Tumor-associated macrophages have important roles in hepatocellular carcinoma (HCC) initiation and progression. Long noncoding RNAs (lncRNAs) have also been reported to be involved in HCC. In this study, we explored how lncRNA LINC00662 may influence HCC progression through both tumor cell-dependent and macrophage-dependent mechanisms. LINC00662 was found to be upregulated in HCC, and high LINC00662 levels correlated with poor survival of HCC patients. LINC00662 upregulated WNT3A expression and secretion via competitively binding miR-15a, miR-16, and miR-107. Through inducing WNT3A secretion, LINC00662 activated Wnt/β-catenin signaling in HCC cells in an autocrine manner and further promoted HCC cell proliferation, cell cycle, and tumor cell invasion, while repressing HCC cell apoptosis. In addition, acting through WNT3A secretion, LINC00662 activated Wnt/β-catenin signaling in macrophages in a paracrine manner and further promoted M2 macrophage polarization. Via activating Wnt/β-catenin signaling and M2 macrophages polarization, LINC00662 significantly promoted HCC tumor growth and metastasis in vivo. Hence, targeting LINC00662 may provide novel therapeutic strategy against HCC.

中文翻译：

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长非编码RNA LINC00662通过激活Wnt /β-catenin信号传导促进M2巨噬细胞极化和肝细胞癌进展。

肿瘤相关的巨噬细胞在肝细胞癌（HCC）的发生和发展中具有重要作用。据报道，长非编码RNA（lncRNA）也参与了HCC。在这项研究中，我们探讨了lncRNA LINC00662如何通过肿瘤细胞依赖性和巨噬细胞依赖性机制影响肝癌的进展。发现LINC00662在肝癌中被上调，而高LINC00662水平与肝癌患者的不良生存相关。LINC00662通过竞争性结合miR-15a，miR-16和miR-107上调WNT3A表达和分泌。通过诱导WNT3A分泌，LINC00662以自分泌方式激活了HCC细胞中的Wnt /β-catenin信号传导，并进一步促进了HCC细胞增殖，细胞周期和肿瘤细胞侵袭，同时抑制了HCC细胞凋亡。另外，通过WNT3A分泌作用，LINC00662以旁分泌方式激活巨噬细胞中的Wnt /β-catenin信号传导，并进一步促进M2巨噬细胞极化。通过激活Wnt /β-catenin信号传导和M2巨噬细胞极化，LINC00662显着促进了HCC肿瘤的生长和体内转移。因此，靶向LINC00662可以提供针对HCC的新颖治疗策略。