Transcription Factor/microRNA Axis Blocks Melanoma Invasion Program by miR-211 Targeting NUAK1

Bell, Rachel E.; Khaled, Mehdi; Netanely, Dvir; Schubert, Steffen; Golan, Tamar; Buxbaum, Amir; Janas, Maja M.; Postolsky, Benny; Goldberg, Michael S.; Shamir, Ron

doi:10.1038/jid.2013.340

Cited by 109 publications

(140 citation statements)

References 66 publications

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“…Recently, abundant studies have already reported the importance of miRNAs in an increasing number of cancers [5,6]. In melanoma, some miRNAs have been found abnormally expressed, such as miR-153-3p [7], miR-211 [8], miR-196a [9], miR-30b, and miR-30d [10]. They have been revealed as oncogenes or tumor suppressor genes in melanoma.…”

Section: Introductionmentioning

confidence: 99%

“…They have been revealed as oncogenes or tumor suppressor genes in melanoma. For instance, ectopic expression of miR-211 in melanoma cell lines resulted in significant inhibition of growth and invasion compared to parental cells [8]. Contrary to miR-211, miR-30b and miR-30d were reported to have functions as potential tumor promoters, as evidenced by simultaneously promoting cellular invasion and immunosuppression in melanoma cells [10].…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-29a Inhibits Growth, Migration and Invasion of Melanoma A375 Cells in Vitro by Directly Targeting BMI1

Xiong

Liu

Qiu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Melanoma is one of the most aggressive malignant tumors, with increasing incidence, poor prognosis, and lack of any effective targeted therapies. Abnormal expression of miR-29a has been found in several types of cancers, including melanoma. In this study, experiments were performed to investigate the role of miR-29a in melanoma, and the molecular mechanism by which miR-29a represses melanoma. Methods: miR-29 and Bmi1 expression was examined by quantitative real-time polymerase chain reaction (qRT-PCR). The cell viability, apoptosis, migration and invasion were respectively determined by Cell Counting Kit-8 assay, Propidium iodide (PI) fluorescein isothiocynate (FITC)-Annexin V staining assay, wound healing assay and transwell assay. Luciferase reporter assay was performed to determine a target gene of miR-29a. Western blot was used to analyze protein expression of apoptosis-related proteins, Bmi1, Wnt/β-catenin and Nuclear factor-κB (NF-κB) pathway target genes. Results: miR-29a was down-regulated in all tested melanoma cell lines. Up-regulation of miR-29a effectively inhibited cell viability, migration, and invasion, but promoted apoptosis in A375 cells. Bmi1 was a direct target gene of miR-29a. Transfection with miR-29a mimic decreased cell migration and invasion and Bmi1 expression in Malme-3M cells, SK-MEL-2, SK-MEL-5, and M14 cell lines. Moreover, miR-29a might suppress growth, migration and invasion of A375 cells by negatively regulating Bmi1. In addition, our results demonstrated that transfection with miR-29a mimic effectively blocked Wnt/β-catenin and NF-κB pathways via down-regulating Bmi1. Conclusion: miR-29a could be functioned as a potential tumor suppressor through direct regulation of Bmi1 in melanoma cells.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MicroRNA-29a Inhibits Growth, Migration and Invasion of Melanoma A375 Cells in Vitro by Directly Targeting BMI1

Xiong

Liu

Qiu

et al. 2018

Cell Physiol Biochem

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“…Like many well-defined miRNAs, the diverse target genes of miR-211 have been identified and characterized, including PP2Cm [18], Cyclin D1, CDK6 [27], SATB2 [28], CDC25B [29], NUAK1 [30], TGFβR II [31], CHD5 [32] and BRN2 [33]. Based on our preliminary finding, we employed the miRanda algorithm [19] to analyze the potential regulatory effect of miR-211-5p on IL-10.…”

Section: Discussionmentioning

confidence: 99%

NF-κB-Induced MicroRNA-211 Inhibits Interleukin-10 in Macrophages of Rats with Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome

