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Long noncoding RNA ZNFX1-AS1 suppresses growth of hepatocellular carcinoma cells by regulating the methylation of miR-9

Authors Wang T, Ma S, Qi X, Tang X, Cui D, Wang Z, Chi J, Li P, Zhai B

Received 29 December 2015

Accepted for publication 29 March 2016

Published 12 August 2016 Volume 2016:9 Pages 5005—5014

DOI https://doi.org/10.2147/OTT.S103329

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Lucy Goodman

Peer reviewer comments 2

Editor who approved publication: Dr William Cho


Tao Wang, Sicong Ma, Xingxing Qi, Xiaoyin Tang, Dan Cui, Zhi Wang, Jiachang Chi, Ping Li, Bo Zhai

Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China

Abstract: Many long noncoding RNAs have been reported to play pivotal roles in cancer biology. Among them, the long noncoding RNA ZNFX1-AS1 has been confirmed to function in breast cancer progression, but the role of ZNFX1-AS1 in hepatocellular carcinoma (HCC) growth and the related molecular mechanisms still remains unknown. In the present study, we first identified the expression of ZNFX1-AS1 in HCC patients’ specimens and HCC cell lines through quantitative reverse transcription polymerase chain reaction. Next, the effects of ZNFX1-AS1 on HCC cell growth and apoptosis were analyzed. MTT assay was used to measure the cell numbers, and fluorescence-activated cell sorting analysis was performed to evaluate cell apoptosis. Finally, the relationship between ZNFX1-AS1 and miR-9 in HCC was studied. Our results suggest that ZNFX1-AS1 was markedly downregulated in HCC samples and cell lines. Overexpression of ZNFX1-AS1 inhibited the cell proliferation and colony formation in HCC cell lines and also induced HCC cell apoptosis. Additionally, miR-9 was lowly expressed in HCC tissues and positively correlated with ZNFX1-AS1 expression. Meanwhile, significant upregulation of miR-9 and downregulation of the methylation of miR-9 promoter CpG island were observed when ZNFX1-AS1 was overexpressed. In summary, our results indicate that ZNFX1-AS1 plays a vital role in HCC progression via regulating the methylation of miR-9 and may be a potential tumor suppressor.

Keywords:
ZNFX1-AS1, hepatocellular carcinoma, miR-9, methylation

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