RAD51C, located on chromosome 17q23, is a susceptibility gene for ovarian cancer. It belongs to the homologous recombination repair gene family and plays a crucial role in tumor occurrence, development, and prognosis through homologous recombination repair [6]. Overexpression or mutation of RAD51C can disrupt homologous recombination repair, leading to genomic instability [7, 8] and ultimately resulting in tumorigenesis. As one of the key proteins in the homologous recombination repair pathway, RAD51C is closely associated with Fanconi anemia and various malignant tumors, including breast cancer, pancreatic cancer, and prostate cancer [9, 10, 11]. Our previous studies at the protein and cellular levels have demonstrated a significant overexpression of the RAD51C protein in tissues of ovarian cancer, which is related to pathological type, clinical stage, pathological classification, and prognosis, but not associated with patient age. Knocking down the RAD51C gene in human ovarian cancer cell lines has been shown to inhibit the proliferation and migration of ovarian cancer cells while promoting apoptosis, highlighting the close relationship between RAD51C and the occurrence and development of ovarian cancer [12, 13].
Vascular endothelial growth factor (VEGF) is a glycoprotein with vascular permeability activity [14], with a molecular weight of 35–45 kDa [15]. The VEGF gene is located on chromosome 6p21.3 [16]. As a type of pro-angiogenic cytokine, VEGF is expressed in endothelial cells (EC), stromal cells, tumor cells, and some inflammatory cells and must bind specifically to its receptor to exert its effects [17]. After binding to the receptor, VEGF causes receptor self-phosphorylation, activates signal transduction pathways, and exerts biological effects [18]. VEGF is a powerful angiogenic factor, and the occurrence and development of malignant tumors cannot be separated from neovascularization (angiogenesis). The process of neovascularization is very complex, and the newly generated blood vessels have specific structures. The signal of vascular generation can stimulate tumor cells, enhance their invasion and metastasis ability, and as the tumor grows, its demand for various nutrients continues to increase. The continuous generation of new blood vessels can meet the metabolic needs of tumor cells, so neovascularization is crucial for tumor growth [19, 20] and is a necessary condition for the occurrence and development of malignant tumors [21]. It plays a crucial role in angiogenesis, essential for tumor growth, invasion, and metastasis of malignant tumors [22]. Targeted drugs against VEGF-mediated angiogenesis are necessary for targeted therapy for malignant tumors [23, 24]. They are expected to provide new treatment options to reduce tumor recurrence rates and improve survival rates.
Neuropilin-2 (NRP2) is a receptor for lymphatic endothelial cells belonging to the family of single-pan transmembrane glycoproteins. It is widely expressed in tumor tissues that promote tumor metastasis by binding to lymphatic endothelial cell growth factors. Multiple studies by Borkowetz, Moriarty, and others have shown that NRP2 enhances tumor cell proliferation, invasion, and migration, thereby promoting tumor progression and lymphatic metastasis [25, 26, 27, 28, 29]. Jauhiainen et al. [30] and Favier et al. [31] also showed that NRP2 enhances VEGF-induced survival and migration of endothelial cells. The occurrence and development of malignant tumors are closely related to the interaction between VEGF and NRP2, which promotes tumor invasion and metastasis. Studies have also shown that NRP-2 is expressed in various malignant tumor tissues, such as breast cancer, colon cancer, and pancreatic cancer [32 ,33], and is also related to chemotherapy with tumor cell resistance to cisplatin [34]. It plays a vital role in regulating tumor cell proliferation, migration, and apoptosis, making it a potential target for targeted therapy of malignant tumors [35].
In this study, tumor formation of ovarian cancer cells in animals was observed by interfering with RAD51C gene, and differences in protein expression of RAD51C, VEGF and NRP-2 were detected in tumors. The results showed that interference with RAD51C gene of ovarian cancer cells could inhibit tumor growth, although it did not achieve significant inhibition of tumor growth, it could not be ruled out that it was caused by internal and external factors of the experiment itself, and subsequent experiments will be strengthened. but the expressions of RAD51C protein,NRP-2 protein and VEGF protein were significantly reduced. Therefore, it can be concluded that RAD51C, VEGF and NRP-2 may be related to the occurrence and development of ovarian cancer. Then, what is the possible relationship between RAD51C, VEGF and NRP-2? A possible hypothesis is that the abnormal function of RAD51C may indirectly affect the expression or activity of VEGF and NRP-2. For example, DNA repair disorders can lead to genomic instability, which in turn activates certain signaling pathways that may ultimately regulate the expression of VEGF and NRP-2. In addition, the interaction of RAD51C with certain tumor suppressor genes or oncogenes may also indirectly affect the functional expression or activity of VEGF and NRP-2. Second, given the critical role of VEGF and NRP-2 in angiogenesis and tumor development, we can speculate that they may be regulated by upstream signaling pathways. These upstream signaling pathways may include factors and signaling molecules associated with tumorigenesis, cell proliferation, and angiogenesis. These factors and signaling molecules may interact with RAD51C through some mechanism, thereby affecting the expression and function of VEGF and NRP-2.
In summary, the relationship between RAD51C, VEGF and NRP-2 is a topic worthy of further study. By following up with further studies to reveal the mechanism of their interaction, we may be able to provide new ideas and strategies for the treatment and prevention of tumors.