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Long noncoding RNA FTX inhibits hepatocellular carcinoma proliferation and metastasis by binding MCM2 and miR-374a

Oncogene volume 35, pages 5422–5434 (2016)Cite this article

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Abstract

It has long been known that males are more susceptible than females to hepatocellular carcinoma (HCC), but the reason remains elusive. In this study, we investigated the expression and function of the long noncoding RNA FTX (lnc-FTX), an X-inactive-specific transcript (XIST) regulator transcribed from the X chromosome inactivation center, in both HCC and HCC gender disparity. lnc-FTX is expressed at higher levels in female livers than in male livers and is significantly downregulated in HCC tissues compared with normal liver tissues. Patients with higher lnc-FTX expression exhibited longer survival, suggesting that lnc-FTX is a useful prognostic factor for HCC patients. lnc-FTX inhibits HCC cell growth and metastasis both in vitro and in vivo. Mechanistically, lnc-FTX represses Wnt/β-catenin signaling activity by competitively sponging miR-374a and inhibits HCC cell epithelial–mesenchymal transition and invasion. In addition, lnc-FTX binds to the DNA replication licensing factor MCM2, thereby impeding DNA replication and inhibiting proliferation in HCC cells. In conclusion, these findings suggest that lnc-FTX may act as a tumor suppressor in HCC through physically binding miR-374a and MCM2. It may also be one of the reasons for HCC gender disparity and may potentially contribute to HCC treatment.

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Abbreviations

AFP:

α-fetoprotein

EdU:

5-ethynyl-2′-deoxyuridine

EMT:

epithelial–mesenchymal transition

HCC:

hepatocellular carcinoma

lnc-FTX:

long noncoding RNA FTX

lncRNA:

long non-coding RNA

MCM2:

minichromosome maintenance complex component 2

XCI:

X chromosome inactivation

XIST:

X-inactive-specific transcript

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Acknowledgements

We thank Dr Le Qu and Mr Zhi-peng Xu from Department of Urology, Shanghai Changzheng Hospital and Dr Sheng-Xian Yuan and Dr Qi-Fei Tao from the Third Department of Hepatic Surgery, Eastern Hepatobiliary Hospital for technical assistance. This work was supported by grants from the State Key Program of National Natural Science Foundation of China (grant nos 81330037), the National Key Basic Research Program of China (973 Program) (grant nos 2015CB554004), the National Natural Science Foundation of China (grant nos 31201025, 81301831, 81301692, 81472691 and 81402269, and the National Natural Science Foundation of Shanghai (13ZR1448300).

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Authors and Affiliations

  1. Department of Medical Genetics, Second Military Medical University, Shanghai, China

    F Liu, J-H Yuan, J-F Huang, F Yang, T-T Wang, J-Z Ma, L Zhang, C-C Zhou, F Wang & S-H Sun

  2. The Third Department of Hepatic Surgery, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, China

    J Yu & W-P Zhou

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  1. F Liu
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Correspondence to S-H Sun.

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Liu, F., Yuan, JH., Huang, JF. et al. Long noncoding RNA FTX inhibits hepatocellular carcinoma proliferation and metastasis by binding MCM2 and miR-374a. Oncogene 35, 5422–5434 (2016). https://doi.org/10.1038/onc.2016.80

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