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Carcinogenesis. 2019 May 14;40(3):474-486. doi: 10.1093/carcin/bgy146.

Downregulation of ZC3H14 driven by chromosome 14q31 deletion promotes hepatocellular carcinoma progression by activating integrin signaling.

Zhang C1,2,3, Cao P2,3, Yang A2,3, Xia X2,3, Li Y2,3, Shi M4, Yang Y5, Wei X6, Yang C1, Zhou G2,3,4.

Author information

1
Affiliated Tumor Hospital of Guangxi Medical University, Nanning, P. R. China.
2
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, P. R. China.
3
National Center for Protein Sciences at Beijing, Beijing, P. R. China.
4
Guangxi Medical University, Nanning, P. R. China.
5
Department of Radiation and Oncology, Navy General Hospital, Beijing, P. R. China.
6
Department of Hepatobiliary Surgery, Aerospace Center Hospital, Beijing, P. R. China.

Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Genomic copy number deletion at chromosome 14q31.1-32.13 was frequently observed in HCC; however, the relevant functional target(s) at that locus is not well determined. Here, we performed integrative genomic analyses and identified zinc finger CCCH-type containing 14 (ZC3H14) as a promising candidate at 14q31.1-32.13. We observed frequent copy number deletion (17.1%) and downregulation of ZC3H14 in primary HCC tissues. Downregulation of ZC3H14 was significantly associated with poor outcomes of patients with HCC. Overexpression of ZC3H14 in HCC cell lines significantly suppressed HCC cells growth in vitro and metastasis in vivo. In contrast, RNA interference silencing of ZC3H14 inhibited its tumor-suppressive function. Mechanismly, through combing bioinformatics analyses and experimental investigation, we demonstrated that loss of ZC3H14 promotes HCC progression through enhancing integrin pathway. This study suggests that ZC3H14 functions as a novel tumor suppressor and is a candidate prognostic biomarker for HCC patients.

PMID:
30371740
DOI:
10.1093/carcin/bgy146

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