Data from R-spondin2 Suppresses the Progression of Hepatocellular Carcinoma via MAPK Signaling Pathway

Abstract

<div>Abstract<p>The <i>R-spondin</i> 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 <i>R-spondin2</i>–overexpressing and knockdown cell lines and measured their viabilities and invasion abilities <i>in vitro</i> and their oncogenic capacity <i>in vivo</i>. Human mRNA microarray analysis was performed to screen for mRNAs that were differentially expressed between <i>R-spondin2</i>–overexpressing and control HCC cells. Microarray and Western blot analyses showed significant changes in the MAPK signaling pathway after transfection. Furthermore, <i>in vivo</i> experiments indicated that <i>R-spondin2</i> knockdown increased the tumorigenicity of HCC cells after subcutaneous implantation in mice. Altogether, our results indicate that the <i>R-spondin2</i>, which might be a novel tumor suppressor gene, were responsible for inhibiting the proliferation and invasion of HCC via the MAPK signaling pathway.</p>Implications:<p><i>R-spondin2</i> 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.</p></div>