miR-200a Inhibits Tumor Proliferation by Targeting AP-2γ in Neuroblastoma Cells

Gao, Shun-Li; Wang, Zhen; Liu, Haiying; Liu, Dan-Li; Xie, Liming; Zhang, Zhiwei

doi:10.7314/apjcp.2014.15.11.4671

Cited by 28 publications

(15 citation statements)

References 36 publications

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“…MiR-200a suppresses cell growth and migration by targeting MACC1 in hepatocellular carcinoma [43]. In neuroblastoma cells, miR-200a inhibits tumor proliferation by targeting AP-2gamma [44]. Here, we found that miR-200a significantly down-regulated HMGB1 expression in HCC cells, which inspired us to hypothesize miR-200a might play some functional roles in HCC through regulation of HMGB1.…”

Section: Discussionmentioning

confidence: 67%

The long non-coding RNA TP73-AS1 modulates HCC cell proliferation through miR-200a-dependent HMGB1/RAGE regulation

Huang

et al. 2017

J Exp Clin Cancer Res

127

115

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BackgroundP73 antisense RNA 1 T (non-protein coding), also known as TP73-AS1, is a long non-coding RNA (lncRNA) which is involved in cell proliferation and the development of tumors. However, the exact effects and molecular mechanisms of TP73-AS1 in hepatocellular carcinoma (HCC) progression are still unknown. The present study is aimed to investigate the detailed functions and the mechanism of TP73-AS1 in regulation of HCC cell proliferation.MethodsTP73-AS1 expression in HCC tissues and cell lines was determined using real-time PCR assays; the correlation of TP73-AS1 expression with clinicopathological features of HCC was analyzed. The functions of TP73-AS1 in regulation of HCC cell proliferation was evaluated using MTT and BrdU assays. The candidate upstream miRNAs of HMGB1 were screened using miRcode, miRWalk, miRanda and Target scan, verified using real-time PCR assays. The interaction between TP73-AS1 and miR-200a was confirmed using Luciferase report gene assays. The proten levels of HMGB1 signaling-related factors in response to co-processing TP73-AS1 knockdown and miR-200a inhibition were determined using Western blot assays and ELISA. Further, miR-200a, HMGB1 mRNA and RAGE mRNA and their correlations in HCC tissues were determined.ResultsTP73-AS1 was upregulated in HCC tissues and cell lines. High TP73-AS1 expression was correlated with worse clinicopathological features, poorer prognosis and shorter survival. Knockdown of TP73-AS1 inhibited the HCC proliferation and the expression levels of HMGB1, RAGE and NF-κB in HCC cells. By using online tools, we screened out several candidate upstream miRNAs of HMGB1, among which miR-200a overexpression inhibited HMGB1 mRNA expression the most significantly. By using luciferase assays, we confirmed that miR-200a could directly bind to TP73-AS1 and the 3’UTR of HMGB1; TP73-AS1 competed with HMGB1 for miR-200a binding. MiR-200a inhibition could up-regulate HMGB1, RAGE, NF-κB expression as well as NF-κB regulated cytokines levels, which could be partially restored by si-TP73-AS1. In HCC tissues, miR-200a was down-regulated while HMGB1 and RAGE were up-regulated; TP73-AS1 was inversely correlated with miR-200a, while positively correlated with HMGB1 and RAGE, respectively.ConclusionOur data indicated that TP73-AS1 might be an oncogenic lncRNA that promoted proliferation of HCC and could be regarded as a therapeutic target in human HCC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0519-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 67%

The long non-coding RNA TP73-AS1 modulates HCC cell proliferation through miR-200a-dependent HMGB1/RAGE regulation

Huang

et al. 2017

J Exp Clin Cancer Res

127

115

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“…The miR-200 family member genes are clustered at two locations in the genome: the miR-200b/200a/429 cluster and the miR-141/200c cluster [ 4 ]. The miR-200 family members repress the epithelial-to-mesenchymal transition (EMT), cancer cell migration, tumor growth, and metastasis by directly targeting specific genes, such as ZEB1, Suz12, moesin, and AP-2γ [ 4 , 5 ]. In contrast, the miR-200 family members have been shown to enhance the migration ability of breast cancer cells and to promote the metastatic colonization of breast cancer cells through up-regulating the expression of E-cadherin and down-regulating that of ZEB2 and Sec23a [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of the miR-141/200c cluster promotes the migratory and invasive ability of triple-negative breast cancer cells through the activation of the FAK and PI3K/AKT signaling pathways by secreting VEGF-A

