肉碱棕榈酰转移酶 1C (CPT1C) 是一种通过调节线粒体功能和脂质代谢来调节肿瘤细胞增殖和代谢的酶。实体瘤中常见的缺氧通过调节肿瘤细胞的代谢重编程促进胰腺癌的增殖和进展。迄今为止，CPT1C对缺氧肿瘤细胞的代谢调节及其上游机制仍知之甚少。阴阳1（YY1）是胰腺肿瘤发生的关键癌基因，并作为参与多种代谢过程的转录因子。本研究旨在阐明缺氧条件下YY1和CPT1C之间的关系，并探讨它们在缺氧诱导的肿瘤细胞增殖和代谢改变中的作用。结果显示，缺氧条件下 PANC-1 细胞的增殖和代谢增强，细胞生长增加、细胞 ATP 水平增加、线粒体膜电位上调和脂质含量降低。有趣的是，敲低 YY1 或 CPT1C 会抑制缺氧诱导的快速细胞增殖和旺盛的细胞代谢。重要的是，我们首次报道YY1直接激活CPT1C的转录，并阐明CPT1C是YY1的新靶基因。此外，通过将YY1 siRNA转染至CRISPR/Cas9-CPT1C敲除PANC-1细胞，发现YY1和CPT1C可以协同调节缺氧细胞的增殖和代谢。综上所述，这些结果表明YY1-CPT1C轴可能成为干预胰腺癌增殖和代谢的新靶点。版权所有©2024。由Elsevier Inc.出版。

Carnitine palmitoyltransferase 1C (CPT1C) is an enzyme that regulates tumor cell proliferation and metabolism by modulating mitochondrial function and lipid metabolism. Hypoxia, commonly observed in solid tumors, promotes the proliferation and progression of pancreatic cancer by regulating the metabolic reprogramming of tumor cells. So far, the metabolic regulation of hypoxic tumor cells by CPT1C and the upstream mechanisms of CPT1C remain poorly understood. Yin Yang 1 (YY1) is a crucial oncogene for pancreatic tumorigenesis and acts as a transcription factor that is involved in multiple metabolic processes. This study aimed to elucidate the relationship between YY1 and CPT1C under hypoxic conditions and explore their roles in hypoxia-induced proliferation and metabolic alterations of tumor cells. The results showed enhancements in the proliferation and metabolism of PANC-1 cells under hypoxia, as evidenced by increased cell growth, cellular ATP levels, up-regulation of mitochondrial membrane potential, and decreased lipid content. Interestingly, knockdown of YY1 or CPT1C inhibited hypoxia-induced rapid cell proliferation and vigorous cell metabolism. Importantly, for the first time, we reported that YY1 directly activated the transcription of CPT1C and clarified that CPT1C was a novel target gene of YY1. Moreover, the YY1 and CPT1C were found to synergistically regulate the proliferation and metabolism of hypoxic cells through transfection with YY1 siRNA to CRISPR/Cas9-CPT1C knockout PANC-1 cells. Taken together, these results indicated that the YY1-CPT1C axis could be a new target for the intervention of pancreatic cancer proliferation and metabolism.Copyright © 2024. Published by Elsevier Inc.