MicroRNA Regulation of Cancer Stem Cells and Therapeutic Implications

DeSano, Jeffrey; Xu, Liang

doi:10.1208/s12248-009-9147-7

Cited by 143 publications

(109 citation statements)

References 98 publications

(143 reference statements)

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“…In fact, aberrant expression of miRNAs such as let-7, miR-34a, miR-181a, miRNA-130b in TICs has been found in a variety of tumour types. These aberrantly expressed miRNAs play essential roles in the regulation of TIC properties as either TIC suppressors or promoters [20][21][22][23][24] . Moreover, a series of critical signalling pathways involved in the regulation of TIC properties have been uncovered with the identification of the targets of these miRNAs 19,[25][26][27][28] .…”

mentioning

confidence: 99%

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

Han

Zhao

et al. 2015

Nat Commun

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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 a2d1 subunit marks hepatocellular carcinoma (HCC) TICs. Here we confirm directly that a2d1 is a HCC TIC surface marker, and identify let-7c, miR-200b, miR-222 and miR-424 as suppressors of a2d1 þ 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.

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mentioning

confidence: 99%

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

Han

Zhao

et al. 2015

Nat Commun

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“…miRNAs have been implicated in numerous biological processes, including cell proliferation, metabolism, apoptosis, morphogenesis, developmental timing and stress-response (7)(8)(9). In relation to cancer, miRNAs have been reported to be differentially expressed, acting as oncogenes as well as tumor suppressors (10,11); in addition, numerous miRNA may have the potential for use as diagnostic and prognostic markers in cancer as well as possible therapeutic targets (12)(13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-577 inhibits gastric cancer growth by targeting E2F transcription factor 3

Zhang

Deng

2015

Oncol Lett

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Abstract. The incidence and mortality rates of gastric cancer are one of the highest of all types of cancers. Emerging evidence has demonstrated that altered expression of micro (mi)RNAs may be implicated in the tumorigenesis of numerous types of cancer. Therefore, miRNAs may have potential as important tools in cancer diagnostics and therapeutics. miRNAs regulate the expression of genes involved in mediating cell proliferation and developmental timing, among numerous other processes. Altered expression levels of miRNAs may result in the ability of cells to proliferate aberrantly and migrate. The present study used reverse transcription-quantitative polymerase chain reaction assays to analyze miRNA-577 expression in gastric cancer tissues and cell lines, MTT and cell cycle analysis to examine cell proliferation in vitro, and luciferase assays and western blot to investigate miRNA-577's downstream targets. The results demonstrated that miRNA-577 was significantly downregulated in gastric cancer patient samples and cell lines. In addition, miRNA-577 affected an important regulator of E2F transcription factor 3 expression and that altered miRNA-577 expression resulted in the aberrant proliferation of gastric cancer cells.

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“…Expression of these miRNAs inhibited cell proliferation, promoted apoptosis, and suppressed tumorigenicity both in vitro and in vivo by targeting multiple oncogenes, including Bcl-2, MCL1, CCND1, Wnt3A and Bmi-1. There has been growing evidence illustrated that the pivotal signaling pathways of the "stem cell genes": Notch, Hedgehog, Wnt, HMGA2, Bcl-2 and Bmi-1 were involved in the self-renewal of CSCs 92 . Since the oncogenic activation of Bmi-1, Bcl-2 and Wnt3A were frequently correlated with the downregulation of miR-15/miR-16, it was strongly suggested miR-15/miR-16 played a key role in the regulation of CSCs.…”

Section: Tumor Suppressorsmentioning

confidence: 99%