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Molecular Cancer
Published in: Molecular Cancer 1/2019

Open Access 01-12-2019 | Hepatocellular Carcinoma | Research

KIAA1429 contributes to liver cancer progression through N6-methyladenosine-dependent post-transcriptional modification of GATA3

Authors: Tian Lan, Hui Li, Delin Zhang, Lin Xu, Hailing Liu, Xiangyong Hao, Xiaokai Yan, Haotian Liao, Xiangzheng Chen, Kunlin Xie, Jiaxin Li, Mingheng Liao, Jiwei Huang, Kefei Yuan, Yong Zeng, Hong Wu

Published in: Molecular Cancer | Issue 1/2019

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Abstract

Background

N6-methyladenosine (m6A) modification, the most abundant internal methylation of eukaryotic RNA transcripts, is critically implicated in RNA processing. As the largest known component in the m6A methyltransferase complex, KIAA1429 plays a vital role in m6A methylation. However, its function and mechanism in hepatocellular carcinoma (HCC) remain poorly defined.

Methods

Quantitative PCR, western blot and immunohistochemistry were used to measure the expression of KIAA1429 in HCC. The effects of KIAA1429 on the malignant phenotypes of hepatoma cells were examined in vitro and in vivo. MeRIP-seq, RIP-seq and RNA-seq were performed to identify the target genes of KIAA1429.

Results

KIAA1429 was considerably upregulated in HCC tissues. High expression of KIAA1429 was associated with poor prognosis among HCC patients. Silencing KIAA1429 suppressed cell proliferation and metastasis in vitro and in vivo. GATA3 was identified as the direct downstream target of KIAA1429-mediated m6A modification. KIAA1429 induced m6A methylation on the 3′ UTR of GATA3 pre-mRNA, leading to the separation of the RNA-binding protein HuR and the degradation of GATA3 pre-mRNA. Strikingly, a long noncoding RNA (lncRNA) GATA3-AS, transcribed from the antisense strand of the GATA3 gene, functioned as a cis-acting element for the preferential interaction of KIAA1429 with GATA3 pre-mRNA. Accordingly, we found that the tumor growth and metastasis driven by KIAA1429 or GATA3-AS were mediated by GATA3.

Conclusion

Our study proposed a complex KIAA1429-GATA3 regulatory model based on m6A modification and provided insights into the epi-transcriptomic dysregulation in hepatocarcinogenesis and metastasis.
Appendix
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Metadata
Title
KIAA1429 contributes to liver cancer progression through N6-methyladenosine-dependent post-transcriptional modification of GATA3
Authors
Tian Lan
Hui Li
Delin Zhang
Lin Xu
Hailing Liu
Xiangyong Hao
Xiaokai Yan
Haotian Liao
Xiangzheng Chen
Kunlin Xie
Jiaxin Li
Mingheng Liao
Jiwei Huang
Kefei Yuan
Yong Zeng
Hong Wu
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2019
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-019-1106-z

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