Cullin7 is a predictor of poor prognosis in breast cancer patients and is involved in the proliferation and invasion of breast cancer cells by regulating the cell cycle and microtubule stability.

Abstract

Cullin7 is the 'scaffold' of the cullin-RING-based E3 ligases which catalyze the final step of the ubiquitination cascade in eukaryotic organisms. Although one study has reported the involvement of cullin7 in the invasion and migration of breast cancer cells without further exploration of its mechanisms, the expression of cullin7 in breast cancer tissues and its clinical significance have not been reported. The present study evaluated cullin7 protein expression in malignant and benign breast tissues using immunochemistry, and further analyzed the association of positive cullin7 expression in breast cancer tissues with clinicopathological characteristics of breast cancer patients. Cullin7 expression was further silenced in breast cancer cells by siRNA and its functions and mechanisms in cell proliferation and invasion were investigated. The results showed that high cullin7 expression was significantly correlated with pathological stage(P=0.013) and lymph node metastasis (P=0.022) of breast cancer. Patients with high cullin7 expression had a shorter overall survival rate than those with low cullin7 expression(P=0.037). Silencing of cullin7 expression significantly inhibited the proliferation (P<0.05) and invasion (P<0.05), increased S1phase (P<0.05), but decreased G2phase (P<0.05) in MDA-MB-231 and BT549 cells. In addition, silencing of cullin7 expression decreased cyclinA, but increased p21 protein expression. Moreover, silencing of cullin7 expression altered the cell shape, caused disorder in microtubules, and increased the microtubule regeneration in MDA-MB-231 and BT549 cells. In conclusion, cullin7 is overexpressed in breast cancer tissues which is associated with the development and prognosis of breast cancer. Cullin7 is involved in the proliferation and invasion of breast cancer cells by regulating the cell cycle and microtubule stability.