Effects of MCU-mediated Ca2+ Homeostasis on Ovarian Cancer Cell SKOV3 Proliferation, Migration and Transformation

Background: Atlas human proteomics database showed MCU as highly expressed in various tumor tissues, especially in ovarian cancer. Rare studies on the role of MCU and its regulation in ovarian cancer have been reported. Objective: The objective of this study was to determine role of MCU in ovarian cancer cell SKOV3 proliferation, migration, and transformation, and explore the possible mechanism. Methods: MCU siRNA on lentiviral particles were stably transfected into SKOV3 cells. CCK-8 assay was performed to analyze cell proliferation. Soft-agar colony formation assay was employed to evaluate tumorigenesis. Western blot and immunohistochemistry analyses were performed to evaluate the expression of MCU, MICU1 and phosphorylate of Akt in the ovarian cancer cell and tissue specimens. Scratch assay was combined with trans-well plates assay to detect the migration ability of cancer cells. The ROS production and Ca²⁺ expression were also determined. Results: MCU expression was significantly higher in ovarian cancer tissues than normal tissues. MCU silencing decreased SKOV3 cell proliferation, migration, and transformation. ROS production was decreased after MCU silencing, depending on disturbed Ca²⁺ homeostasis. MICU1 expression has been found to be decreased and phosphorylation of Akt increased when MCU was silenced. Conclusion: Down-regulation of MCU inhibited SKOV3 cell proliferation, migration, and transformation via disturbing Ca²⁺ homeostasis and decreasing ROS production. MICU1 and phosphorylation of Akt are associated with MCU-mediated ovarian cancer malignancy.