Abstract
Objective To investigate the effect of OA on proliferation, migration, and epithelial-mesenchymal transition (EMT) of ovarian cancer cells by inhibiting UNC5B and to study its mechanism. Methods TCGA database was used to analyze the expression of UNC5B in ovarian cancer and its relationship with prognosis. The expression of UNC5B in ovarian cancer cells was detected by qPCR assay. qRT-PCR was used to detect the changes of EMT markers after different treatments. CCK-8 assay was used to detect cell proliferation, transwell assay was used to evaluate cell migration, and clonogenesis assay was used to evaluate the effect of UNC5B on ovarian cancer cell proliferation. Meanwhile, the synergistic effect of OA on niraparib was evaluated. Results UNC5B was highly expressed in ovarian cancer, and its expression was negatively correlated with the prognosis of ovarian cancer patients. UNC5B was highly expressed in ovarian cancer cells SKOV3 and OVCA420 compared with normal ovarian epithelial cells. In addition, silencing UNC5B inhibits the proliferation, invasion, clonogenesis, and EMT processes of ovarian cancer cells. OA inhibits proliferation, invasion, and clonogenesis of ovarian cancer cells by inhibiting UNC5B and increases the antitumor activity of niraparib. Conclusion UNC5B acts as an oncogenic gene in ovarian cancer. OA inhibits ovarian cancer cell proliferation, migration, and EMT by targeting UNC5B and increases the antitumor effect of niraparib. UNC5B is expected to be a new potential therapeutic target for ovarian cancer. OA may be used as an antitumor drug and deserves further study.
Highlights
Ovarian cancer is one of the common malignant tumors of female reproductive organs [1,2,3]
Retrieval results showed that UNC5B expression was significantly elevated in ovarian cancer (426 serous ovarian cancer) compared with normal ovarian tissue (n 88) (Figure 1(a)). e relationship between the expression of UNC5B and overall survival (OS) time in ovarian cancer patients was analyzed by the GEPIA database
Immunohistochemical results were obtained from the Human Protein Atlas website. e expression of UNC5B in ovarian cancer and adjacent normal tissues was analyzed by qRT-PCR. e results showed that UNC5B was overexpressed in ovarian cancer tissues (Figure 1(e)). qRT-PCR results showed that UNC5B protein was highly expressed in CoC1, CAOV-3, OVCA420, and SKOV3 cells compared with IOSE-29 cells (Figure 1(f )). ese results suggest that high UNC5B expression is associated with poor prognosis in ovarian cancer patients, and patients with high UNC5B expression have a poor prognosis. ese results suggest that UNC5B may be associated with the occurrence and progression of ovarian cancer
Summary
Ovarian cancer is one of the common malignant tumors of female reproductive organs [1,2,3]. Epithelial to mesenchymal transition (EMT) is an important mechanism of tumor metastasis and invasion [6,7,8]. EMT refers to the transition of polar epithelial cells from tightly joined epithelial to mesenchymal forms under certain conditions. When EMT occurs, cells lose polarity, intercellular adhesion is weakened, and motor function is enhanced [9, 10]. Tumor cells with mesenchymal transformation are less sensitive to existing chemicals. Several studies have demonstrated that inhibition of the EMT process inhibits both metastasis and invasion of ovarian cancer cells [14,15,16]
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