miRNA let-7e targeting MMP9 is involved in adipose-derived stem cell differentiation toward epithelia

Ventayol, Marina; Viñas, Jose Luis; Solà, Anna; Jung, Michaela; Brüne, Bernhard; Pi, Felip; Mastora, Chrysoula; Hotter, Georgina

doi:10.1038/cddis.2014.2

Cited by 37 publications

(36 citation statements)

References 46 publications

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“…Peptides (P17 and P144) targeting EMT also inhibit the expression of CD44 and SOX2 [41]. Keratin 18 is considered as a differentiation and epithelial marker, indicating differentiation and mesenchymal-epithelial transition (MET) of breast cancer cells [42, 43], while Vimentin functions as a dedifferentiation and mesenchymal marker in breast cancer cells [44, 45]. In the present study, we found that flubendazole treated MDA-MB-231 cells expressed high level of Keratin 18 and low level of β-catenin, N-cadherin and Vimentin (Fig.…”

Section: Discussionmentioning

confidence: 99%

Flubendazole, FDA-approved anthelmintic, targets breast cancer stem-like cells

et al. 2015

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Cancer stem-like cell (CS-like cell) is considered to be responsible for recurrence and drug resistance events in breast cancer, which makes it a potential target for novel cancer therapeutic strategy. The FDA approved flubendazole, has been widely used in the treatment of intestinal parasites. Here, we demonstrated a novel effect of flubendazole on breast CS-like cells. Flubendazole inhibited breast cancer cells proliferation in dose- and time-dependent manner and delayed tumor growth in xenograft models by intraperitoneal injection. Importantly, flubendazole reduced CD44high/CD24low subpopulation and suppressed the formation of mammosphere and the expression of self-renewal related genes including c-myc, oct4, sox2, nanog and cyclinD1. Moreover, we found that flubendazole induced cell differentiation and inhibited cell migration. Consistently, flubendazole reduced mesenchymal markers (β-catenin, N-cadherin and Vimentin) expression and induced epithelial and differentiation marker (Keratin 18) expression in breast cancer cells. Mechanism study revealed that flubendazole arrested cell cycle at G2/M phase and induced monopolar spindle formation through inhibiting tubulin polymerization. Furthermore, flubendazole enhanced cytotoxic activity of conventional therapeutic drugs fluorouracil and doxorubicin against breast cancer cells. In conclusion, our findings uncovered a remarkable effect of flubendazole on suppressing breast CS-like cells, indicating a novel utilization of flubendazole in breast cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Flubendazole, FDA-approved anthelmintic, targets breast cancer stem-like cells

et al. 2015

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“…Further studies are needed to find a link between miR-98, E2F5 and the TGFB regulation of myogenesis. let-7 miRNAs, which influence the timing of Caenorhabditis elegans development, have been implicated in regulating cell proliferation and differentiation of numerous cell and tissue types, such as neuronal, cardiac, adipogenic and others ( [17][18][19][20][21], reviewed in [3]) in mammals. In a few cases, a let-7 miRNA acted as a negative regulator of differentiation, via an unknown mechanism [22].…”

Section: E2f5 Directly Down-regulates the Differentiation Inhibitors mentioning

confidence: 99%

miR-98 delays skeletal muscle differentiation by down-regulating E2F5

Kropp

Degerny

Morozova

et al. 2015

Biochemical Journal

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A genome-wide screen had previously shown that knocking down miR-98 and let-7g, two miRNAs of the let-7 family, leads to a dramatic increase in terminal myogenic differentiation. In the present paper, we report that a transcriptomic analysis of human myoblasts, where miR-98 was knocked down, revealed that approximately 240 genes were sensitive to miR-98 depletion. Among these potential targets of miR-98, we identified the transcriptional repressor E2F5 and showed that it is a direct target of miR-98. Knocking down simultaneously E2F5 and miR-98 almost fully restored normal differentiation, indicating that E2F5 is involved in the regulation of skeletal muscle differentiation. We subsequently show that E2F5 can bind to the promoters of two inhibitors of terminal muscle differentiation, ID1 (inhibitor of DNA binding 1) and HMOX1 (heme oxygenase 1), which decreases their expression in skeletal myoblasts. We conclude that miR-98 regulates muscle differentiation by altering the expression of the transcription factor E2F5 and, in turn, of multiple E2F5 targets.

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“…The immunofluorescence confirmed that rEPCs could be differentiated from rADSCs. According to the data from the literature and this study, isolating ADSCs from patients for clinical applications has great potential. The morphology of the PCL scaffolds observed by SEM showed that their fiber diameters were in the submicron range, which fulfilled the necessity of mimicking the ECM and contributed to the cell attachment and proliferation for the regeneration of the natural tissues.…”

Section: Discussionmentioning

confidence: 92%