MicroRNA-9 suppresses uveal melanoma cell migration and invasion through the NF-κB1 pathway

Liu, Nannan; Sun, Qingmin; Chen, Jie; Li, Jiaqi; Zeng, Ying; Zhai, Sulan; Li, Ping; Wang, Bin; Wang, Xuerong

doi:10.3892/or.2012.1905

Cited by 42 publications

(31 citation statements)

References 27 publications

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“…The regulation of CXCR4 by miR‐9 has also been invoked to explain the effect of miR‐9 on cell growth (Yu et al ., 2013). In addition, miR‐9 can regulate NF‐KB1 , affecting cell migration (Liu et al ., 2012), and E–cadherin (Ma et al ., 2010), explaining its role in regulating metastatic growth. It would clearly be interesting to determine how the regulatory module involving CBX7 and miR‐9 contributes to these physiological processes and whether it influences aging.…”

Section: Discussionmentioning

confidence: 99%

CBX7 and miR‐9 are part of an autoregulatory loop controlling p16^INK^4a

et al. 2015

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SummaryPolycomb repressive complexes (PRC1 and PRC2) are epigenetic regulators that act in coordination to influence multiple cellular processes including pluripotency, differentiation, cancer and senescence. The role of PRCs in senescence can be mostly explained by their ability to repress the INK4/ARF locus. CBX7 is one of five mammalian orthologues of Drosophila Polycomb that forms part of PRC1. Despite the relevance of CBX7 for regulating senescence and pluripotency, we have a limited understanding of how the expression of CBX7 is regulated. Here we report that the miR‐9 family of microRNAs (miRNAS) downregulates the expression of CBX7. In turn, CBX7 represses miR‐9‐1 and miR‐9‐2 as part of a regulatory negative feedback loop. The miR‐9/CBX7 feedback loop is a regulatory module contributing to induction of the cyclin‐dependent kinase inhibitor (CDKI) p16INK 4a during senescence. The ability of the miR‐9 family to regulate senescence could have implications for understanding the role of miR‐9 in cancer and aging.

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Section: Discussionmentioning

confidence: 99%

CBX7 and miR‐9 are part of an autoregulatory loop controlling p16^INK^4a

et al. 2015

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“…According to computational prediction, NF-κB and Mcl-1 are the candidate target genes for mR-9-3 and miR-193a, respectively (Fig. 6), and NF-κB has been established as a target gene for miR-9 [34,35] and Mcl-1 as a target gene for miR-193a [36,37]. Reciprocal relationships in terms of their expression levels between miR-9-3 and NF-κB, and between miR-193a and Mcl-1 were consistently observed.…”

Section: Resultsmentioning

confidence: 99%

Demethylation of miR-9-3 and miR-193a Genes Suppresses Proliferation and Promotes Apoptosis in Non-Small Cell Lung Cancer Cell Lines

Wang

Yang

Han

et al. 2013

Cell Physiol Biochem

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Background: MicroRNAs miR-9-3 and miR-193a have recently been found to be hypermethylated in a variety of non-small cell lung cancer (NSCLC) cells and primary human tumors. The objectives of this study were to investigate the role of demethylation of miR-9-3 and miR-193a genes in regulating proliferation and apoptosis in NSCLCs, and to decipher the potential mechanisms underlying the properties. Methods: MTT and population doubling time by flow cytometry were used to assess cell proliferation. Enzyme-Linked Immunosorbent Assay and caspase-3 activity assay were employed to evaluate apoptosis. Real-time RT-PCR and Western blot were used to quantify gene expression at mRNA and protein levels, respectively. Methylation-specific PCR was utilized to assess methylation status. Results: We found that demethylation agent 5-Aza-2'-deoxycytidine (5-AzaC) reduced cell numbers and prolonged population doubling time (PDT), and promoted doxorubicin-induced apoptosis in seven NSCLC cell lines with different methylation statuses on miR-9-3 and miR-193a promoter regions: NCI-H1993/NCI-H1915 (miR-9-3⁺/miR-193a⁺), NCI-H1975/NCI-H200 (miR-9-3⁺/miR-193a^-), A427/NCI-H2073 (miR-9-3^-/miR-193a⁺), and NCI-H1703 (miR-9-3^-/miR-193a^-). Treatment with 5-AzaC concomitantly upregulated expression of miR-9-3 and miR-193a, and downregulated their respective target genes NF-κB and Mcl-1. The effects of 5-AzaC were abolished by concomitant knockdown of miR-9-3 and miR-193a using the complex antisense technique, whereas forced ectopic expression of miR-9-3 and miR-193a mimicked the effects of 5-AzaC. We further observed that the strength of proliferation inhibition and apoptosis promotion elicited by 5-AzaC was in the order of NCI-H1993/NCI-H1915 > A427/NCI-H2073 > NCI-H1975/NCI-H200 > NCI-H1703. Conclusions: Methylation-silencing of miR-9-3 and miR-193a may be an important epigenetic mechanisms favoring NSCLC cell growth and survival for carcinogenesis and cancer progression, and demethylation to reactivate expression of miR-9-3 and miR-193a genes contributes, at least partially, to the anti-cancer properties of 5-AzaC and thereby may be worthy of future studies for the possibility of being a new therapeutic strategy for the treatment of human NSCLCs.

