Cervical cancer (CC) is the most frequently diagnosed genital tract cancer in females worldwide. Rac GTPase-activating protein 1 (RacGAP1) is one of the specific GTPase-activating proteins. As a novel tumor protooncogene, overexpression of RacGAP1 was related to the occurrence of various tumors, but its function in CC is still unclear. In this study, bioinformatics analyses showed that RacGAP1 might be a key candidate gene in the progression of CC. RacGAP1 was significantly overexpressed in CC tissues. High RacGAP1 expression was positively associated with poor prognosis. Downregulating RacGAP1 significantly inhibited the proliferation, migration, and invasion of CC cells, while overexpressing RacGAP1 had the opposite effects. Further research showed that miR-192, which plays as a tumor suppressor in CC, was identified as a downstream target of RacGAP1 in CC cells. miR-192 inhibition could partially rescue the decrease in cell proliferation, migration, and invasion caused by RacGAP1 downregulation. In opposite, miR-192 overexpression could decrease the promotion of malignant progression caused by RacGAP1 upregulation. Mechanism studies revealed that RacGAP1 could regulate the expression and phosphorylation of c-Jun, which was the component of AP-1, via miR-192 and p-JNK separately. These findings suggested that RacGAP1 promoted tumorigenicity, migration, and invasion of CC. Therefore, it represented a potential novel prognostic marker in CC and may probably be a therapeutic target.

Purpose Osteosarcoma is the most common primary bone tumor with poor prognosis, characterized by high recurrence and metastasis. Recent studies show that Reptin is overexpressed in several malignant tumors and is required for tumorigenesis. Reptin is thought to be involved in chromatin remodeling and DNA damage repair. However, the biological function and the molecular mechanism of Reptin in osteosarcoma are still not fully understood. Methods The expression of Reptin was detected in 59 osteosarcoma and 35 non-neoplastic bone specimens by immunohistochemistry. Kaplan -Meier curves was used to evaluate the prognostic significance of Reptin. Then we knockdown the expression of Reptin in Saos-2 and U2OS cells. MTT, Edu assay, flow cytometry, wound-healing and transwell assays were performed to examine the influences of Reptin expression on cell proliferation, cell cycle, migration and invasion. We further conducted co-immunoprecipitation experiments to explore the relationship between Reptin and DNA-PKcs. Finally, we determined the role of Reptin on DNA damage repair and chemosensitivity of cisplatin. Results We verified that high expression of Reptin was closely associated with tumor differentiation, Enneking stage and metastasis. Patients with Reptin-positive staining exhibited a significantly decreased overall survival. Additionally, we found that Reptin deleption inhibited the proliferation, invasion of osteosarcoma cells and caused G1 arrest. Furthermore, we discovered that Reptin participate in DNA damage repair through interaction with DNA-PKcs, inhibition of Reptin expression in osteosarcoma cells enhances cisplatin sensitivity by aggravating DNA damage. Conclusions In summary, we revealed that Reptin plays a crucial role in tumor growth and may serve as an attractive therapeutic target for osteosarcoma.