Abstract
BACKGROUND: Ovarian cancer, a prevalent cause of cancer-related mortality among gynecological cancers, still lacks a clear understanding of its pathogenesis. In this study, our objective was to investigate the functional roles and pathogenic mechanisms of HADHA in ovarian cancer. METHODS: We utilized an ovarian cancer tissue microarray and three ovarian cancer cell lines (HO-8910, A2780, and SK-OV-3) for our analysis. Lentiviral-mediated short hairpin RNA (shRNA) was employed to interfere with HADHA expression in ovarian cancer cells. Various cellular events associated with tumor development were assessed using techniques such as Celigo cell counting assay, wound healing assay, Transwell assay, and flow cytometry analysis. Additionally, xenograft tumor models were developed to visualize the impacts of HADHA/CDK1 on ovarian cancer progression. RESULTS: Our data revealed significant HADHA overexpression in both ovarian cancer tissues and cell lines. Patients with elevated HADHA levels tended to experience poor survival outcomes. Moreover, HADHA upregulation correlated with several pathological parameters, including pathological stage, tumor size, tumor infiltrate, metastasis, and recurrence. Loss-of-function experiments targeting HADHA demonstrated that its suppression in ovarian cancer cells hindered cell growth and migration, while promoting apoptosis. To elucidate the underlying mechanism by which HADHA regulates ovarian cancer, we identified CDK1 as a target of HADHA. HADHA upregulated CDK1 expression by inhibiting its ubiquitination-dependent proteasomal degradation. Significantly, the overexpression of CDK1 reversed the impaired cell development caused by HADHA depletion, both in vitro and in vivo. CONCLUSION: Our study highlights the involvement of HADHA in ovarian cancer tumorigenesis and suggests its potential as a promising prognostic marker in ovarian cancer. Through its regulation of CDK1, HADHA influences critical cellular processes in ovarian cancer, providing insights into its pathogenic mechanism.