, Tongji University School of Medicine, 150 Ji-Mo Road, Shanghai, 200120, China. yandongli2009@gmail.com.
authors: Yandong
authors: Y
authors: Li
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D045744:Cell Line, Tumor; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation
chemical_list: C499816:FOXR2 protein, human; D051858:Forkhead Transcription Factors; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm
keywords: Cell proliferation; FOXR2; Hepatocellular carcinoma; Malignancy