Hepatocellular carcinoma (HCC) is an extraordinarily heterogeneous tumor, which holds high recurrence and metastasis rates. Liver cancer stem cells (LCSCs) have been considered to be important influencing factors of these pathological properties, but the underlying mechanisms are poorly understood in HCC. Considerable evidences have shown that autophagy has an important role in cancer stemness. However, it is still unknown whether a long noncoding RNA (lncRNA) TINCR is involved in autophagy and self-renewal maintenance of HCC. In this study, TINCR was found to be highly expressed in HCC tissues and LCSCs. In vitro and in vivo assays for the first time showed that TINCR was required for LCSC self-renewal and tumorigenesis. Moreover, gene ontology analysis revealed the involvement of autophagy in the maintenance of TINCR-regulated stemness. Mechanically, TINCR was associated with polypyrimidine tract binding protein 1 (PTBP1) protein, which further promoted the transcription activity of autophagy related gene ATG5. In conclusion, we demonstrated that TINCR regulated LCSC self-renewal by autophagy activation through PTBP1/ATG5 regulatory pathway, offering a potential new target for HCC therapy.

肝细胞癌（HCC）是一种异质性极强的肿瘤，具有很高的复发率和转移率。肝癌干细胞 (LCSCs) 被认为是这些病理特性的重要影响因素，但对 HCC 的潜在机制知之甚少。大量证据表明，自噬在癌症干细胞中具有重要作用。然而，长链非编码RNA（lncRNA）TINCR是否参与HCC的自噬和自我更新维持尚不清楚。在这项研究中，发现 TINCR 在 HCC 组织和 LCSC 中高表达。体外和体内试验首次表明 TINCR 是 LCSC 自我更新和肿瘤发生所必需的。此外，基因本体分析揭示了自噬参与维持 TINCR 调节的干性。在机械上，TINCR 与聚嘧啶束结合蛋白 1 (PTBP1) 蛋白相关，进一步促进自噬相关基因 ATG5 的转录活性。总之，我们证明了 TINCR 通过 PTBP1/ATG5 调节通路激活自噬来调节 LCSC 自我更新，为 HCC 治疗提供了一个潜在的新靶点。