DEPDC1 Promotes Cell Growth and Reduces Radiosensitivity of Cervical Cancer Cells

Background: Cervical cancer (CC) is one of the prevalent cancers among females. The DEP domain containing 1 (DEPDC1) has been found to play a crucial role in the progression of cancers by promoting tumorigenesis. However, the regulatory role of DEPDC1 in CC progression remains unclear. Therefore, this study aimed to investigate the regulatory functions of DEPDC1, and its associated pathway in the progression of CC. Methods: Initially, using the UALCAN database, the higher expression level of DEPDC1 was confirmed in both CC and normal tissues. However, the expression levels of proteins were evaluated using immunohistochemistry (IHC) assay and western blot analysis. Moreover, the viability and proliferation capabilities of the cells were determined using cell counting kit-8 (CCK-8) and 5-ethynyl-2 ' -deoxyuridine (EdU) assays, respectively. Furthermore, the radiosensitivity of CC cells was evaluated using colony formation assay. The level of gamma-H2A histone family member X (gamma-H2AX) was assessed within the small interfering RNA-negative control (si-NC), si-DEPDC1#1, si-NC+4 Gray (Gy), and si-DEPDC1#1+4 Gy groups using Immunofluorescence (IF) assay. The cell apoptosis was examined in the si-NC, si-DEPDC1#1, si-NC+4 Gy, and si-DEPDC1#1+4 Gy groups using flow cytometry. Additionally, in vivo assays were utilized to determine the growth of tumors within the short hairpin RNA-negative control (sh-NC), sh-DEPDC1, ionizing radiation (IR), and IR+sh-DEPDC1 groups of mice. Results: It was observed that CC patients with higher DEPDC1 expression level showed poor prognosis. The expression of DEPDC1, both at mRNA and protein level, was significantly elevated in CC tissues (p < 0.05). Moreover, silencing of DEPDC1 suppressed tumor cell growth and proliferation in CC (p < 0.05). Furthermore, radiosensitivity of CC cells was found at 0, 2, 4, 6 Gray-infrared radiation treatment (p < 0.05). However, it was observed that the radiosensitivity of both HeLa-radiation resistant (RR) and SiHa-RR cells was significantly enhanced following DEPDC1 knockdown (p < 0.05). Similarly, inhibition of DEPDC1 enhanced radiation-induced cell apoptosis in CC (p < 0.05) and retarded the forkhead box M1 (FOXM1)/ubiquitin-like plant homeodomain (PHD) and RING finger domain containing 1 (UHRF1) pathway, thereby influencing CC progression (p < 0.05). Additionally, the knockdown of DEPDC1 retarded tumor growth and promoted radiosensitivity in vivo (p < 0.05). Conclusion: The DEPDC1 accelerated cell growth and reduced radiosensitivity in CC by modulating the FOXM1/UHRF1 pathway. These findings suggest that DEPDC1 might be a potential bio-target for the treatment of CC.