The R-spondin family plays important roles in embryonic development, including in humans. However, information on the relationship between R-spondin2 and hepatocellular carcinoma (HCC) is lacking. This study aimed was to explore the mechanisms of R-spondin2 action in the progression of HCC. By analyzing R-spondin2 expression levels in HCC tissues by IHC and database, we identified that HCC tissues had lower expression levels of R-spondin2, correlated with a poor prognosis. We also established R-spondin2–overexpressing and knockdown cell lines and measured their viabilities and invasion abilities in vitro and their oncogenic capacity in vivo. Human mRNA microarray analysis was performed to screen for mRNAs that were differentially expressed between R-spondin2–overexpressing and control HCC cells. Microarray and Western blot analyses showed significant changes in the MAPK signaling pathway after transfection. Furthermore, in vivo experiments indicated that R-spondin2 knockdown increased the tumorigenicity of HCC cells after subcutaneous implantation in mice. Altogether, our results indicate that the R-spondin2, which might be a novel tumor suppressor gene, were responsible for inhibiting the proliferation and invasion of HCC via the MAPK signaling pathway. Implications: R-spondin2 gene might be a novel tumor suppressor gene providing new clues to clarify the biological behavior of HCC and thus reduce patient mortality and prolong survival.

中文翻译：

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R-spondin2通过MAPK信号通路抑制肝细胞癌的进展

R-spondin 家族在包括人类在内的胚胎发育中发挥着重要作用。然而，缺乏关于 R-spondin2 与肝细胞癌 (HCC) 之间关系的信息。本研究旨在探讨 R-spondin2 在 HCC 进展中的作用机制。通过 IHC 和数据库分析 HCC 组织中 R-spondin2 的表达水平，我们确定 HCC 组织的 R-spondin2 表达水平较低，与预后不良相关。我们还建立了 R-spondin2 过表达和敲低细胞系，并测量了它们的体外活力和侵袭能力以及它们的体内致癌能力。进行人 mRNA 微阵列分析以筛选在 R-spondin2 过表达和对照 HCC 细胞之间差异表达的 mRNA。微阵列和蛋白质印迹分析显示转染后 MAPK 信号通路发生显着变化。此外，体内实验表明，R-spondin2 敲低增加了小鼠皮下植入后 HCC 细胞的致瘤性。总之，我们的结果表明 R-spondin2 可能是一种新的肿瘤抑制基因，它负责通过 MAPK 信号通路抑制 HCC 的增殖和侵袭。启示：R-spondin2基因可能是一种新的抑癌基因，为阐明HCC的生物学行为提供新的线索，从而降低患者死亡率和延长生存期。体内实验表明，R-spondin2 敲低增加了小鼠皮下植入后 HCC 细胞的致瘤性。总之，我们的结果表明 R-spondin2 可能是一种新的肿瘤抑制基因，它负责通过 MAPK 信号通路抑制 HCC 的增殖和侵袭。启示：R-spondin2基因可能是一种新的抑癌基因，为阐明HCC的生物学行为提供新的线索，从而降低患者死亡率和延长生存期。体内实验表明，R-spondin2 敲低增加了小鼠皮下植入后 HCC 细胞的致瘤性。总之，我们的结果表明 R-spondin2 可能是一种新的肿瘤抑制基因，它负责通过 MAPK 信号通路抑制 HCC 的增殖和侵袭。启示：R-spondin2基因可能是一种新的抑癌基因，为阐明HCC的生物学行为提供新的线索，从而降低患者死亡率和延长生存期。