Musashi 2 contributes to the stemness and chemoresistance of liver cancer stem cells via LIN28A activation

Fang, Tian; Lv, Hongwei; Wu, Fengyuan; Wang, Changzheng; Li, Ting; Lv, Guishuai; Tang, Liang; Guo, Linna; Tang, Shanhua; Cao, Dan; Wu, Mengchao; Yang, Wen; Wang, Hongyang

doi:10.1016/j.canlet.2016.10.007

Cited by 50 publications

(55 citation statements)

References 32 publications

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“…Overall, these and other studies have identified a large number of targets of Musashi-dependent expression, which besides those mentioned above include Hoxa9, Myc, Ikzf2 (53), NF-YA, a regulator of the proteasome (59), and Jagged1 (54). Musashi proteins have also recently been reported influence expression of lin28A, joining other studies connecting these proteins to control of cancer-associated micro-RNAs (miRs) (60,61). Factors of general interest for many cancers are summarized in Table 2.…”

Section: Demonstration Of Driver Roles For Musashi Expression In Oncomentioning

confidence: 84%

“…In contrast, overexpression of either Xenopus or mouse MSI1 in the context of GLD2-depleted mouse cells led to translational inhibition. Connecting Musashi proteins to control of miRS, discrete LIN28-binding motif has been identified in the C-terminus of MSI1 (9): while this motif is absent in MSI2, recent studies have nevertheless shown biological activity of MSI2 in regulating Lin28A (23,61). Additionally, both MSI1 and MSI2 have been described to regulate alternative splicing in mouse retinal photoreceptor and neural stem cells, with mechanisms still to be exactly defined (54,71).…”

Section: Mechanisms Of Post-transcriptional Regulation By Musashi Promentioning

confidence: 99%

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Musashi RNA-Binding Proteins as Cancer Drivers and Novel Therapeutic Targets

Kudinov

Karanicolas

Golemis

et al. 2017

Clinical Cancer Research

213

240

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Aberrant gene expression that drives human cancer can arise from epigenetic dysregulation. While much attention has focused on altered activity of transcription factors and chromatin-modulating proteins, proteins that act post-transcriptionally can potently affect expression of oncogenic signaling proteins. The RNA-binding proteins (RBPs) Musashi-1 (MSI1) and Musashi-2 (MSI2) are emerging as regulators of multiple critical biological processes relevant to cancer initiation, progression, and drug resistance. Following identification of Musashi as regulators of progenitor cell identity in Drosophila, the human Musashi proteins were initially linked to control of maintenance of hematopoietic stem cells, then stem cell compartments for additional cell types. More recently, the Musashi proteins were found to be overexpressed and prognostic of outcome in numerous cancer types, including colorectal, lung, and pancreatic cancers, glioblastoma, and several leukemias. MSI1 and MSI2 bind and regulate the mRNA stability and translation of proteins operating in essential oncogenic signaling pathways, including NUMB/Notch, PTEN/mTOR, TGF-β/SMAD3, MYC, cMET, and others. Based on these activities, MSI proteins maintain cancer stem cell populations and regulate cancer invasion, metastasis and development of more aggressive cancer phenotypes, including drug resistance. While RBPs are viewed as difficult therapeutic targets, initial efforts to develop MSI-specific inhibitors are promising and RNA interference-based approaches to inhibiting these proteins have had promising outcomes in preclinical studies. In the interim, understanding the function of these translational regulators may yield insight into the relationship between mRNA expression and protein expression in tumors, guiding tumor profiling analysis. This review provides a current overview of Musashi as a cancer driver and novel therapeutic target.

