MicroRNA-26b inhibits tumor metastasis by targeting the KPNA2/c-jun pathway in human gastric cancer

Tsai, Ming-Ming; Huang, Hsiang-Wei; Wang, Chia‐Siu; Lee, Kam-Fai; Tsai, Chung‐Ying; Lu, Pei-Hsuan; Chi, Hsiang-Cheng; Lin, Yang-Hsiang; Kuo, Liang-Mou; Lin, Kwang‐Huei

doi:10.18632/oncotarget.8629

Cited by 52 publications

(38 citation statements)

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“…Similarly, the inhibitory roles of various miRNAs in tumor growth and metastasis have been demonstrated in previous NSCLC studies [ 30 , 38 , 39 ]. Furthermore, upregulation of miR-26b leads to inhibition of gastric cancer cell migration and invasion in vitro and lung metastasis formation in vivo [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

miR-4317 suppresses non-small cell lung cancer (NSCLC) by targeting fibroblast growth factor 9 (FGF9) and cyclin D2 (CCND2)

Chen

Zhao

et al. 2018

J Exp Clin Cancer Res

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BackgroundNon-small cell lung cancer (NSCLC) is a leading cause of death worldwide. MicroRNAs (miRNAs) have been indicated as crucial actors in cancer biology. Accumulating evidence suggests that miRNAs can be used as diagnostic and prognostic markers for NSCLC.MethodsThe purpose of this study was to characterize and identify the novel biomarker miR-4317 and its targets in NSCLC. The expression of miR-4317 was analyzed by in situ hybridization (ISH) and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The effect of miR-4317 on proliferation was evaluated through 3–4,5-dimethylthiazol-2-yl-5-3–carboxymethoxyphenyl-2-4-sulfophenyl-2H-tetrazolium (MTS) and colony formation assays, and cell migration and invasion were evaluated through transwell assays. The expression of target proteins and downstream molecules was analyzed by qRT-PCR and western blot. Dual-luciferase reporter assay was used to assess the target genes of miR4317 in NSCLC cells.ResultsOur results demonstrated that miR-4317 was downregulated in NSCLC tissues and serum, particularly in lymph node metastasis and advanced clinical stage tissues. Kaplan-Meier survival analysis showed that NSCLC patients with high expression of miR-4317 exhibited better overall survival (OS). Enhanced expression of miR-4317 significantly inhibited proliferation, colony formation, migration and invasion, and hampered cycles of NSCLC cell lines in vitro. Our results suggested that miR-4317 functions by directly targeting fibroblast growth factor 9 (FGF9) and cyclin D2 (CCND2). In concordance with in vitro studies, mouse xenograft, lung, and brain metastatic studies validated that miR-4317 functions as a potent suppressor miRNA of NSCLC in vivo. Systemically delivered agomiR-4317 reduced tumor growth and inhibited FGF9 and CCND2 protein expression. Reintroduction of FGF9 and CCND2 attenuated miR-4317-mediated suppression of migration and invasion in NSCLC.ConclusionsOur results indicate that miR-4317 can reduce NSCLC cell growth and metastasis by targeting FGF9 and CCND2. These findings provide new evidence of miR-4317 as a potential non-invasive biomarker and therapeutic target for NSCLC.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0882-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

miR-4317 suppresses non-small cell lung cancer (NSCLC) by targeting fibroblast growth factor 9 (FGF9) and cyclin D2 (CCND2)

Chen

Zhao

et al. 2018

J Exp Clin Cancer Res

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“…Additionally, miR-26a functions in cardiovascular diseases by controlling multiple signaling pathways related to angiogenesis, endothelial cell growth, and left ventricle function after myocardial infarction. Analysis of miR-26 family members in different types of cardiac cells [52-54], including endothelial cells, vascular smooth muscle cells, cardiomyocytes, and cardiac fibroblasts, has shown that miR-26 may have important functions in various cardiovascular repair mechanisms [55, 56]. Intriguingly, miR-26a has was also been found to negatively regulate glycogen synthase kinase (GSK) 3β expression, thereby altering Wnt signaling by modulating the levels of β-catenin and its downstream target C/EBPα during osteogenesis differentiation [57, 58].…”

Section: Mirna Biogenesis and Functionmentioning

confidence: 99%

MicroRNA-26a: An Emerging Regulator of Renal Biology and Disease

Pan

et al. 2019

Kidney Blood Press Res

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MicroRNAs (miRNAs) are short, single-stranded, noncoding RNAs that modulate many key biological processes by simultaneously suppressing multiple target genes. Among them, miR-26a, a conserved miRNA among vertebrates, is highly expressed in various tissues. Accumulating evidence demonstrates that miR-26a plays pivotal roles in cellular differentiation, cell growth, apoptosis, and metastasis, thereby participating in the initiation and development of various human diseases, such as metabolic disease and cancer. More recently, miR-26a was found as a versatile regulator of renal biology and disease. miR-26a is intensively involved in the maintenance of podocyte homeostasis and the actin cytoskeleton. It is also able to modulate the homeostasis and function of mesangial cells. In addition, miR-26a affects the expansion of regulatory T cells in the context of ischemia-reperfusion injury and autoimmune diabetes and thus protects the renal system from immune attack. These available data strongly suggest that renal miR-26a possesses critical pathological functions and represents a potential target for renal disease therapies. This review summarizes current knowledge of miR-26a in renal biology and disease, laying the foundation for exploring its previously unknown functions and mechanisms in the renal system.

