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

Abstract

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.

Zinc-Based Biomaterials for Regeneration and Therapy

“…ZFPs represent the largest and most diverse family of DNA binding transcription factors as they can bind to DNA, RNA, and other proteins with high specificity. ZnTs, ZIPs, and ZFPs have demonstrated relevance in important aspects of health ranging from epigenetic changes via DNA methylation [14,15] to development [15][16][17][18], cancer progression/repression [19][20][21][22][23][24][25][26][27], bone remodeling/mineralization, and atherosclerosis.…”

In silico identification of EP400 and TIA1 as critical transcription factors involved in human hepatocellular carcinoma relapse

“…Several forkhead box proteins (14) and zinc finger proteins (ZNFs) (15–21) have also been reported to serve crucial roles in HCC. Recently, a study demonstrated that ZNF687 overexpression promotes HCC recurrence (22); however, the TFs associated with HCC relapse remain unknown (22).…”

ZNF280A promotes lung adenocarcinoma development by regulating the expression of EIF3C

“…For example, Jen et al 20 identified C2H2-type zinc finger protein ZNF322A as a transcriptional inhibitor of c-Myc, thus maintaining lung cancer stem cell-like properties by altering metabolism towards oxidative phosphorylation. Zhang et al 21 found that ZNF687 with C2H2 domain could enhance tumor development and promotes recurrence of hepatocellular carcinoma through transcriptional regulating BMI1, OCT4, and NANOG. On the other hand, although ZNF280A contains two consecutive C2H2-type zinc finger domain transcription factors, there are few studies on its tumor biology.…”