PBX3 is targeted by multiple miRNAs and is essential for liver tumour-initiating cells

Haibo Han; Yantao Du; Wei Zhao; Sheng Li; Dongji Chen; Jing Zhang; Jiang Liu; Zhenhe Suo; Xiuwu Bian; Baocai Xing; Zhiqian Zhang

doi:10.1038/ncomms9271

PBX3 is targeted by multiple miRNAs and is essential for liver tumour-initiating cells

Haibo Han
, Yantao Du
, Wei Zhao
, Sheng Li
, Dongji Chen
, Jing Zhang
, Jiang Liu
, Zhenhe Suo
, Xiuwu Bian
, Baocai Xing
, Zhiqian Zhang^*

^*Corresponding author for this work

Peking University
CAS - Beijing Institute of Genomics
University of Oslo
Army Medical University

Research output: Contribution to journal › Article › peer-review

72 Scopus citations

Abstract

Tumour-initiating cells (TIC_s) are advocated to constitute the sustaining force to maintain and renew fully established malignancy; however, the molecular mechanisms responsible for these properties are elusive. We previously demonstrated that voltage-gated calcium channel α2Î 1 subunit marks hepatocellular carcinoma (HCC) TICs. Here we confirm directly that α2Î 1 is a HCC TIC surface marker, and identify let-7_c, miR-200b, miR-222 and miR-424 as suppressors of α2Î 1 + HCC TICs. Interestingly, all the four miRNAs synergistically target PBX3, which is sufficient and necessary for the acquisition and maintenance of TIC properties. Moreover, PBX3 drives an essential transcriptional programme, activating the expression of genes critical for HCC TIC stemness including CACNA2D1, EpCAM, SOX2 and NOTCH3. In addition, the expression of CACNA2D1 and PBX3 mRNA is predictive of poor prognosis for HCC patients. Collectively, our study identifies an essential signalling pathway that controls the switch of HCC TIC phenotypes.

Original language	English
Article number	8271
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms9271
State	Published - 30 Sep 2015
Externally published	Yes

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@article{aa6dd03517b142a582868df7402df526,

title = "PBX3 is targeted by multiple miRNAs and is essential for liver tumour-initiating cells",

abstract = "Tumour-initiating cells (TICs) are advocated to constitute the sustaining force to maintain and renew fully established malignancy; however, the molecular mechanisms responsible for these properties are elusive. We previously demonstrated that voltage-gated calcium channel α2{\^I} 1 subunit marks hepatocellular carcinoma (HCC) TICs. Here we confirm directly that α2{\^I} 1 is a HCC TIC surface marker, and identify let-7c, miR-200b, miR-222 and miR-424 as suppressors of α2{\^I} 1 + HCC TICs. Interestingly, all the four miRNAs synergistically target PBX3, which is sufficient and necessary for the acquisition and maintenance of TIC properties. Moreover, PBX3 drives an essential transcriptional programme, activating the expression of genes critical for HCC TIC stemness including CACNA2D1, EpCAM, SOX2 and NOTCH3. In addition, the expression of CACNA2D1 and PBX3 mRNA is predictive of poor prognosis for HCC patients. Collectively, our study identifies an essential signalling pathway that controls the switch of HCC TIC phenotypes.",

author = "Haibo Han and Yantao Du and Wei Zhao and Sheng Li and Dongji Chen and Jing Zhang and Jiang Liu and Zhenhe Suo and Xiuwu Bian and Baocai Xing and Zhiqian Zhang",

note = "Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",

year = "2015",

month = sep,

day = "30",

doi = "10.1038/ncomms9271",

language = "英语",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

}

TY - JOUR

T1 - PBX3 is targeted by multiple miRNAs and is essential for liver tumour-initiating cells

AU - Han, Haibo

AU - Du, Yantao

AU - Zhao, Wei

AU - Li, Sheng

AU - Chen, Dongji

AU - Zhang, Jing

AU - Liu, Jiang

AU - Suo, Zhenhe

AU - Bian, Xiuwu

AU - Xing, Baocai

AU - Zhang, Zhiqian

PY - 2015/9/30

Y1 - 2015/9/30

N2 - Tumour-initiating cells (TICs) are advocated to constitute the sustaining force to maintain and renew fully established malignancy; however, the molecular mechanisms responsible for these properties are elusive. We previously demonstrated that voltage-gated calcium channel α2Î 1 subunit marks hepatocellular carcinoma (HCC) TICs. Here we confirm directly that α2Î 1 is a HCC TIC surface marker, and identify let-7c, miR-200b, miR-222 and miR-424 as suppressors of α2Î 1 + HCC TICs. Interestingly, all the four miRNAs synergistically target PBX3, which is sufficient and necessary for the acquisition and maintenance of TIC properties. Moreover, PBX3 drives an essential transcriptional programme, activating the expression of genes critical for HCC TIC stemness including CACNA2D1, EpCAM, SOX2 and NOTCH3. In addition, the expression of CACNA2D1 and PBX3 mRNA is predictive of poor prognosis for HCC patients. Collectively, our study identifies an essential signalling pathway that controls the switch of HCC TIC phenotypes.

AB - Tumour-initiating cells (TICs) are advocated to constitute the sustaining force to maintain and renew fully established malignancy; however, the molecular mechanisms responsible for these properties are elusive. We previously demonstrated that voltage-gated calcium channel α2Î 1 subunit marks hepatocellular carcinoma (HCC) TICs. Here we confirm directly that α2Î 1 is a HCC TIC surface marker, and identify let-7c, miR-200b, miR-222 and miR-424 as suppressors of α2Î 1 + HCC TICs. Interestingly, all the four miRNAs synergistically target PBX3, which is sufficient and necessary for the acquisition and maintenance of TIC properties. Moreover, PBX3 drives an essential transcriptional programme, activating the expression of genes critical for HCC TIC stemness including CACNA2D1, EpCAM, SOX2 and NOTCH3. In addition, the expression of CACNA2D1 and PBX3 mRNA is predictive of poor prognosis for HCC patients. Collectively, our study identifies an essential signalling pathway that controls the switch of HCC TIC phenotypes.

UR - https://www.scopus.com/pages/publications/84942849452

U2 - 10.1038/ncomms9271

DO - 10.1038/ncomms9271

M3 - 文章

C2 - 26420065

AN - SCOPUS:84942849452

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 8271

ER -

PBX3 is targeted by multiple miRNAs and is essential for liver tumour-initiating cells

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