Abstract

Zinc finger protein307 (ZNF307) is a new Krüppel-associated box zinc-finger protein gene and a member of the zinc-finger family of transcriptional factors. Notably, the role of ZNF307 and its underlying mechanisms involved in hepatocarcinogenesis are poorly investigated. In the present study, we found that the expression of ZNF307 was significantly downregulated in hepatocellular carcinoma (HCC) tissues, compared with that in adjacent non-tumor tissues. Invitro studies further demonstrated that ectopic expression of ZNF307 in HCC cell lines Bel7402 and HCCLM3 significantly reduced cell proliferation, migration and invasive ability. Concordantly, knockdown of ZNF307 increased cell proliferation, migration and invasive ability of HCC cell lines MHCC97L and QGY7701. Invivo functional studies showed that upregulation of ZNF307 expression in Bel7402 cells led to a suppression of tumorigenicity in mice, while knockdown of ZNF307 in MHCC97L cells resulted in reverse. effects. Importantly, flow cytometric analysis showed that ZNF307 overexpression increased the incidence of apoptosis, while ZNF307 knockdown decreased the incidence of apoptosis. Consistently, key regulators in apoptosis, such as caspase-3, BAX and BCL-2 were also regulated by ZNF307. Therefore, our results indicate that ZNF307 may serve as a tumor suppressor and inhibits cell proliferation of HCC via inducing apoptosis.

Highlights

  • Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death among males worldwide as well as inKey words: hepatocellular carcinoma, zinc finger protein 307 less developed countries

  • Zinc finger protein 307 (ZNF307) mRNA levels were measured in 33-paired HCC and adjacent non-tumor tissues by real-time PCR

  • The result revealed that ZNF307 mRNA levels were significantly downregulated in the HCC tissues (P

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Summary

Introduction

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death among males worldwide as well as in. The functions of zinc-finger proteins are of great diversity, including DNA recognition, RNA packaging, transcriptional activation and regulation of apoptosis [6]. Due to their multiple functions, several zinc-finger proteins have been identified as tumor-suppressors or oncogenes in the development of tumors. Zinc-finger protein X-linked (ZFX) has been identified as an oncogene in colorectal cancer and is associated with poor prognosis [9]. The role of most zinc-finger family members in tumor development remains ambiguous including HCC [14].

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