miR-375 Regulates Invasion-Related Proteins Vimentin and L-Plastin

Jimenez, Lizandra; J, Lim; Burd, Berta; Harris, Thomas M.; Ow, Thomas J.; Kawachi, Nicole; Belbin, Thomas J.; Angeletti, Ruth Hogue; Prystowsky, Michael B.; Childs, Geoffrey; Segall, Jeffrey E.

doi:10.1016/j.ajpath.2017.02.019

Cited by 12 publications

(7 citation statements)

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“…Since matrix metalloproteinase 2 (MMP2), MMP3, and vimentin are molecular markers for the pathways involved in cell invasion and migration, 55 , 56 , 57 , 58 we looked at their expression in cells overexpressing/knocking down gene TRAF1 . We found that TRAF1 overexpression upregulated these markers ( Figure 6 C), whereas knockdown of TRAF1 downregulated these markers ( Figure 6 D).…”

Section: Resultsmentioning

confidence: 99%

Preeclampsia-Associated lncRNA INHBA-AS1 Regulates the Proliferation, Invasion, and Migration of Placental Trophoblast Cells

Jiang

Chen

Liu

et al. 2020

Molecular Therapy - Nucleic Acids

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Preeclampsia is believed to be caused by impaired placentation with insufficient trophoblast invasion, leading to impaired uterine spiral artery remodeling and angiogenesis. However, the underlying molecular mechanism remains unknown. We recently carried out transcriptome profiling of placental long noncoding RNAs (lncRNAs) and identified 383 differentially expressed lncRNAs in early-onset severe preeclampsia. Here, we are reporting our identification of lncRNA INHBA-AS1 as a potential causal factor of preeclampsia and its downstream pathways that may be involved in placentation. We found that INHBA-AS1 was upregulated in patients and positively correlated with clinical severity. We systematically searched for potential INHBA-AS1 -binding transcription factors and their targets in databases and found that the targets were enriched with differentially expressed genes in the placentae of patients. We further demonstrated that the lncRNA INHBA-AS1 inhibited the invasion and migration of trophoblast cells through restraining the transcription factor CENPB from binding to the promoter of TNF receptor-associated factor 1 ( TRAF1 ). Therefore, we have identified the dysregulated pathway “ INHBA-AS1 -CENPB-TRAF1” as a contributor to the pathogenesis of preeclampsia through prohibiting the proliferation, invasion, and migration of trophoblasts during placentation.

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Section: Resultsmentioning

confidence: 99%

Preeclampsia-Associated lncRNA INHBA-AS1 Regulates the Proliferation, Invasion, and Migration of Placental Trophoblast Cells

Jiang

Chen

Liu

et al. 2020

Molecular Therapy - Nucleic Acids

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“…miRNAs are endogenous approximately 23nt RNAs that pairing with mRNAs of protein-coding genes to guide their post-transcriptional suppression [43]. These hub genes have reported to be a direct target of several miRNAs including miR-125a-5p [44], miR-375 [45], miR-125[46],miR-183 [47]. Based on these hub genes, miRNAs (such as hsa-miR-34a-5p, hsa-miR-30d-5p, hsa-miR-27a-3p, hsa-miR-24-3p, hsa-miR-203a-3p, hsa-miR-16-5p, hsa-miR-155-5p, hsa-miR-1-3p, hsa-miR-129-2-3p and hsa-miR-124-3p) that may regulate CCC were predicted by miRNet tool.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of miRNA-mRNA Regulatory Network And Potential Drugs In Chronic Chagasic Cardiomyopathy Across Human And Mouse

