FOXR2 contributes to cell proliferation and malignancy in human hepatocellular carcinoma

• Published in: Tumor biology Vol. 37; no. 8; pp. 10459 - 10467
• Main Authors: Wang, Xiao, He, Bin, Gao, Yong, Li, Yandong
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.08.2016; Springer Nature B.V
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Division; Cell growth; Cell Line, Tumor; Cellular biology; Forkhead Transcription Factors - biosynthesis; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - physiology; Gene Expression Regulation, Neoplastic; Heterografts; Humans; Liver - metabolism; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Neoplasm Proteins - physiology; Original Article; Ribonucleic acid; RNA; RNA, Messenger - biosynthesis; RNA, Neoplasm - biosynthesis; Tumor Stem Cell Assay; Up-Regulation; FOXR2; Cell proliferation; Hepatocellular carcinoma; Malignancy
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-016-4923-3

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.