Effects of MCU mediated Ca2+ homeostasis on ovarian cancer cell SKOV3 proliferation, migration and transforming

Abstract

Background: Atlas human proteomics database showed MCU was highly expressed in various tumor tissues, especially in ovarian cancer. Rare studies about the role of MCU and its regulation in ovarian cancer was reported. Objective: The objective of this study was to determine role of MCU in ovarian cancer cell SKOV3 proliferation, migration, and transforming and to 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 the tumorigenesis. Western blot and immunohistochemistry analyses were performed to evaluate the expression of MCU, MICU1 and phosphorylate of Akt in 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+ were also determined. Results: MCU expression was significantly higher in ovarian cancer tissues than normal tissues. MCU silencing decreased SKOV3 cell proliferation, migration, and transforming. ROS production was decreased after MCU silencing, depending on disturbed Ca2+ homeostasis. MICU1 expression decreased and phosphorylation of Akt increased when MCU silenced. Conclusions: Down-regulation of MCU inhibited SKOV3 cell proliferation, migration, and transforming via disturbing Ca2+ homeostasis and decreasing ROS production. MICU1and phosphorylation of Akt was associated with MCU -mediated ovarian cancer malignancy.