乙型肝炎病毒（HBV）编码的X抗原，HBx，通过复杂的机制促进肝细胞癌（HCC）的发展。我们的研究结果为EZ2H介导的let-7c的表观遗传抑制提供了新的见解，这促进了HBx诱导的HCC迁移。因此，let-7c和HMGA2代表了HBV相关HCC诊断标志物和潜在治疗靶点。我们研究了HBV相关HCC细胞中重要代表性miRNA let-7c的表观调控，以验证HBx的作用。在24例HBV相关HCC患者的肿瘤和相邻非肿瘤肝组织中，通过定量PCR（qPCR），我们发现EZH2在大多数HCC组织中明显高表达（87.5%）。我们对这些患者的6对HBV相关HCC肿瘤组织和相邻非肿瘤肝组织进行了miRNA微阵列分析，并发现let-7c、miR-199a-3p和miR-99a在肿瘤组织中下调。实时PCR分析证实，相对于母细胞，稳定过表达HBx的HepG2X和Hep3BX细胞中，let-7c和miR-99a明显下调。HBx增强了HCC细胞中EZH2的表达，抑制了let-7c的表达，并诱导了HMGA2的表达。HMGA2的沉默显著降低了HBx诱导的HCC细胞转移能力。HBx通过调节let-7c的表达失调可能是一个潜在的新通路，该通路通过失调细胞转移并暗示HMGA2可能被用作HCC的新的预后标志物和/或有效治疗靶点。© 2023. BioMed Central Ltd., Springer Nature的一部分。

Hepatitis B virus (HBV)-encoded X antigen, HBx, assists in the development of hepatocellular carcinoma (HCC) through complex mechanisms. Our results provide new insights into the EZH2 epigenetic repression of let-7c that promotes HCC migration induced by HBx. Thus, let-7c and HMGA2 represent key diagnostic markers and potential therapeutic targets for the treatment of HBV-related HCC.We investigated the epigenetic regulation of let-7c, an important representative miRNA in liver tumor metastasis, in human HCC cells to verify the effect of HBx. Based on quantitative PCR (qPCR) of mRNA isolated from tumor and adjacent non-tumor liver tissues of 24 patients with HBV-related HCC, EZH2 expression was significantly overexpressed in most HCC tissues (87.5%). We executed a miRNA microarray analysis in paired HBV-related HCC tumor and adjacent non-tumorous liver tissue from six of these patients and identified let-7c, miR-199a-3p, and miR-99a as being downregulated in the tumor tissue. Real-time PCR analysis verified significant downregulation of let-7c and miR-99a in both HepG2X and Hep3BX cells, which stably overexpress HBx, relative to parental cells. HBX enhanced EZH2 expression and attenuated let-7c expression to induce HMGA2 expression in the HCC cells. Knockdown of HMGA2 significantly downregulated the metastatic potential of HCC cells induced by HBx.The deregulation of let-7c expression by HBx may indicate a potential novel pathway through deregulating cell metastasis and imply that HMGA2 might be used as a new prognostic marker and/or as an effective therapeutic target for HCC.© 2023. BioMed Central Ltd., part of Springer Nature.