Abstract
Ovarian cancer is the leading cause of death in gynecological malignancies worldwide. Our previous studies have proved that metformin inhibited the proliferation and invasion of ovarian cancer in vitro and in vivo. However, the underlying mechanisms have not been fully elucidated. Immunohistochemistry was performed to detect the expression of TRIM37, Ki-67 and MMP-9 in ovarian cancer and normal tissues. The influence of TRIM37 on the proliferation and invasion of ovarian cancer cells were verified by the RTCA proliferation test, colony formation test and Transwell assay. Western blot and immunoprecipitation were employed to detect the expression of NF-κB pathway and the interaction between TRIM37 and TRAF2. Ubiquitination detection was done to detect the ubiquitination level of TRAF2. The present study revealed that TRIM37 expression was significantly increased in ovarian cancer tissues compared with that in normal control tissues, and its overexpression was closely associated with proliferation and metastasis. Metformin inhibited the NF-κB signaling pathway via downregulating TRIM37. Also, metformin inhibited the ubiquitination of TRAF2 induced by TRIM37-overexpression. Metformin inhibits the proliferation and invasion of ovarian cancer cells by suppressing TRIM37-induced TRAF2 ubiquitination.
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