Han Yinglin, Wu Kaimin, Peng Xin, Fu Yinkun, Li Wenyan, Ma Jing, Jiang He, Zhao Xu-Yun
Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Physiol Rep. 2024 Dec;12(24):e70160. doi: 10.14814/phy2.70160.
Hepatocellular carcinoma (HCC) is a widely prevalent type of primary liver cancer. However, strategies for pretumor intervention are still limited. In this study, a liver-specific Zbtb7b knockout mouse model was used to evaluate the role of Zbtb7b in metabolic dysfunction-associated steatotic liver disease (MASLD)-related HCC development. We revealed that Zbtb7b was compensatively increased and restricted lipid deposition in the liver during MASLD progression, which protects against MASLD-related HCC initiation. Mechanistically, Zbtb7b suppresses the expression of the long noncoding RNA H19 to attenuate hepatic de novo lipogenesis and increase fatty acid oxidation, thereby preventing lipid accumulation in hepatocytes. As a result, the proliferation and migration abilities of HCC cells are reduced. Overall, we demonstrated that Zbtb7b serves as a tumor suppressor at an early stage of HCC, thus providing a promising target for the treatment of HCC at a premalignant stage.
肝细胞癌（HCC）是一种广泛流行的原发性肝癌类型。然而，肿瘤前干预策略仍然有限。在本研究中，使用肝脏特异性Zbtb7b基因敲除小鼠模型来评估Zbtb7b在代谢功能障碍相关脂肪性肝病（MASLD）相关HCC发生发展中的作用。我们发现，在MASLD进展过程中，Zbtb7b代偿性增加并限制肝脏中的脂质沉积，这可预防MASLD相关HCC的发生。机制上，Zbtb7b抑制长链非编码RNA H19的表达，以减弱肝脏从头脂肪生成并增加脂肪酸氧化，从而防止脂质在肝细胞中积累。结果，HCC细胞的增殖和迁移能力降低。总体而言，我们证明Zbtb7b在HCC早期阶段起肿瘤抑制作用，从而为癌前阶段HCC的治疗提供了一个有前景的靶点。
