S100A7 Regulates Ovarian Cancer Cell Metastasis and Chemoresistance Through MAPK Signaling and Is Targeted by miR-330-5p.DNA Cell Biol. 2018 May; 37(5):491-500.DC
Epithelial ovarian cancer (EOC) is the most common cause of gynecological cancer-associated death. The high mortality rate is largely due to early stage metastasis and posttreatment recurrence. Identifying crucial regulators of EOC cells as well as ways to target them promises to improve the disease's prognosis. The S100 calcium-binding protein A7 (S100A7) has been shown to promote cell proliferation, migration, invasion, and tumor metastasis. In this study, we have investigated the role that S100A7 plays in regulating EOC cells. We have also identified the microRNA protein miR-330-5p, a known suppressor of oncogenesis and chemoresistance, as an inhibitor of S100A7 activity. We employed both fresh EOC tissue specimens as well as EOC cell lines Caov3 and SKOV3. S100A7 levels were analyzed using quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry. siRNA was used to knockdown S100A7. Cell proliferation, colony formation, and Transwell migration and invasion assays were performed on EOC cell lines with and without cisplatin treatment. TargetScan was used to identify miR-330-5p as a regulator of S100A7. Luciferase reporter plasmids were constructed with either the wild-type or mutant S100A7 3'UTR to determine the effect of miR-330-5p on S100A7. S100A7 was significantly overexpressed in human EOC tissue specimens and EOC cell lines Caov3 and SKOV3. Knocking down S100A7 reduced EOC cell proliferation, migration, and invasion. Furthermore, S100A7 knockdown cells demonstrated increased sensitivity to the chemotherapeutic cisplatin. Finally, miR-330-5p was shown to target the S100A7 3'UTR and to reduce EOC cell growth by inhibiting S100A7 expression. As a regulator of EOC cell proliferation, metastasis, and chemoresistance, S100A7 represents a potential prognostic biomarker for EOC as well as a treatment target. Because miR-330-5p functions as an inhibitor of EOC cell growth and S100A7 expression, it promises to improve EOC outcomes. Further research into the clinical significance of both S100A7 and miR-300-5p is warranted.