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Section: Demonstration Of Driver Roles For Musashi Expression In Oncomentioning

confidence: 84%

Section: Mechanisms Of Post-transcriptional Regulation By Musashi Promentioning

confidence: 99%

Musashi RNA-Binding Proteins as Cancer Drivers and Novel Therapeutic Targets

Kudinov

Karanicolas

Golemis

et al. 2017

Clinical Cancer Research

213

240

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“…Despite the challenges for in vivo administration, we reduced the disease burden in an aggressive MLL-AF9 leukemia model and decreased MYC levels without overt toxicity. Interestingly, it has previously been shown that MSI2 can contribute to chemotherapeutic resistance in different cancer models 42,55,56 . Future studies could examine if combination therapies could provide additional clinical benefit.…”

Section: Discussionmentioning

confidence: 99%

Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia

Minuesa

Albanese

Chow

et al. 2018

Preprint

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“…Although Lin28a and Lin28b share a high degree of homology in function and structure, Lin28a is primarily located in the cytoplasm of cells, whereas Lin28b predominantly localizes to the nucleolus. In mammals, Lin28a is highly expressed during embryogenesis and cooperates with pluripotent transcripition factors, specifically OCT‐4, SOX2, and NANOG, to reprogram human somatic cells into induced pluripotent stem cells …”

Section: Discussionmentioning

confidence: 99%

“…In mammals, Lin28a is highly expressed during embryogenesis and cooperates with pluripotent transcripition factors, specifically OCT-4, SOX2, and NANOG, to reprogram human somatic cells into induced pluripotent stem cells. 6,10,11,[21][22][23] Lin28a has been cited as a marker of stemness, as indicated by an ability for long-term self-renewal and a capacity to differentiate into diverse mature tissue. 10,[24][25][26] In this study, we have examined the effect of the Lin28a gene on in vitro osteoblastic differentiation and cellular senescence of cultured hPDCs.…”

Section: Reactive Oxygen Species Lactate and Adenosine Triphosphamentioning

confidence: 99%

Lin28a enhances in vitro osteoblastic differentiation of human periosteum‐derived cells

Park

Kang

et al. 2017

Cell Biochemistry & Function

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Despite a capacity for proliferation and an ability to differentiate into multiple cell types, in long-term culture and with ageing, stem cells show a reduction in growth, display a decrease in differentiation potential, and enter senescence without evidence of transformation. The Lin28a gene encodes an RNA-binding protein that plays a role in regulating stem cell activity, including self-renewal and differentiation propensity. However, the effect of the Lin28a gene on cultured human osteoprecursor cells is poorly understood. In the present study, alkaline phosphatase activity, alizarin red-positive mineralization, and calcium content, positive indicators of osteogenic differentiation, were significantly higher in cultured human periosteum-derived cells (hPDCs) with Lin28a overexpression compared with cells without Lin28a overexpression. Lin28a overexpression by hPDCs also increased mitochondrial activity, which is essential for cellular proliferation, as suggested by a reduced presence of reactive oxygen species and significantly enhanced lactate levels and ATP production. Our results suggest that, in hPDCs, the Lin28a gene enhances osteoblastic differentiation and increases mitochondrial activity. Although Lin28a is known as a marker of undifferentiated human embryogenic stem cell, there is limited evidence regarding the influence of Lin28a on osteoblastic differentiation of cultured osteoprecursor cells. This study was to examine the impact of Lin28a on osteogenic phenotypes of human periosteum-derived cells. Their phenotypes can be similar to those of mesenchymal stem cells. Our results suggest that the Lin28a gene enhances the osteoblastic differentiation of human periosteum-derived cells. In addition, the Lin28a gene increases mitochondrial activity in human periosteum-derived cells.

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Musashi 2 contributes to the stemness and chemoresistance of liver cancer stem cells via LIN28A activation

Cited by 50 publications

References 32 publications

Musashi RNA-Binding Proteins as Cancer Drivers and Novel Therapeutic Targets

Musashi RNA-Binding Proteins as Cancer Drivers and Novel Therapeutic Targets

Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia

Lin28a enhances in vitro osteoblastic differentiation of human periosteum‐derived cells

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