ZNF667 Serves as a Putative Oncogene in Human Hepatocellular Carcinoma

Abstract

Background/Aims: Zinc finger protein 667 (ZNF667) is a member of C2H2 zinc finger protein family. For the first time, we aim to analyze the expression pattern of ZNF667 in hepatocellular carcinoma (HCC) tissues; to explore its role in HCC tumorigenesis. Methods: Immuno-histochemistry was carried out to characterize the ZNF667 expression in paraffin-embedded HCC samples. The relationship between ZNF667 expression and the clinical, pathological data of the patients were analyzed. Human normal hepatocyte cells LO2 over expressing ZNF667 (LO2-ZNF667 cells), ZNF667 depleted hepatocellular carcinoma HepG2 cells (HepG2-shZNF667 cells) were set up, their proliferation, migration and invasion abilities were analyzed. Xenograft nude mice were used to analyze the malignancy of HepG2-shZNF667 cells in vivo. Western blot was performed to analyze the expression of Bcl-2 and BAX in LO2-ZNF667 and HepG2-shZNF667 cells. Results: Increased ZNF667 was found via immuno-histochemistry in HCC. Enhanced ZNF667 expression was associated with tumor size, clinical stage and tumor differentiation. LO2-ZNF667 cells displayed increased and HepG2-shZNF667 cells decreased cell proliferation, migration and invasion. Xenograft experiments proved reduced malignancy of HepG2-shZNF667 cells in vivo. LO2-ZNF667 cells displayed increased Bcl-2 and decreased BAX protein expression. HepG2-shZNF667 cells displayed enhanced BAX and inhibited BCL-2 expression. Conclusions: ZNF667 is shown to be a new oncogene in HCC and it may serve as a new therapeutic target for HCC via enhancing BCL-2 and decreasing BAX expression.

Long noncoding RNA ZNF667‐AS1 reduces tumor invasion and metastasis in cervical cancer by counteracting microRNA‐93‐3p‐dependent PEG3 downregulation

“…LncRNAs can modulate gene expression by binding to chromatin regulators and interfering with the functions of RNAs, thereby exercising their effects on cellular responses (Liao et al , ). Zinc finger protein 667 (ZNF667) is an lncRNA capable of regulating numerous cellular processes, such as cell proliferation, migration, and invasion (Cheng et al , ). ZNF667‐antisense RNA 1 (ZNF667‐AS1) is documented as a biomarker and a potential therapeutic target for CC (Zhao et al , ).…”

Aberrant methylation and downregulation of ZNF667-AS1 and ZNF667 promote the malignant progression of laryngeal squamous cell carcinoma

“…Those with low expression of ZNF667 in HNSC tend to had poor survival rate, as indicated by GEPIA (Additional file 2: Figure S1D), with the same trend of ZNF667-AS1. However, Ke Cheng et al reported that ZNF667 was up-regulated in hepatocellular carcinoma and served as a putative oncogene [15]. Given genes are expressed in a cell- and tissue-specific manner, the different roles of ZNF667 in different cancers may be explained by the different basic expression level in normal tissues.…”

“…ZNF667 was suggested to play an important role in oxidative stress [12], and was an anti-apoptotic factor in some conditions [13, 14]. Recently, it was reported that ZNF667 served as a putative oncogene in human hepatocellular carcinoma [15]. The expression of ZNF667 in LSCC is still unknown.…”

Aberrant hypermethylation-mediated downregulation of antisense lncRNA ZNF667-AS1 and its sense gene ZNF667 correlate with progression and prognosis of esophageal squamous cell carcinoma

“…As a head-to-head lncRNA, ZNF667-AS1 and its antisense transcript ZNF667 are both located in 19q13.43. The role of ZNF667-AS1 and ZNF667 has been reported in several types of cancers 11–14,16,24 ; however, the functional role of them in ESCC has not been clarified. ZNF667-AS1 was first reported in a study using microarray analysis to analyze the changed genes in immortalized human mammary epithelial cells (HMEC), and ZNF667-AS1 was found to be expressed in all normal finite lifespan human cells examined to date, and was downregulated or inactivated in immortalized HMEC 11 .…”