FOXR2 contributes to cell proliferation and malignancy in human hepatocellular carcinoma
FOXR2 contributes to cell proliferation and malignancy in human hepatocellular carcinoma
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DOI：
10.1007/s13277-016-4923-3
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发表时间：
2016-08-01
期刊：
影响因子：
--
通讯作者：
Li, Yandong
中科院分区：
文献类型：
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作者：
Wang, Xiao;He, Bin;Li, Yandong
叉头盒R2（FOXR 2）是叉头盒（FOX）家族的成员之一，近年来被证实是髓母细胞瘤和乳腺癌的癌基因。然而，FOXR 2在肝细胞癌（HCC）细胞中的表达和功能尚不清楚。在这里，我们报告了FOXR 2在25/42（59.5%）的HCC标本中与邻近的非癌组织相比在信使RNA（mRNA）水平上频繁上调，并通过免疫组织化学分析在蛋白水平上进一步证实。细胞功能分析显示，FOXR 2促进细胞生长和集落形成，而通过RNA干扰的FOXR 2的敲低抑制细胞生长，降低HCC细胞在软琼脂中的生长能力。此外，我们还发现FOXR 2过表达促进了裸鼠移植瘤的发展。此外，我们通过实时定量PCR分析验证了β-连环蛋白、Skp 2、c-Myc和Gli-1作为FOXR 2在细胞增殖和恶性肿瘤调节中的潜在下游效应物。总的来说，我们的数据表明FOXR 2促进HCC中的细胞增殖和恶性化，并且可能是这种疾病的新的有希望的治疗靶点。
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 beta-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.