Department of Medicine II, Section Molecular Hepatology, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
Current address: Department of Molecular and Integrative Physiology, Rogel Cancer Centre, University of Michigan, Ann Arbor, MI, 48109, USA.
BMC Cancer. 2021 Sep 8;21(1):1006. doi: 10.1186/s12885-021-08637-3.
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death. Paired related homeobox 1 (PRRX1) is a transcription factor that regulates cell growth and differentiation, but its importance in HCC is unclear.
We examined the expression pattern of PRRX1 in nine microarray datasets of human HCC tumour samples (n > 1100) and analyzed its function in HCC cell lines. In addition, we performed gene set enrichment, Kaplan-Meier overall survival analysis, metabolomics and functional assays.
PRRX1 is frequently upregulated in human HCC. Pathway enrichment analysis predicted a direct correlation between PRRX1 and focal adhesion and epithelial-mesenchymal transition. High expression of PRRX1 and low ZEB1 or high ZEB2 significantly predicted better overall survival in HCC patients. In contrast, metabolic processes correlated inversely and transcriptional analyses revealed that glycolysis, TCA cycle and amino acid metabolism were affected. These findings were confirmed by metabolomics analysis. At the phenotypic level, PRRX1 knockdown accelerated proliferation and clonogenicity in HCC cell lines.
Our results suggest that PRRX1 controls metabolism, has a tumour suppressive role, and may function in cooperation with ZEB1/2. These findings have functional relevance in HCC, including in understanding transcriptional control of distinct cancer hallmarks.
肝细胞癌（HCC）是癌症相关死亡的主要原因。配对相关同源盒 1（PRRX1）是一种转录因子，可调节细胞生长和分化，但它在 HCC 中的重要性尚不清楚。
我们检查了 9 个人类 HCC 肿瘤样本微阵列数据集（n>1100）中 PRRX1 的表达模式，并分析了其在 HCC 细胞系中的功能。此外，我们进行了基因集富集、Kaplan-Meier 总生存分析、代谢组学和功能测定。
PRRX1 在人类 HCC 中经常上调。通路富集分析预测 PRRX1 与焦点黏附和上皮间质转化之间存在直接相关性。PRRX1 高表达和 ZEB1 低表达或 ZEB2 高表达显著预测 HCC 患者的总生存更好。相反，代谢过程呈负相关，转录分析显示糖酵解、三羧酸循环和氨基酸代谢受到影响。代谢组学分析证实了这些发现。在表型水平上，PRRX1 敲低加速了 HCC 细胞系的增殖和集落形成。
我们的结果表明，PRRX1 控制代谢，具有肿瘤抑制作用，并且可能与 ZEB1/2 合作发挥作用。这些发现对 HCC 具有功能相关性，包括理解不同癌症特征的转录控制。
