CDC25C downregulation suppresses HCC growth via mitochondrial stress-induced autophagy and apoptosis.

[UNLABELLED] Cell division cyclin 25 C (CDC25C) functions as an antigen linked to hepatocellular carcinoma (HCC) and is vital for its diagnosis, treatment, and prognosis. However, the precise pathways underlying CDC25C-mediated inhibition of HCC growth remain incompletely understood. In this study, we created a CDC25C-downregulation model in AML12 and Hepa1-6 cell lines, complemented by a tumor xenograft in C57BL/6 mice. We evaluated the malignant biological behaviors and subcellular structural morphology of the CDC25C-downregulation model. Additionally, we quantified mitochondrial calcium levels, reactive oxygen species (ROS) concentrations, mitochondrial stress-related molecules, and autophagy-related proteins. Furthermore, we observed the morphological characteristics of apoptosis in CDC25C-downregulated cells, evaluated the apoptosis rate, and identified key molecules involved in the mitochondrial apoptosis pathway. Our findings indicated that the downregulation of CDC25C inhibited the proliferation, migration and invasion of HCC cells. Further analysis demonstrated that apoptosis in HCC cells was ultimately induced by CDC25C downregulation, which also triggered the mitochondrial stress response and autophagy. In contrast, normal hepatocytes exhibited the opposite effect, with the exception of autophagy. In summary, downregulation of CDC25C does not inhibit the growth of normal hepatocytes but inhibits HCC progression; its anti-HCC effect may be associated with the mitochondrial stress response as well as mitochondria-mediated autophagy and apoptosis.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1038/s41598-026-36351-2.