Wang

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: The present study addressed the potential involvement of microRNAs in acute respiratory distress syndrome (ARDS)-related inflammation and elucidates the underlying molecular mechanism. Methods: ARDS rat model was established by lipopolysaccharide, with compromised gas exchange capacity and lung edema. The inflammatory cells from bronchoalveolar lavage fluid (BALF) were profiled with automatic blood cell analyzer. The relative fluorescence intensity of BALF-derived macrophages was analyzed by flow cytometry. The relative microRNA expression was determined using microarray and Taqman assay. The secretory interleukin (IL)-10 was measured by enzyme-linked immunosorbent assay. Luciferase reporter assay was performed to determine the regulatory effects of miR-211 and NF-κB on IL-10 and miR-211 expressions, respectively. Chromatin immunoprecipitation (ChIP) was conducted to detect the direct binding of NK-κB on miR-211 promoter. The protein level was determined by Western blot. Results: The provoked acute inflammation was characterized with increased total cells, macrophages, neutrophils and lymphocytes. The relative expression of miR-211 was aberrantly up-regulated in BALF-derived macrophages from ARDS rats, which was accompanied with reduction of secretory IL-10. We further demonstrated that miR-211 inhibited IL-10 expression by binding to its 3’-UTR. The expression of miR-211 was modulated by NF-κB. Conclusion: Here we elucidated a crucial role of NF-κB/miR-211/IL-10 signaling axis in ARDS-related inflammation.

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“…miR-211 has several putative target genes, including the calcium-activated potassium channel subunit ␣-1 gene (KCNMA1), the insulin-like growth factor 2 receptor gene (IGF2R), the transforming growth factor ␤ receptor 2 gene (TGFBR2), the insulin growth factor binding protein 5 gene (IGFBP5), the POU domain-containing transcription factor gene BRN2, the nuclear factor of activated T cells 5 gene (NFAT5), and NAUK1 (10,13,17,18).…”

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confidence: 99%

MicroRNA 211 Functions as a Metabolic Switch in Human Melanoma Cells

Mazar

Lee

et al. 2016

Molecular and Cellular Biology

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bMicroRNA 211 (miR-211) negatively regulates genes that drive invasion of metastatic melanoma. Compared to normal human melanocytes, miR-211 expression is significantly reduced or absent in nonpigmented melanoma cells and lost during human melanoma progression. To investigate the molecular mechanism of its tumor suppressor function, miR-211 was ectopically expressed in nonpigmented melanoma cells. Ectopic expression of miR-211 reduced hypoxia-inducible factor 1␣ (HIF-1␣) protein levels and decreased cell growth during hypoxia. HIF-1␣ protein loss was correlated with the downregulation of a miR-211 target gene, pyruvate dehydrogenase kinase 4 (PDK4). We present evidence that resumption of miR-211-mediated downregulation of PDK4 in melanoma cells causes inhibition of invasion by nonpigmented melanomas via HIF-1␣ protein destabilization. Thus, the tumor suppressor miR-211 acts as a metabolic switch, and its loss is expected to promote cancer hallmarks in human melanomas. Melanoma, one of the deadliest forms of skin cancer, kills nearly 10,000 people in the United States per year. We had previously shown that a small noncoding RNA, termed miR-211, suppresses invasion and the growth of aggressive melanoma cells. The results presented here support the hypothesis that miR-211 loss in melanoma cells causes abnormal regulation of energy metabolism, which in turn allows cancer cells to survive under low oxygen concentrations-a condition that generally kills normal cells. These findings highlight a novel mechanism of melanoma formation: miR-211 is a molecular switch that is turned off in melanoma cells, raising the hope that in the future we might be able to turn the switch back on, thus providing a better treatment option for melanoma.

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Transcription Factor/microRNA Axis Blocks Melanoma Invasion Program by miR-211 Targeting NUAK1

Cited by 109 publications

References 66 publications

MicroRNA-29a Inhibits Growth, Migration and Invasion of Melanoma A375 Cells in Vitro by Directly Targeting BMI1

MicroRNA-29a Inhibits Growth, Migration and Invasion of Melanoma A375 Cells in Vitro by Directly Targeting BMI1

NF-κB-Induced MicroRNA-211 Inhibits Interleukin-10 in Macrophages of Rats with Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome

MicroRNA 211 Functions as a Metabolic Switch in Human Melanoma Cells

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