Objective:
Ovarian cancer is one of the most common gynecological
malignancies worldwide, and its mortality rate ranks first among gynecologic
cancers.
Ceramide synthases are closely related to
cancer development. In this study, we investigated the role of
ceramide synthase 6 (CerS6) in the development of serous
ovarian cancer. Methods: Expression of CerS6 in cancerous and healthy ovarian tissue was assessed by database analysis and immunohistochemistry. The biological role of CerS6 in serous
ovarian cancer cells was assessed by CerS6 knockdown followed by cell counting, colony formation, transwell migration, wound healing, and flow cytometry assays and measurement of
tumor proliferation in nude mice. Signaling pathway components were analyzed by Western blotting. Gene enrichment was analyzed by GSEA and R, and
RNA sequencing was used to compare the transcriptomes of serous
ovarian cancer cells with and without CerS6 knockdown. Results: High CerS6 expression in
ovarian cancer tissues was closely related to poor prognosis. Knockdown of CerS6 inhibited serous
ovarian cancer cell proliferation, invasion, and
metastasis and promoted their apoptosis. In addition, CerS6 knockdown increased the proportion of serous
ovarian cancer cells in G2/M phase. CerS6 regulates cell cycle through the AKT/mTOR/4EBP1 signaling pathway, which affects cell proliferation and
metastasis. The GSEA, R, and
RNA sequencing analyses showed that knocking down CerS6 significantly affects cell cycle in serous
ovarian cancer cells. Conclusions: CerS6 may have an oncogenic role in
ovarian cancer and may represent a new prognostic marker and therapeutic target for serous
ovarian cancer.