Liu Jialong, Lu Yao, Zheng Bowen, Huang Deng, Song Juxian, Wang Baolin, Zheng Shuguo
Insititute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Department of Hepatobiliary, General Hospital of Tibet Military Command Area, Lhasa, Tibet, China.
Discov Oncol. 2024 Aug 20;15(1):360. doi: 10.1007/s12672-024-01243-2.
Hepatocellular carcinoma (HCC) stands as the third leading cause of cancer-related mortality globally. Metastasis, responsible for treatment failures, underscores the urgency to comprehend molecular drivers of invasion and migration. Central to the invasive and migratory processes underlying metastasis is the protein Talin1. However, the role and underlying mechanisms governing Talin1's involvement in HCC have remained elusive.
A total of 100 HCC specimens were collected from patients who underwent hepatectomy in our center. The expression level of talin1 was measured to evaluate the correlationship of talin1 and the development of HCC. In vitro and in vivo experiments were conducted to verify the characteristic of talin1 in HCC. RNA-seq and bioinformatics analysis were performed to identify the downstream signal pathway of talin1 and their impact on HCC development.
Here, we reported elevated levels of Talin1 mRNA and protein in HCC tissues. Meanwhile, downregulation of Talin1 significantly reduced the HCC cell proliferation and metastasis in vitro and in vivo. Furthermore, elevating NRG-1, a downstream target of Talin1, enhanced metastasis of HCC cells. More importantly, attenuation of Talin1 inhibited HCC progression through decreasing the stabilization of NRG1 mRNA, consequently regulating the expression of NRG1 and its involvement in mediating the PI3K/AKT pathway.
Taken together, Talin1 regulates cellular proliferation, metastasis, and invasiveness by modulating NRG1/PI3K/AKT axis, suggesting that Talin1 emerges as a promising candidate for treating HCC.
肝细胞癌（HCC）是全球癌症相关死亡的第三大主要原因。转移是导致治疗失败的原因，这凸显了理解侵袭和迁移分子驱动因素的紧迫性。Talin1蛋白是转移所涉及的侵袭和迁移过程的核心。然而，Talin1在HCC中的作用及潜在机制仍不清楚。
从在本中心接受肝切除术的患者中收集了100份HCC标本。检测talin1的表达水平，以评估talin1与HCC发生发展的相关性。进行体外和体内实验以验证talin1在HCC中的特性。进行RNA测序和生物信息学分析，以鉴定talin1的下游信号通路及其对HCC发展的影响。
在此，我们报告了HCC组织中Talin1 mRNA和蛋白水平升高。同时，Talin1的下调显著降低了体外和体内HCC细胞的增殖和转移。此外，提高Talin1的下游靶点NRG-1可增强HCC细胞的转移。更重要的是，Talin1的减弱通过降低NRG1 mRNA的稳定性来抑制HCC进展，从而调节NRG1的表达及其参与介导PI3K/AKT通路。
综上所述，Talin1通过调节NRG1/PI3K/AKT轴来调节细胞增殖、转移和侵袭性，这表明Talin1有望成为治疗HCC的候选药物。
