MicroRNA-23b cluster microRNAs regulate transforming growth factor-beta/bone morphogenetic protein signaling and liver stem cell differentiation by targeting Smads

Rogler, Charles E.; LeVoci, Lauretta; Ader, Tammy; Massimi, Aldo; Tchaikovskaya, Tatyana; Norel, Raquel; Rogler, Leslie E.

doi:10.1002/hep.22982

Cited by 186 publications

(137 citation statements)

References 55 publications

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“…Although a few studies recently demonstrated that miR-23b is involved in invasion and metastasis, the molecular mechanism remains to be elucidated 30,31 . Th e data reported here demonstrated that miR-23b, which is downregulated in human colon cancer samples, could potently repress cancer cell migration, invasion, growth and angiogenesis both in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 99%

Genome-wide functional screening of miR-23b as a pleiotropic modulator suppressing cancer metastasis

et al. 2011

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miRNA globally deregulates human carcinoma. A critical open question is how many miRNAs functionally participate in cancer development, particularly in metastasis. We systematically evaluate the capability of all known human miRNAs to regulate certain metastasis-relevant cell behaviours. To perform the high-throughput screen of miRNAs, which regulate cell migration, we developed a novel self-assembled cell microarray. Here we show that over 20 % of miRNAs have migratory regulation activity in diverse cell types, indicating a general involvement of miRNAs in migratory regulation. MiR-23b, which is downregulated in human colon cancer samples, potently mediates the multiple steps of metastasis, including tumour growth, invasion and angiogenesis in vivo . It regulates a cohort of prometastatic targets, including FZD7 or MAP3k1 . These fi ndings provide new insight into the physiological and potential therapeutic importance of miRNAs as a new class of functional modulators.

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Section: Discussionmentioning

confidence: 99%

Genome-wide functional screening of miR-23b as a pleiotropic modulator suppressing cancer metastasis

et al. 2011

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“…14c and Supplementary Table 3). Interestingly, Bmal1KO cells also expressed lower amounts of the miRNA-23b/-27b/-24-1 cluster, which targets TGFbR2 and Smad proteins 33 (Supplementary Fig. 14d).…”

Section: Loss Of Bmal1 Induces Epidermal Ageingmentioning

confidence: 98%

The circadian molecular clock creates epidermal stem cell heterogeneity

Janich

Pascual

Merlos‐Suárez

et al. 2011

Nature

274

290

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Murine epidermal stem cells undergo alternate cycles of dormancy and activation, fuelling tissue renewal. However, only a subset of stem cells becomes active during each round of morphogenesis, indicating that stem cells coexist in heterogeneous responsive states. Using a circadian-clock reporter-mouse model, here we show that the dormant hair-follicle stem cell niche contains coexisting populations of cells at opposite phases of the clock, which are differentially predisposed to respond to homeostatic cues. The core clock protein Bmal1 modulates the expression of stem cell regulatory genes in an oscillatory manner, to create populations that are either predisposed, or less prone, to activation. Disrupting this clock equilibrium, through deletion of Bmal1 (also known as Arntl) or Per1/2, resulted in a progressive accumulation or depletion of dormant stem cells, respectively. Stem cell arrhythmia also led to premature epidermal ageing, and a reduction in the development of squamous tumours. Our results indicate that the circadian clock fine-tunes the temporal behaviour of epidermal stem cells, and that its perturbation affects homeostasis and the predisposition to tumorigenesis.Epidermal stem cells ensure that skin homeostasis is maintained. Murine epidermal stem cells are located either at the permanent portion of the hair follicle-termed the bulge-and are exclusively responsible for hair cycling [1][2][3][4] ; or at the junction between the epidermis and the hair follicle (isthmus), and feed into the epidermis and sebaceous glands [5][6][7] . In addition, a continuous proliferation of basal interfollicular epidermal cells ensures daily epidermal maintenance 8 .Bulge stem cells undergo bouts of activation followed by periods of dormancy, to establish hair follicle cycling. Robust TGF-b and Bmp signals act as 'activation breaks', rendering bulge cells dormant during the resting phase of the hair cycle (telogen) [9][10][11] . At the onset of the growth phase (anagen), bulge cells respond to Wnt signals by migrating into the lower proliferative hair germ region, where they contribute to follicle growth [12][13][14][15] . Subsequently, at mid-anagen, the bulge undergoes a second round of activation, which replenishes cells lost at the onset of anagen 2,3 . However, the response of bulge stem cells to activating stimuli is a heterogeneous process, as only a subset of them become active during either stage of activation 12,13 . The nature of such niche heterogeneity is currently unknown. Importantly, perturbing the equilibrium between the responsive and non-responsive stem cell states causes tissue malfunction and increases the risk of carcinogenesis [16][17][18][19][20] .Here, we analysed the role of the molecular clock in fine-tuning the function of epidermal stem cells. The mammalian clock machinery anticipates and synchronizes vital functions related to the physiological circadian needs of the organism 21 . The core molecular clock is established by a positive limb, composed of heterodimers of the transcription fa...

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“…While most research efforts to date on miR-27 have been primarily focused on its role in tumorigenesis and embryonic stem cell differentiation (23)(24)(25)(26), many miR-27 targets identified in those studies such as FOXO1, runt-related transcription factor 1 (RUNX1), and SMAD2/3 were known to regulate Treg biology as well (27)(28)(29)(30)(31)(32). We found that, while FOXO1 did not seem to be repressed by miR-27 in T cells, markedly diminished SMAD2/3 and RUNX1 protein levels were detected in T cells that overexpressed miR-27 (Supplemental Figure 6).…”

Section: Mir-27 Targets C-rel a Member Of The Nf-κb Transcription Famentioning

confidence: 99%

Excessive expression of miR-27 impairs Treg-mediated immunological tolerance

Cruz¹,

Hashemifar²,

Wu³

et al. 2017

Journal of Clinical Investigation

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MicroRNA-23b cluster microRNAs regulate transforming growth factor-beta/bone morphogenetic protein signaling and liver stem cell differentiation by targeting Smads

Cited by 186 publications

References 55 publications

Genome-wide functional screening of miR-23b as a pleiotropic modulator suppressing cancer metastasis

Genome-wide functional screening of miR-23b as a pleiotropic modulator suppressing cancer metastasis

The circadian molecular clock creates epidermal stem cell heterogeneity

Excessive expression of miR-27 impairs Treg-mediated immunological tolerance

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