Cell division cyclin 25C knockdown inhibits hepatocellular carcinoma development by inducing endoplasmic reticulum stress.

Background: Cell division cyclin 25C () is a protein that plays a critical role in the cell cycle, specifically in the transition from the G2 phase to the M phase. Recent research has shown that could be a potential therapeutic target for cancers, particularly for hepatocellular carcinoma (HCC). However, the specific regulatory mechanisms underlying the role of in HCC tumorigenesis and development remain incompletely understood.

Aim: To explore the impact of on cell proliferation and apoptosis, as well as its regulatory mechanisms in HCC development.

Methods: Hepa1-6 and B16 cells were transduced with a lentiviral vector containing shRNA interference sequences (LV- shRNA) to knock down . Subsequently, a xenograft mouse model was established by subcutaneously injecting transduced Hepa1-6 cells into mice to assess the effects of knockdown on HCC development . Cell proliferation and migration were evaluated using a Cell Counting Kit-8 cell proliferation assays and wound healing assays, respectively. The expression of endoplasmic reticulum (ER) stress-related molecules (glucose-regulated protein 78, X-box binding protein-1, and C/EBP homologous protein) was measured in both cells and subcutaneous xenografts using quantitative real-time PCR (qRT-PCR) and western blotting. Additionally, apoptosis was investigated using flow cytometry, qRT-PCR, and western blotting.

Results: was stably suppressed in Hepa1-6 and B16 cells through LV- shRNA transduction. A xenograft model with knockdown was successfully established and that downregulation of expression significantly inhibited HCC growth in mice. knockdown not only inhibited cell proliferation and migration but also significantly increased the ER stress response, ultimately promoting ER stress-induced apoptosis in HCC cells.

Conclusion: The regulatory mechanism of in HCC development may involve the activation of ER stress and the ER stress-induced apoptosis signaling pathway.