MicroRNA-28-5p Regulates Liver Cancer Stem Cell Expansion via IGF-1 Pathway. (1st December 2019)

• Record Type: Journal Article
• Authors: Xia, Qing; Han, Tao; Yang, Pinghua; Wang, Ruoyu; Li, Hengyu; Zhang, Jin; Zhou, Xinfeng
• Other Names: Sorrenti Valeria Academic Editor.
• Is Part Of: Stem cells international. Volume 2019(2019)
• Publication Date: 2019-12-01
• Subjects: Stem Cells -- Periodicals; Stem Cells -- Therapeutic use -- Periodicals; Stem Cells -- Transplantation -- Periodicals; 616.0277405
• DOI: 10.1155/2019/8734362
• Languages: English
• ISSNs: 1687-966X

Abstract

Abstract : Background . MicroRNAs (miRNAs) play a critical role in the regulation of cancer stem cells (CSCs). However, the role of miRNAs in liver CSCs has not been fully elucidated. Methods . Real-time PCR was used to detect the expression of miR-miR-28-5p in liver cancer stem cells (CSCs). The impact of miR-28-5p on liver CSC expansion was investigated both in vivo and in vitro. The correlation between miR-28-5p expression and sorafenib benefits in HCC was further evaluated in patient-derived xenografts (PDXs). Results . Our data showed that miR-28-5p was downregulated in sorted EpCAM- and CD24-positive liver CSCs. Biofunctional investigations revealed that knockdown miR-28-5p promoted liver CSC self-renewal and tumorigenesis. Consistently, miR-28-5p overexpression inhibited liver CSC's self-renewal and tumorigenesis. Mechanistically, we found that insulin-like growth factor-1 (IGF-1) was a direct target of miR-28-5p in liver CSCs, and the effects of miR-28-5p on liver CSC's self-renewal and tumorigenesis were dependent on IGF-1. The correlation between miR-28-5p and IGF-1 was confirmed in human HCC tissues. Furthermore, the miR-28-5p knockdown HCC cells were more sensitive to sorafenib treatment. Analysis of patient-derived xenografts (PDXs) further demonstrated that the miR-28-5p may predict sorafenib benefits in HCC patients. Conclusion . Our findings revealed the crucial role of the miR-28-5p in liver CSC expansion and sorafenib response, rendering miR-28-5p an optimal therapeutic target for HCC.