Li Gao-Jie, Xiang Ying, Yang Ji-Yao, Weiskirchen Ralf, Feng Ruo, Zhai Wen-Long
Department of Histology and Embryology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
Examination Centre of the First Affiliated Hospital of Shihezi University, Shihezi, China.
J Gastrointest Oncol. 2024 Aug 31;15(4):1613-1626. doi: 10.21037/jgo-24-406. Epub 2024 Aug 15.
Cancer stem cells (CSCs) play a crucial role in tumor recurrence and metastasis, which are the primary causes of death in patients with hepatocellular carcinoma (HCC). Currently, no drug effectively blocks the recurrence and metastasis of liver cancer, leading to a poor prognosis for patients. To enhance treatment outcomes, there is an urgent need to investigate the molecular mechanisms behind the recurrence and progression of liver cancer, with the aim of identifying effective therapeutic targets. Targeting HCC stemness can improve the prognosis of patients with HCC. Abnormal spindle-like microcephaly-associated protein () plays a pivotal role in regulating neurogenesis and brain size, which is a centrosome protein. has been implicated in tumorigenesis and tumor progression, but its regulatory role in HCC stemness is not well understood. This study aims to investigate the role of in liver cancer stemness and elucidate its potential molecular mechanisms.
Bioinformatics analysis was used to study the expression of and its clinical significance in HCC. and assays were conducted to clarify the impact of knockdown on HCC cell stemness. The correlation between and the Wnt/β-catenin pathway was examined through analysis of online databases and experiments.
The bioinformatics analysis revealed significant upregulation of was significantly upregulated in HCC samples, with expression correlating with poor prognosis. experimental data confirmed elevated expression in HCC cells compared to normal hepatocytes. Knockdown of suppressed HCC cell growth, clone formation, spheroid formation, migration, invasion, and the expression of CSC markers and . This also inhibited the activation of the Wnt/β-catenin pathway. Reactivation of this pathway partially reversed the biological changes induced by knockdown in HCC cells. Additionally, data demonstrated that downregulation reduced the size and weight of xenografts in BALB/c mice, along with decreased expression of CSC markers.
These findings suggest that promotes HCC stemness and progression through the Wnt/β-catenin pathway. Targeting or the Wnt/β-catenin pathway may be a promising strategy to prevent HCC chemoresistance and recurrence, ultimately improving patient prognosis.
癌症干细胞（CSCs）在肿瘤复发和转移中起关键作用，而肿瘤复发和转移是肝细胞癌（HCC）患者死亡的主要原因。目前，尚无药物能有效阻断肝癌的复发和转移，导致患者预后较差。为提高治疗效果，迫切需要研究肝癌复发和进展背后的分子机制，以确定有效的治疗靶点。靶向肝癌干性可改善HCC患者的预后。异常纺锤样小头畸形相关蛋白（）在调节神经发生和脑大小中起关键作用，它是一种中心体蛋白。已被证明与肿瘤发生和肿瘤进展有关，但其在肝癌干性中的调节作用尚不清楚。本研究旨在探讨在肝癌干性中的作用，并阐明其潜在的分子机制。
采用生物信息学分析研究在HCC中的表达及其临床意义。进行和实验以阐明敲低对HCC细胞干性的影响。通过在线数据库分析和实验检测与Wnt/β-连环蛋白信号通路之间的相关性。
生物信息学分析显示，在HCC样本中显著上调，其表达与预后不良相关。实验数据证实，与正常肝细胞相比，HCC细胞中表达升高。敲低可抑制HCC细胞生长、克隆形成、球体形成、迁移、侵袭以及癌症干细胞标志物和的表达。这也抑制了Wnt/β-连环蛋白信号通路的激活。该信号通路的重新激活部分逆转了敲低诱导的HCC细胞生物学变化。此外，数据表明下调可减小BALB/c小鼠异种移植瘤的大小和重量，并降低癌症干细胞标志物的表达。
这些发现表明，通过Wnt/β-连环蛋白信号通路促进肝癌干性和进展。靶向或Wnt/β-连环蛋白信号通路可能是预防HCC化疗耐药和复发的有前景的策略，最终改善患者预后。
