Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths, but its molecular mechanisms are not yet well characterized. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis, including that of HCC. However, the role of homeobox A11 antisense (HOXA11-AS) in determining HCC stem cell characteristics remains to be explained; hence, this study aimed to investigate the effects of HOXA11-AS on HCC stem cell characteristics. Initially, the expression patterns of HOXA11-AS and HOXA11 in HCC tissues, cells, and stem cells were determined. HCC stem cells, successfully sorted from Hep3B and Huh7 cells, were transfected with short hairpin or overexpression plasmids for HOXA11-AS or HOXA11 overexpression and depletion, with an aim to study the influences of these mediators on the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo. Additionally, the potential relationship and the regulatory mechanisms that link HOXA11-AS, HOXA11, and the Wnt signaling pathway were explored through treatment with Dickkopf-1 (a Wnt signaling pathway inhibitor). HCC stem cells showed high expression of HOXA11-AS and low expression of HOXA11. Both HOXA11-AS silencing and HOXA11 overexpression suppressed the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo, as evidenced by the decreased expression of cancer stem cell surface markers (CD133 and CD44) and stemness-related transcription factors (Nanog, Sox2, and Oct4). Moreover, silencing HOXA11-AS inactivated the Wnt signaling pathway by decreasing the methylation level of the HOXA11 promoter, thereby inhibiting HCC stem cell characteristics. Collectively, this study suggested that HOXA11-AS silencing exerts an antitumor effect, suppressing HCC development via Wnt signaling pathway inactivation by decreasing the methylation level of the HOXA11 promoter.

肝细胞癌（HCC）是癌症相关死亡的主要原因，但其分子机制尚未得到很好的表征。长链非编码 RNA (lncRNA) 在包括 HCC 在内的肿瘤发生中起关键作用。然而，同源框 A11 反义 (HOXA11-AS) 在确定 HCC 干细胞特征中的作用仍有待解释；因此，本研究旨在研究 HOXA11-AS 对 HCC 干细胞特征的影响。最初，确定了 HCC 组织、细胞和干细胞中 HOXA11-AS 和 HOXA11 的表达模式。成功从 Hep3B 和 Huh7 细胞中分选出来的 HCC 干细胞转染 HOXA11-AS 或 HOXA11 过表达和耗竭的短发夹或过表达质粒，旨在研究这些介质对自我更新、增殖、迁移、HCC干细胞在体内的致瘤性和致瘤性。此外，通过用 Dickkopf-1（一种 Wnt 信号通路抑制剂）治疗探索了连接 HOXA11-AS、HOXA11 和 Wnt 信号通路的潜在关系和调节机制。HCC干细胞表现出HOXA11-AS的高表达和HOXA11的低表达。HOXA11-AS 沉默和 HOXA11 过表达均抑制了体内 HCC 干细胞的自我更新、增殖、迁移和致瘤性，癌症干细胞表面标志物（CD133 和 CD44）和干细胞相关转录因子的表达降低就证明了这一点（Nanog、Sox2 和 Oct4）。此外，沉默 HOXA11-AS 通过降低 HOXA11 启动子的甲基化水平使 Wnt 信号通路失活，从而抑制 HCC 干细胞特性。集体，