Helicase-like transcription factor (HLTF) has been found to be involved in the progression of several tumors, but the role of HLTF in hepatocellular carcinoma (HCC) progression has not been studied. Here, our study explored the underlying mechanism of HLTF in HCC progression for the first time. Database analysis and clinical sample examination indicated that HLTF was upregulated in HCC tissues and was related to poor clinicopathological features in patients. Upregulation of HLTF accelerated the growth and metastasis of HCC cells both in vitro and in vivo. Bioinformatics analysis and subsequent experiments revealed that ERK/MAPK signaling pathway activation was vital to HLTF-mediated proliferation and metastasis in HCC cells. Moreover, HLTF was demonstrated to interact with SRSF1 and contribute to its protein stability to activate the ERK/MAPK signaling pathway and enhance HCC growth and metastasis. In addition, miR-511-5p was expressed at a low level in HCC tissues, was negatively correlated HLTF, and regulated HLTF expression. Our study shows that HLTF plays an oncogenic role in HCC progression and provides a novel biomarker and therapeutic target for the diagnosis and treatment of HCC.

已发现解旋酶样转录因子 (HLTF) 参与多种肿瘤的进展，但尚未研究 HLTF 在肝细胞癌 (HCC) 进展中的作用。在这里，我们的研究首次探讨了 HLTF 在 HCC 进展中的潜在机制。数据库分析和临床样本检查表明，HLTF 在 HCC 组织中上调，并且与患者的临床病理特征较差有关。HLTF 的上调加速了 HCC 细胞在体外和体内的生长和转移。生物信息学分析和随后的实验表明，ERK/MAPK 信号通路激活对于 HLTF 介导的 HCC 细胞增殖和转移至关重要。而且，HLTF 被证明与 SRSF1 相互作用并有助于其蛋白质稳定性以激活 ERK/MAPK 信号通路并增强 HCC 生长和转移。此外，miR-511-5p在HCC组织中低水平表达，与HLTF负相关，调节HLTF表达。我们的研究表明，HLTF 在 HCC 进展中发挥致癌作用，并为 HCC 的诊断和治疗提供了新的生物标志物和治疗靶点。