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“…Subsequently, miR-9 overexpression suppressed the invasion, metastasis, and angiogenesis of these cells in vitro and in vivo [95]. In uveal melanoma, miR-9 suppresses migration and invasion of highly invasive cells by modulating the NFκB pathway, including notably the matrix metalloproteinases MMP-2 and MMP-9 and the angiogenesis-related protein VEGF-A[96]. A suppressive effect of miR-9 on metastasis was shown in vitro and in vivo in gastric cancer cells, exerted via the targeting of cyclin D1, the transcription factor Ets1 and their downstream targets of which MMP-9[97].…”

Section: Mirnas and Metastasismentioning

confidence: 99%

Regulation of microRNAs in cancer metastasis

Bouyssou

Manier

Huynh

et al. 2014

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

133

129

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Metastasis is a phenomenon of crucial importance in defining prognosis in patients with cancer and is often responsible for cancer-related mortality. It is known that several steps are necessary for clonal cells to disseminate from their primary tumor site and colonize distant tissues, thus originating metastatic lesions. Therefore, investigating the molecular actors regulating this process may provide helpful insights in the development of efficient therapeutic responses. Recent evidences have indicated the role of microRNAs (miRNAs) in modulating the metastatic process in solid tumors. miRNAs are small regulatory non-coding RNAs that bind specific target mRNAs, leading to translational repression. miRNAs are known to act as negative regulators of gene expression and are involved in the regulation of biological processes, including cell growth, differentiation and apoptosis, both in physiological conditions and during diseases, such as tumors. In the specific field of tumorigenesis, miRNAs play an important role in mediating oncogenesis and favoring tumor progression, as a result of their ability to modulate epithelial-to-mesenchymal transition (EMT) and other series of events facilitating the formation of metastasis. The role of miRNAs in cancer development has been widely studied and has helped elucidate events such as the change in expression of oncogenes, tumor-suppressors and cancer-related proteins. This review focuses on the mechanisms underlying the role of miRNAs as part of the metastatic process.

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MicroRNA-9 suppresses uveal melanoma cell migration and invasion through the NF-κB1 pathway

Cited by 42 publications

References 27 publications

CBX7 and miR‐9 are part of an autoregulatory loop controlling p16^INK^4a

CBX7 and miR‐9 are part of an autoregulatory loop controlling p16^INK^4a

Demethylation of miR-9-3 and miR-193a Genes Suppresses Proliferation and Promotes Apoptosis in Non-Small Cell Lung Cancer Cell Lines

Regulation of microRNAs in cancer metastasis

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MicroRNA-9 suppresses uveal melanoma cell migration and invasion through the NF-κB1 pathway

Cited by 42 publications

References 27 publications

CBX7 and miR‐9 are part of an autoregulatory loop controlling p16INK4a

CBX7 and miR‐9 are part of an autoregulatory loop controlling p16INK4a

Demethylation of miR-9-3 and miR-193a Genes Suppresses Proliferation and Promotes Apoptosis in Non-Small Cell Lung Cancer Cell Lines

Regulation of microRNAs in cancer metastasis

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CBX7 and miR‐9 are part of an autoregulatory loop controlling p16^INK^4a

CBX7 and miR‐9 are part of an autoregulatory loop controlling p16^INK^4a