Mir 145/143: tumor suppressor, oncogenic microenvironmental factor or ...both?

Cioce, Mario; Strano, Sabrina; Muti, Paola; Blandino, Giovanni

doi:10.18632/aging.100965

Cited by 10 publications

(10 citation statements)

References 18 publications

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“…In contrast, our finding in cSCC-an up-regulation of miR-143-5p-supports the recent discussion that the miR-143-145 cluster can act as both a tumor suppressor and, quite unexpectedly, as an oncogenic microenvironmental factor, depending on the tumor entity investigated [46].…”

Section: Discussionsupporting

confidence: 90%

Expression of oncogenic miR-17-92 and tumor suppressive miR-143-145 clusters in basal cell carcinoma and cutaneous squamous cell carcinoma

Sand

Hessam

Amur

et al. 2017

Journal of Dermatological Science

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Section: Discussionsupporting

confidence: 90%

Expression of oncogenic miR-17-92 and tumor suppressive miR-143-145 clusters in basal cell carcinoma and cutaneous squamous cell carcinoma

Sand

Hessam

Amur

et al. 2017

Journal of Dermatological Science

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“…Indeed, both were initially classified as tumorsuppressors based on both expression analysis and functional experiments. [34][35][36] However, several recent publications suggested that their expression can also correlate with tumor progression, metastasis and recurrence in colorectal cancer, esophageal tumors and HBV-related hepatocellular carcinoma, where their functional role was confirmed by in vitro and in vivo experiments. [23][24][25] Additionally, expression of both miRNAs was found to be much higher in mesenchymal cells, including the tumor stroma, than in epithelial cells, suggesting that their assessment in whole tumor biopsies may be misleading.…”

Section: Discussionmentioning

confidence: 98%

MicroRNAs-143 and -145 induce epithelial to mesenchymal transition and modulate the expression of junction proteins

et al. 2017

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Transforming growth factor (TGF)-β is one of the major inducers of epithelial to mesenchymal transition (EMT), a crucial program that has a critical role in promoting carcinoma's metastasis formation. MicroRNAs-143 and -145, which are both TGF-β direct transcriptional targets, are essential for the differentiation of vascular smooth muscle cells (VSMC) during embryogenesis, a TGF-β-dependent process reminiscent of EMT. Their role in adult tissues is however less well defined and even ambiguous, as their expression was correlated both positively and negatively with tumor progression. Here we show that high expression of both miRs-143 and -145 in mouse mammary tumor cells expressing constitutively active STAT3 (S3C) is involved in mediating their disrupted cell-cell junctions. Additionally, miR-143 appears to have a unique role in tumorigenesis by enhancing cell migration in vitro and extravasation in vivo while impairing anchorage-independent growth, which may explain the contradictory reports about its role in tumors. Accordingly, we demonstrate that overexpression of either miRNA in the non-transformed mammary epithelial NMuMG cells leads to upregulation of EMT markers and of several endogenous TGF-β targets, downmodulation of a number of junction proteins and increased motility, correlating with enhanced basal and TGF-β-induced SMAD-mediated transcription. Moreover, pervasive transcriptome perturbation consistent with the described phenotype was observed. In particular, the expression of several transcription factors involved in the mitogenic responses, of MAPK family members and, importantly, of several tight junction proteins and the SMAD co-repressor TGIF was significantly reduced. Our results provide important mechanistic insight into the non-redundant role of miRs-143 and -145 in EMT-related processes in both transformed and non-transformed cells, and suggest that their expression must be finely coordinated to warrant optimal migration/invasion while not interfering with cell growth.

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“…The major therapeutic advantage of miRNAs arises from the fact that a single miRNA can target multiple genes involved in distinct cellular functions. For example, increasing the expression of a tumour-suppressor miRNA (ts-miRNA) like miR-128-3p [11][12][13][14][15][16][17] or miR-145-5p [18][19][20][21][22][23] in GBM can block cell proliferation, self-renewal, invasion, metastasis, angiogenesis and drug resistance by selectively down-regulating the expression of multiple genes, Figure-2. Similarly, repeated systemic treatment with miR-138 blocks multiple key immune-checkpoints proteins in T-cells (CTLA-4, PD-1 and FoxP3), resulting in significant Tcell mediated tumour regression and increased survival in orthotropic brain-tumour model expressing PD-L1 ligand [24].…”

Section: Microrna Therapeutics For Glioblastomamentioning

confidence: 99%

“…The miRNA database (miRBase, version 21) enlists 1881 precursors and 2588 mature human miRNAs [31], of which several of them are identified preferentially as tumour-suppressor miRNA (ts-miRs), as oncomiRs, or as both, depending on the cell type and function of miRNAs in those cells [19,32]. For example, Fareh et al showed forced expression of miR-302/367 cluster in GBM cells resulted in repression of self-renewal properties and in vivo inhibition of tumour development [33].…”

Section: Microrna Therapeutics For Glioblastomamentioning

confidence: 99%

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MicroRNA-Based Drugs for Brain Tumors

et al. 2018

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MicroRNAs (miRNAs) are key regulatory elements encoded by the genome. A single miRNA can downregulate the expression of multiple genes involved in diverse functions. Because cancer is a disease with multiple gene aberrations, developing novel approaches to identify and modulate miRNA pathways may result in a breakthrough for cancer treatment. With a special focus on glioblastoma (GBM), this review provides an up-to-date summary of miRNA biogenesis, the role of miRNA in cancer resistance, and essential tools for modulating miRNA expression, as well as of clinically promising RNAi delivery systems and how they can be adapted for therapy.

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Mir 145/143: tumor suppressor, oncogenic microenvironmental factor or ...both?

Cited by 10 publications

References 18 publications

Expression of oncogenic miR-17-92 and tumor suppressive miR-143-145 clusters in basal cell carcinoma and cutaneous squamous cell carcinoma

Expression of oncogenic miR-17-92 and tumor suppressive miR-143-145 clusters in basal cell carcinoma and cutaneous squamous cell carcinoma

MicroRNAs-143 and -145 induce epithelial to mesenchymal transition and modulate the expression of junction proteins

MicroRNA-Based Drugs for Brain Tumors

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