Open AccessZKSCAN 1 gene and its related circular RNA (circ ZKSCAN 1 ) both inhibit hepatocellular carcinoma cell growth, migration, and invasion but through different signaling pathways
Author(s) -
Yao Zhicheng,
Luo Jingyan,
Hu Kunpeng,
Lin Jizong,
Huang He,
Wang Qiangliang,
Zhang Peng,
Xiong Zhiyong,
He Chonghua,
Huang Zejian,
Liu Bo,
Yang Yang
Publication year - 2017
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12045
Subject(s) - gene silencing , circular rna , biology , hepatocellular carcinoma , rna , cell growth , cancer research , cell , gene expression , messenger rna , microbiology and biotechnology , gene , biochemistry
There is increasing evidence that circular RNA (circ RNA ) are involved in cancer development, but the regulation and function of human circ RNA remain largely unknown. In this study, we demonstrated that ZKSCAN 1 , a zinc finger family gene, is expressed in both linear and circular ( circ ZKSCAN 1 ) forms of RNA in human hepatocellular carcinoma ( HCC ) tissues and cell lines. Here, we analyzed a cohort of 102 patients and found that expression of both ZKSCAN 1 mRNA and circ ZKSCAN 1 was significantly lower ( P < 0.05) in the HCC samples compared with that in matched adjacent nontumorous tissues by reverse transcription PCR ( RT ‐ PCR ). The low expression level of ZKSCAN 1 was only associated with tumor size ( P = 0.032), while the cir ZKSCAN 1 levels varied in patients with different tumor numbers ( P < 0.01), cirrhosis ( P = 0.031), vascular invasion ( P = 0.002), or microscopic vascular invasion ( P = 0.002), as well as with the tumor grade ( P < 0.001). Silencing both ZKSCAN 1 mRNA and circ ZKSCAN 1 promoted cell proliferation, migration, and invasion. In contrast, overexpression of both forms of RNA repressed HCC progression in vivo and in vitro . Silencing or overexpression of both forms of RNA did not interfere with each other. RNA ‐seq revealed a very different molecular basis for the observed effects; ZKSCAN 1 mRNA mainly regulated cellular metabolism, while circ ZKSCAN 1 mediated several cancer‐related signaling pathways, suggesting a nonredundant role for ZKSCAN 1 mRNA and circ RNA . In conclusion, our results revealed two post‐translational products ( ZKSCAN 1 mRNA and circ ZKSCAN 1 ) that cooperated closely with one another to inhibit growth, migration, and invasion of HCC . cir ZKSCAN 1 might be a useful marker for the diagnosis of HCC.