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
N1 - Publisher Copyright:
© 2015 Macmillan Publishers Limited.
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 -