TRIM65 Promotes Malignant Cell Behaviors in Triple-Negative Breast Cancer by Impairing the Stability of LATS1 Protein

Abstract

TNBC is a malignant tumor that easily relapses and metastasizes, with a poor prognosis in women. Ubiquitination plays a key role in promoting the tumor process. In various tumors, TRIM65 can affect malignant biological tumor behavior by ubiquitination of related proteins. We aimed to investigate TRIM65 expression in TNBC and whether it promotes malignant biological behavior in TNBC cells using Cell Counting Kit-8, colony formation, and transwell assays. Mechanically, we confirmed that TRIM65 promoted TNBC invasion and metastasis by ubiquitination of LATS1 protein through Co-IP, CHX, and endogenous ubiquitination experiments. The expression of TRIM65 was abnormally high and accelerated the proliferation, invasion, and migration of MDA-MB-231 and MDA-MB-453 cells. In vivo animal experiments also revealed that TRIM65 accelerated TNBC cell proliferation. Mechanistically, TRIM65 degraded LATS1 protein expression through ubiquitination in the Co-IP, CHX, and endogenous ubiquitination experiments. Rescue assays confirmed that TRIM65 degraded LATS1 protein expression, accelerating the proliferation, invasion, and migration ability of TNBC cells. Our results show that TRIM65 is upregulated in TNBC, and TRIM65 degrades LATS1 protein expression through ubiquitination and promotes malignant biological behavior in TNBC cells. TRIM65 may play an important role as a new oncogene in TNBC.

TRIM65 promotes renal cell carcinoma through ubiquitination and degradation of BTG3

“…Being a known E3 ligase, TRIM65 was involved in the regulation of some cell activities and related diseases mainly via the degradation of its specific substrates. As reported, TRIM65 functioned as an oncogene in various tumors, including breast cancer [ 32 ], gastric cancer [ 24 ], cervical cancer [ 23 ], pituitary tumors [ 33 ], etc. No study to date has mentioned the effects of TRIM65 on RCC.…”