Chai Bao, Zhang Anhong, Liu Yang, Zhang Xi, Kong Pengzhou, Zhang Zhuowei, Guo Yarong
Department of Gastroenterology, Shanxi Bethune Hospital, Shanxi Academy of Medical sciences, TongilShanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Department of Surgery, The First Affiliated Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
J Cell Mol Med. 2024 Dec;28(23):e70245. doi: 10.1111/jcmm.70245.
Krüppel-like factor 7 is a transcriptional activator and acts as an oncogene in human cancers, including hepatocellular carcinoma (HCC). Tryptophan metabolism is important for HCC cell proliferation, metastasis, and invasion. It is unclear whether KLF7 could regulate Trp metabolism in HCC. In this study, we found that Trp metabolism was suppressed in HCC cells with KLF7 knockdown. The mRNA and protein levels of SLC1A5, SLC7A5, and TPH1, as well as the content of Trp and serotonin, were reduced after KLF7 knockdown, and were potentiated following KLF7 overexpression. Increasing the content of serotonin could restore the malignancy of tumour cells in vitro and tumour growth in vivo. Conversely, decreasing the content of serotonin suppressed HCC cell proliferation. The binding activity of KLF7 was on the promoter of SLC1A5, and KLF7 positively regulated the expression of SLC1A5. KLF7 contributed to the proliferation and migration of HCC cells by up-regulation of SLC1A5. Collectively, KLF7 promotes the progression of HCC through regulating Trp metabolism. The newly identified axis of KLF7/ SLC1A5 in HCC could represent a potential target for HCC therapy.
Krüppel样因子7是一种转录激活因子，在包括肝细胞癌（HCC）在内的人类癌症中作为癌基因发挥作用。色氨酸代谢对肝癌细胞的增殖、转移和侵袭很重要。目前尚不清楚KLF7是否能调节肝癌中的色氨酸代谢。在本研究中，我们发现KLF7敲低的肝癌细胞中色氨酸代谢受到抑制。KLF7敲低后，SLC1A5、SLC7A5和TPH1的mRNA和蛋白水平以及色氨酸和血清素的含量均降低，而KLF7过表达后则增强。增加血清素含量可恢复体外肿瘤细胞的恶性程度和体内肿瘤生长。相反，降低血清素含量可抑制肝癌细胞增殖。KLF7的结合活性位于SLC1A5的启动子上，KLF7正向调节SLC1A5的表达。KLF7通过上调SLC1A5促进肝癌细胞的增殖和迁移。总体而言，KLF7通过调节色氨酸代谢促进肝癌进展。肝癌中新发现的KLF7/SLC1A5轴可能代表肝癌治疗的潜在靶点。