Cao

Fan

et al. 2021

Preprint

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Background: Chronic chagasic cardiomyopathy (CCC) is the leading cause of heart failure in Latin America and often causes severe inflammation and fibrosis in the heart. Studies on myocardial function and its molecular mechanisms in patients with Chronic chagasic cardiomyopathy are very limited. In order to understand the development and progression of Chronic chagasic cardiomyopathy and find targets for its diagnosis and treatment, the field needs to better understand the exact molecular mechanisms involved in these processes.Methods: The mRNA microarray datasets GSE84796 (human) and GSE24088 (mouse) were obtained from the Gene Expression Omnibus (GEO) database. Homologous genes between the two species were identified using the online database mining tool Biomart, followed by differential expression analysis, gene enrichment analysis and protein-protein interaction (PPI) network construction. Cytohubba plug-in of Cytoscape software was used to identify Hub gene, and miRNet was used to construct the corresponding miRNA-mRNA regulatory network. Furthermore, Comparative Toxicogenomics Database (CTD) was used to identify hub gene-related drugs. Results: A total of 86 homologous genes were significantly differentially expressed in the two datasets, including 73 genes with high expression and 13 genes with low expression. These differentially expressed genes were mainly enriched in the terms of innate immune response, signal transduction, protein binding, Natural killer cell mediated cytotoxicity, Tuberculosis, Chemokine signaling pathway, Chagas disease and PI3K−Akt signaling pathway. The top 10 hub genes LAPTM5, LCP1, HCLS1, CORO1A, CD48, TYROBP, RAC2, ARHGDIB, FERMT3 and NCF4 were identified from the PPI network. A total of 122 miRNAs were identified to target these hub genes and 30 of them regulated two or more hub genes at the same time. Finally, 49 drugs, such as Gentamicins, acetamide, Isotretinoin, Nimesulide, Oxyquinoline, Quercetin and Resveratrol were identified to target these hub genes.Conclusions: In this study, the potential genes associated with Chronic chagasic cardiomyopathy are identified and a miRNA-mRNA regulatory network is constructed. This study explores the molecular mechanisms of Chronic chagasic cardiomyopathy and provides important clues for finding new therapeutic targets.

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“…A growing number of evidence has established that miRNAs affect cancer development by regulating vimentin. In HNSCC, miR-375 indirectly regulates vimentin mRNA levels, which is important for HNSCC invasion [ 44 ]. In colorectal cancer, miR-378 may function as a tumor suppressor and plays an important role in inhibiting tumor growth and invasion by targeting vimentin [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

MiR-876-5p modulates head and neck squamous cell carcinoma metastasis and invasion by targeting vimentin

et al. 2018

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BackgroundLocal or distant metastasis remains the main course of death in head and neck squamous cell carcinoma (HNSCC) patients. MicroRNAs (miRNAs) have been implicated in metastasis of HNSCC, but the mechanisms of their action are mainly undocumented. Through public head and neck cancer miRNA expression datasets, we found that miR-876-5p was a novel potential tumor suppressor targeting HNSCC metastasis.MethodsClinical significance and mechanism of miR-876-5P was systematically analyzed in HNSCC. Quantitative RT-PCR was used to evaluate miR-876-5p levels in HNSCC cell lines and in 20 pairs of HNSCC with associated regional nodal metastases and HNSCC without metastatic primary tumors. Scratch and invasion assays were evaluated to determine the role of miR-876-5p in the regulation of HNSCC cell migration and invasion, respectively. Western blotting was used to investigate the mechanism by which miR-876-5p suppresses HNSCC cell invasion and migration. Luciferase assays were performed to assess miR-876-5p binding to the vimentin gene. The animal model was used to support the in vitro experimental findings.ResultsMiR-876-5p mimics inhibited HNSCC cell migration and invasion. Vimentin protein and mRNA levels were decreased in the miR-876-5p mimics group but increased in the miR-876-5p inhibitors group, which demonstrated that miR-876-5p inhibits vimentin expression in HNSCC cells. By directly targeting the vimentin 3′-UTR, we used dual-luciferase reporter assays to verify that vimentin is a functional downstream target of miR-876-5p. Importantly, increased vimentin expression promoted cell migration and invasion, and co-transfection with miR-876-5p mimics and vimentin restored cell aggressiveness to the original level. Moreover, miR-876-5p overexpression significantly downregulated vimentin expression level and inhibited the distal metastasis of HNSCC cells in vivo.ConclusionsmiR-876-5p, which functions as a tumor suppressor in HNSCC, inhibits metastasis by targeting vimentin and provides a novel therapeutic target for HNSCC treatment.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0619-7) contains supplementary material, which is available to authorized users.

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miR-375 Regulates Invasion-Related Proteins Vimentin and L-Plastin

Cited by 12 publications

References 60 publications

Preeclampsia-Associated lncRNA INHBA-AS1 Regulates the Proliferation, Invasion, and Migration of Placental Trophoblast Cells

Preeclampsia-Associated lncRNA INHBA-AS1 Regulates the Proliferation, Invasion, and Migration of Placental Trophoblast Cells

Comprehensive Analysis of miRNA-mRNA Regulatory Network And Potential Drugs In Chronic Chagasic Cardiomyopathy Across Human And Mouse

MiR-876-5p modulates head and neck squamous cell carcinoma metastasis and invasion by targeting vimentin

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