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“…NMI, another novel interactor of GART, negatively regulates epithelial-mesenchymal transitions by inhibiting p65 acetylation in the NF-Kβ pathway (166). Knockdown of KPNA2, a novel interactor of GART, suppresses the proliferative and migratory abilities of lung cancer cells and downregulation of its regulatory miRNA miR-26b enhances cell migration and invasion in vitro, and metastasis in vivo (167). One of the downstream targets of KPNA2, which is overexpressed in non-small cell lung cancer, is another novel interactor of GART called JUN, a component of the transcription factor AP-1 promoting progression of cell cycle and involved in breakdown of the ECM (168).…”

Section: Novel Interactions Of Ifnar1 and Gart May Point At The Influmentioning

confidence: 99%

Mesothelioma Interactome with 367 Novel Protein-Protein Interactions

Yanamala

Boyce

et al. 2018

Preprint

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Malignant pleural mesothelioma (MPM) is an aggressive cancer of the thorax with a median survival of one year. We constructed an 'MPM interactome' with over 300 computationally predicted PPIs and over 1300 known PPIs of 62 literature-curated genes whose activity affects MPM. Known PPIs of the 62 MPM associated genes were derived from BioGRID and HPRD databases. Novel PPIs were predicted by applying the HiPPIP algorithm, which computes features of protein pairs such as cellular localization, molecular function, biological process membership, genomic location of the gene, gene expression in microarray experiments, protein domains and tissue membership, and classifies the pairwise features as interacting or non-interacting based on a random forest model. To our satisfaction, the interactome is significantly enriched with genes differentially expressed in MPM tumors compared with normal pleura, and with other thoracic tumors. The interactome is also significantly enriched with genes whose high expression has been correlated with unfavorable prognosis in lung cancer, and with genes differentially expressed on crocidolite exposure. 28 of the interactors of MPM proteins are targets of 147 FDA-approved drugs. By comparing differential expression profiles induced by drug to profiles induced by MPM, potentially repurposable drugs are identified from this drug list. Development of PPIs of disease-specific set of genes is a powerful approach with high translational impactthe interactome is a vehicle to piece together an integrated view on how genes associated with MPM through various high throughput studies are functionally linked, leading to clinically translatable results such as clinical trials with repurposed drugs. The PPIs are made available on a webserver, called Wiki-Pi MPM at http://severus.dbmi.pitt.edu/wiki-MPM with advanced search capabilities.Recently, twenty four germline mutations were identified in 13 genes from 198 patients with malignant mesothelioma of pleural or peritoneal origin (11). Non-invasive pre-malignant phase is not seen in mesothelioma unlike other tumors, which necessitates expeditious discovery of genetic predispositions, molecular mechanisms and therapeutics for the disease (12).60% of the disease-associated missense mutations perturb protein-protein interactions (PPIs) in human genetic disorders (13). PPIs are intricately involved in biological functions and disease mechanisms, and may be exploited for drug-discovery (13). The molecular mechanisms of disease are often revealed by the PPIs of diseaseassociated genes. For example, the involvement of transcriptional deregulation in the pathogenesis of MPM was identified through mutations detected in BAP1 and its interactions with several proteins including BRCA1 revealed by co-immunoprecipitation (14). The PPI of BRCA1 with BAP1 was also central in understanding its role in growth-control pathways and cancer (15). Studies on BAP1 and BRCA1 later provided the basis for several clinical trials including testing of the drug Vinorelbine as a second...

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MicroRNA-26b inhibits tumor metastasis by targeting the KPNA2/c-jun pathway in human gastric cancer

Cited by 52 publications

References 48 publications

miR-4317 suppresses non-small cell lung cancer (NSCLC) by targeting fibroblast growth factor 9 (FGF9) and cyclin D2 (CCND2)

miR-4317 suppresses non-small cell lung cancer (NSCLC) by targeting fibroblast growth factor 9 (FGF9) and cyclin D2 (CCND2)

MicroRNA-26a: An Emerging Regulator of Renal Biology and Disease

Mesothelioma Interactome with 367 Novel Protein-Protein Interactions

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