Contribution of sphingomyelin phosphodiesterase acid-like 3B to the proliferation, migration, and invasion of ovarian cancer cells

Baozhi Song; Yu Jiang; Ying Lin; Jiahua Liu; Yatao Jiang

doi:10.21037/tcr-24-309

Contribution of sphingomyelin phosphodiesterase acid-like 3B to the proliferation, migration, and invasion of ovarian cancer cells

Transl Cancer Res. 2024 Apr 30;13(4):1954-1968. doi: 10.21037/tcr-24-309. Epub 2024 Apr 25.

Authors

Baozhi Song¹, Yu Jiang¹, Ying Lin², Jiahua Liu¹, Yatao Jiang³

Affiliations

¹ Department of Gynecology, Shengli Clinical Medical College of Fujian Medical University & Fujian Provincial Hospital, Fuzhou, China.
² Department of Pathology, Shengli Clinical Medical College of Fujian Medical University & Fujian Provincial Hospital, Fuzhou, China.
³ Department of Obstetrics, Shengli Clinical Medical College of Fujian Medical University & Fujian Provincial Hospital, Fuzhou, China.

Abstract

Background: Cancer has the highest mortality rate among gynecological cancers and poses a serious threat to women's lives. However, the treatment options for ovarian cancer are still limited, and exploring effective targeted biomarkers is particularly important for predicting and treating ovarian cancer. Therefore, it is necessary to explore the molecular mechanisms of the occurrence and development of ovarian cancer.

Methods: This investigation encompassed the analysis of gene expression profiles, measurement of transcription levels of potential target genes in peripheral blood samples from ovarian cancer patients and characterization of the ovarian cancer-related secretory protein sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B). Through bioinformatics analysis, potential target genes were identified, and their association with overall survival (OS) and progression-free survival (PFS) in ovarian cancer patients was assessed utilizing relevant databases. Subsequently, differences in target gene expression in ovarian cancer tissue samples were validated through protein blotting and quantitative real-time PCR (qRT-qPCR). Cell proliferation assays using the cell count kit-8 (CCK-8) method, as well as transwell chamber assay and pre coated matrix gel chamber assay were employed to elucidate the role of SMPDL3B in ovarian cancer cell migration and invasion.

Results: This study revealed a substantial upregulation of SMPDL3B in the serum of ovarian cancer patients, correlating with an unfavorable prognosis. High SMPDL3B expression was linked not only to increased proliferation of ovarian cancer cells, but also enhanced migration and invasion. Remarkably, the knockdown the human alkaline ceramidase 2 (ACER2) gene in cancer cells with heightened SMPDL3B expression significantly inhibited cell proliferation, migration, and invasion induced by SMPDL3B activation (P<0.05), highlighting the functional interplay between ACER2 and SMPDL3B in ovarian cancer.

Conclusions: In summary, this study proposes SMPDL3B as a prognostic marker for ovarian cancer, with implications for potential therapeutic intervention targeting the ACER2-SMPDL3B axis.

Keywords: ACER2-SMPDL3B axis; Ovarian cancer; sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B).