Reduced PDZRN4 promotes breast cancer progression and predicts poor prognosis

Breast cancer (BC) is one of the most lethal types of cancer throughout the world due its proliferation and invasion. PDZ domain containing ring finger 4 (PDZRN4) belongs to the LNX family, which has E3 ubiquitin ligase activity and is involved in the progression of cancer. However, the role of PDZRN4 in the progression of BC remains unknown. In the present study, the public database Oncomine was used to detect PDZRN4 expression for primary screening. BC tissues and matched normal tissues were collected for detection of expression and cohort analysis. BC cells were used for invasion and proliferation function tests in vitro and in vivo. The results revealed that both the mRNA and protein levels of PDZRN4 in the BC tissues were markedly reduced compared to normal tissues. The expression of PDZRN4 was significantly correlated with LNM, histological grade and perineural invasion. Prognostic analysis confirmed that PDZRN4 expression is an independent risk factor for overall survival and disease-free survival of patients with BC. The functional experiments demonstrated that knockdown of PDZRN4 significantly improved the invasive and proliferative abilities of BT-20 cells in vitro and in vivo. Furthermore, overexpression of PDZRN4 markedly inhibited the malignant aspects of MDA-MB-231 cells. Therefore, reduced PDZRN4 correlates with the progression of BC and may act as a novel prognostic marker for patients with BC.