Knockdown of ZFX suppresses renal carcinoma cell growth and induces apoptosis

The ZFX (zinc finger protein, X-linked) gene located on the human X chromosome controls the self-renewal of embryonic and hematopoietic stem cells as a transcriptional regulator. Recently, studies have affirmed that ZFX is associated with several human cancers, including lymphoma, laryngeal squamous cell carcinoma, prostate cancer, and liver cancer, which suggests ZFX as a potential therapeutic target in cancer. However, the functional role of ZFX in human renal cancer remains unclear. Herein, we detected the expression of ZFX in 42 patients with renal cancer and found the expression of ZFX was specifically upregulated in cancer tissues at the mRNA and protein levels. Moreover, we employed lentivirus-mediated short hairpin RNA (shRNA) to knock down ZFX expression in two human renal cell carcinoma cell lines, 786-0 and ACHN. Functional analysis indicated that ZFX silencing significantly inhibited renal cell carcinoma cell proliferation and cell cycle progression, probably because of suppression of CDK4 and cyclin D1 and induced apoptosis via activation of Bax, Caspase 3, and PUMA in a p53-dependent manner. Our findings suggest that knockdown of ZFX by shRNA may be a potential therapeutic approach for the treatment of renal cancer.