Overexpression of zinc finger protein 687 enhances tumorigenic capability and promotes recurrence of hepatocellular carcinoma

Zinc finger protein 687 (ZNF687), identified as a C2H2 zinc finger protein, has been found to be mutated and upregulated in giant cell tumor of bone and acute myeloid leukemia, suggesting an oncogenic role for ZNF687 in cancer. However, the clinical significance and precise role of ZNF687 in cancer progression are largely unknown. Herein, we report that ZNF687 was markedly upregulated in hepatocellular carcinoma (HCC) cell lines and HCC tissues, and was significantly correlated with relapse-free survival in HCC. ZNF687 overexpression greatly enhanced HCC cell capability for tumorsphere formation, invasion and chemoresistance in vitro, whereas inhibiting ZNF687 reduced these capabilities and inhibited HCC cell tumorigenic capability in vivo. Importantly, extreme limiting dilution analysis revealed that even 1 × 102 ZNF687-transduced cells could form tumors in vivo, indicating that ZNF687 contributes to HCC recurrence. Moreover, we demonstrate that ZNF687 transcriptionally upregulated the expression of the pluripotency-associated factors BMI1, OCT4 and NANOG by directly targeting their promoters. Therefore, our results suggest that ZNF687 has a promoter role in regulating HCC progression, which provides a potential therapeutic target for HCC in humans.