Oncotarget

Research Papers:

MicroRNA31 suppresses the selfrenewal capability of α2δ1+ liver tumorinitiating cells by targeting ISL1

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Oncotarget. 2017; 8:87647-87657. https://doi.org/10.18632/oncotarget.21140

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Yuan Zhang1, Wei Zhao1, Haibo Han1, Sheng Li1, Dongji Chen1 and Zhiqian Zhang1

1Department of Cell Biology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China

Correspondence to:

Zhiqian Zhang, email: [email protected]

Keywords: MicroRNA, hepatocellular carcinoma, tumor-initiating cell, miR-31, ISL1

Received: March 06, 2017     Accepted: August 26, 2017     Published: September 21, 2017

ABSTRACT

Accumulating evidence demonstrates that miRNAs, a class of small non-coding RNAs, are involved in the regulation of tumor-initiating cells (TICs) which are considered to be the origin of cancer development according to the cancer stem cell hypothesis. We have previously identified that miR-31 may play suppressive roles in α2δ1+ hepatocellular carcinoma (HCC) TICs. Here, we confirm that the expression of miR-31 is significantly downregulated in α2δ1+ HCC TICs. Overexpression of miR-31 in α2δ1+ HCC TICs results in significant suppression of the self-renewal and tumorigenicity abilities of these cells. Conversely, knockdown the expression of miR-31 in PLC/PRF/5 cells is able to reprogram them into TICs with stem cell-like properties. Furthermore, the expression of ISL LIM Homeobox 1(ISL1), a transcription factor involved in recognition of undifferentiated cardiac progenitors, is negatively regulated by miR-31, and the luciferase reporters’ activities with the 3’-UTRs of ISL1 are inhibited significantly by miR-31. Collectively, our results suggest that miR-31 can negatively regulate the self-renewal ability of α2δ1+ liver TICs via silencing ISL1.