et al. 2016

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BackgroundThe role of microRNA-200 (miR-200) family members in the migration and invasion of breast cancer is controversial. This study investigated the mechanisms by which the miR-200 family members modulated the migratory and invasive abilities of an aggressive triple-negative breast cancer (TNBC) cell line, MDA-MB-231.MethodsThe miR-200 family (miR-200b/200a/429 and miR-141/200c clusters) and green fluorescence protein (GFP) were transduced into MDA-MB-231 cells using a lentiviral system. Stable cells highly expressing the miR-200 family and GFP were isolated by puromycin selection and fluorescence-activated cell sorting. Gene expression was evaluated using real-time polymerase chain reaction (PCR) and reverse transcriptase-PCR (RT-PCR). The migratory and invasive abilities were assessed using trans-well and wound-healing assays. The secreted cytokines and growth factors in cultured media were quantified using a Bio-Plex200 multiplex array system. Western blot assays and immunofluorescence staining were conducted to investigate miR-200 family-regulated signaling pathways. The entire dataset obtained in this study was statistically evaluated using a one-way ANOVA followed by a t-test.ResultsThe stable overexpression of the miR-200b/200a/429 or miR-141/200c cluster suppressed cell growth and significantly increased migration and invasion of MDA-MB-231 cells. miR-141/200c overexpression was more effective in decreasing cell growth and promoting migration and invasion of MDA-MB-231 cells than was miR-200b/200a/429 overexpression. In addition, the overexpression of the miR-200b/200a/429 or miR-141/200c cluster led to an increase in the phosphorylation of focal adhesion kinase (FAK) and protein kinase B (AKT). Chemical inhibitors of FAK and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT suppressed the migration and invasion of MDA-MB-231 cells that was enhanced by the overexpression of the miR-200b/200a/429 or miR-141/200c cluster. Compared to the miR-200b/200a/429 cluster-transduced MDA-MB-231 cells, the miR-141/200c cluster-transduced MDA-MB-231 cells exhibited a significant increase in vascular endothelial growth factor (VEGF)-A secretion and integrin-alphaV (integrin-αV) expression. Treatment with an anti-VEGF-A-neutralizing antibody inhibited the increase in migration and invasion in both the miR-200b/200a/429- and miR-141/200c-transduced MDA-MB-231 cells but significantly reduced the phosphorylation of FAK and AKT in only the miR-141/200c cluster-transduced MDA-MB-231 cells.ConclusionsTaken together, our data demonstrate a mechanism in which the miR-141/200c cluster, through FAK- and PI3K/AKT-mediated signaling by means of increased VEGF-A secretion, promotes the migratory and invasive abilities of MDA-MB-231 cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2620-7) contains supplementary material, which is available to authorized users.

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“…MicroRNAs (miRNAs) are 19–22-nucleotide RNAs that regulate gene expression, primarily, posttranscriptionally, by complementary binding to the 3′-UTR of target mRNA, resulting in mRNA destabilization and/or translational inhibition [7]. Interestingly, a number of fundamental biological processes essential for the onset and development of tumors, including cell proliferation [8], cell differentiation [9], and cell invasion [10], have all been reported to be subjected to the regulation of miRNAs.…”

Section: Introductionmentioning

confidence: 99%

miR-20b Inhibits T Cell Proliferation and Activation via NFAT Signaling Pathway in Thymoma-Associated Myasthenia Gravis

Cai

et al. 2016

BioMed Research International

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Purpose. We examined the role of miR-20b in development of thymoma-associated myasthenia gravis, especially in T cell proliferation and activation. Materials and Methods. Using qRT-PCR, we assessed expression levels of miR-20b and its target genes in cultured cells and patient samples and examined the proliferation of cultured cells, using MTT cell proliferation assays and flow cytometry based cell cycle analysis. Activation of T cells was determined by both flow cytometry and qRT-PCR of activation-specific marker genes. Results. Expression of miR-20b was downregulated in samples of thymoma tissues and serum from patients with thymoma-associated myasthenia gravis. In addition, T cell proliferation and activation were inhibited by ectopic overexpression of miR-20b, which led to increased T cell proliferation and activation. NFAT5 and CAMTA1 were identified as targets of miR-20b. Expression levels of NFAT5 and CAMTA1 were inhibited by miR-20b expression in cultured cells, and the expression levels of miR-20b and NFAT5/CAMTA1 were inversely correlated in patients with thymoma-associated myasthenia gravis. Conclusion. miR-20b acts as a tumor suppressor in the development of thymoma and thymoma-associated myasthenia gravis. The tumor suppressive function of miR-20b in thymoma could be due to its inhibition of NFAT signaling by repression of NFAT5 and CAMTA1 expression.

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miR-200a Inhibits Tumor Proliferation by Targeting AP-2γ in Neuroblastoma Cells

Cited by 28 publications

References 36 publications

The long non-coding RNA TP73-AS1 modulates HCC cell proliferation through miR-200a-dependent HMGB1/RAGE regulation

The long non-coding RNA TP73-AS1 modulates HCC cell proliferation through miR-200a-dependent HMGB1/RAGE regulation

Overexpression of the miR-141/200c cluster promotes the migratory and invasive ability of triple-negative breast cancer cells through the activation of the FAK and PI3K/AKT signaling pathways by secreting VEGF-A

miR-20b Inhibits T Cell Proliferation and Activation via NFAT Signaling Pathway in Thymoma-Associated Myasthenia Gravis

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