Concurrent Suppression of Integrin α5, Radixin, and RhoA Phenocopies the Effects of miR-31 on Metastasis

Valastyan, Scott; Chang, Anna; Benaich, Nathan; Reinhardt, Ferenc; Weinberg, Robert A.

doi:10.1158/0008-5472.can-10-0410

Cited by 103 publications

(82 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Enforced expression of miR-409 could suppress the migration, invasion and metastasis of GC cells in vitro and in vivo. We further identified RDX, a putative pro-metastatic gene, 20,25 as a direct functional target of miR-409. To our knowledge, this is the first study to explore the role of miR-409 in cancer, and our results indicate that miR-409 acts to suppress metastasis in GC.…”

Section: Discussionmentioning

confidence: 99%

“…21 RDX was originally identified as a constituent of adherence junctions in the livers of rats, 36 and it has more recently been implicated in cancer progression and metastasis. 20,24,25,39 It has been reported that RDX may cooperate with ITGA5 and RhoA to affect three distinct steps in the invasionmetastasis cascade in vivo, local invasion, early post-intravasation events and metastatic colonisation. 25 Silencing of RDX has also been found to suppress the migration and invasion of GC cells.…”

Section: Discussionmentioning

confidence: 99%

“…20,24,25,39 It has been reported that RDX may cooperate with ITGA5 and RhoA to affect three distinct steps in the invasionmetastasis cascade in vivo, local invasion, early post-intravasation events and metastatic colonisation. 25 Silencing of RDX has also been found to suppress the migration and invasion of GC cells. 40 Together with our findings, these results suggested that RDX could act as a pro-metastatic factor in various cancers.…”

Section: Discussionmentioning

confidence: 99%

“…20,24,25 To determine whether downregulation of RDX was involved in miR-409-mediated suppression of migration and invasion, we first analysed the effects of RDX in GC cells. As shown in Figures 6a and b, transfection of a specific small interfering RNA against RDX into SGC-7901 and HGC-27 cells led to sharply decreased RDX expression.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

MicroRNA-409 suppresses tumour cell invasion and metastasis by directly targeting radixin in gastric cancers

et al. 2011

View full text Add to dashboard Cite

Emerging evidence has shown that aberrantly expressed microRNAs (miRNAs) are highly associated with tumour development and progression. However, little is known about the potential role of miRNAs in gastric cancer (GC) metastasis. In this study, miR-409-3p was found to be downregulated frequently in human GCs, and its expression was significantly associated with tumor-node-metastasis (TNM) stage and lymph node metastasis. Enforced expression of miR-409 in GC cells significantly reduced their migration and invasion in vitro and their capacity to develop distal pulmonary metastases and peritoneal dissemination in vivo. Moreover, we found that miR-409 exerted its function predominantly through the mature miR-409-3p, but not miR-409-5p. Microarray and bioinformatics analysis identified the pro-metastatic gene radixin (RDX) as a potential miR-409-3p target. Further studies confirmed that miR-409-3p suppressed the expression of RDX by directly binding to its 3 0 -untranslated region. Silencing of RDX by small interfering RNAs phenocopied the effects of miR-409 overexpression, whereas restoration of RDX in miR-409-overexpressed GC cells reversed the suppressive effects of miR-409. Taken together, these results demonstrate that miR-409 suppresses GC cell invasion and metastasis by directly targeting RDX and that patients with downregulated miR-409-3p are prone to lymph node metastasis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

MicroRNA-409 suppresses tumour cell invasion and metastasis by directly targeting radixin in gastric cancers

et al. 2011

View full text Add to dashboard Cite

show abstract

“…After potential target genes were uncovered via bioinformatic analysis, two tumor suppressor genes were found: LAST2 and PPP2R2A [58]. Further, when targeting ITGA5, RDX and RhoA, miR-31 may induce the recession of cancer cell metastasis and show suppressive tendencies [59].…”

Section: Some Mirnas That Show Both Oncogenic and Suppression Actionsmentioning

confidence: 99%

Effect of miRNAs in lung cancer suppression and oncogenesis

Zhang

Liu

2016

Open Life Sciences

View full text Add to dashboard Cite

MicroRNA (miRNAs) is a group of small noncoding RNAs. It is involved in multiple cellular processes including proliferation, development, metabolism, differentiation and apoptosis; many of which are linked to several pathological conditions, including cancer. Lung cancer is one of the leading causes of mortality in the world: in 2008 for example, there were 163,000 deaths as a result of lung cancer. Despite technologies emerging which provide the potential for novel targeted therapies and improved early diagnoses, the overall rate of fiveyear survival still remains at only 15%. One reason for this disappointing statistic is related to the presentation of the disease, and specifically a lack of markers for early detection. Notably, the expression of some miRNAs has been reported to be involved in the diagnosis, classification and even prognosis of lung cancer. Tumorsuppressive and oncogenic miRNAs were found in lung carcinogenesis and the biological functions of these miRNAs have been validated in transplantable lung cancer models and human paired normal-malignant lung tissue banks. Some of these tumor-suppressive and oncogenic miRNAs related to lung cancer will be reviewed here. This article will focus on emphasing miRNAs effectiveness as a biomarker in lung carcinogenesis and candidate pharmacology. Furthermore, how these findings improve our understanding of lung cancer biology and therapy will also be discussed.

show abstract

Cross‐regulation between cytokine and microRNA pathways in T cells

et al. 2015

View full text Add to dashboard Cite

microRNA (miRNA) mediated regulation of protein expression has emerged as an important mechanism in T-cell physiology, from development and survival to activation, proliferation, and differentiation. One of the major classes of proteins involved in these processes are cytokines, which are both key input signals and major products of T-cell function. Here, we summarize the current data on the molecular cross-talk between cytokines and miRNAs: how cytokines regulate miRNA expression, and how specific miRNAs control cytokine production in T cells. We also describe the inflammatory consequences of deregulating the miRNA/cytokine axis in mice and humans. We believe this topical area will have key implications for immune modulation and treatment of autoimmune pathology. Keywords:Cytokines r Inflammation r miRNA r T cells microRNAs as regulators of protein expressionBiological processes require the integration of environmental stimuli at the level of gene expression. The robustness of genetic networks depends on the distinction between physiological responses (to particular cues) and biological "noise" (stochastic variations), which can be achieved, for example, by establishing feed-forward transcriptional loops. Over the past two decades, a new mechanism that interacts with transcriptional loops and sets additional thresholds, which enable cells to filter physiological signals from noise has emerged; this mechanism regulates gene expression at the posttranscriptional level and relies on microRNAs (miRNAs; reviewed in [1]). These are an abundant class of evolutionarily conserved small noncoding (untranslated) RNA species that control target mRNA stability, degradation, and translation, thus affecting the majority of mammalian genes [2].Correspondence: Dr. Anita Q. Gomes e-mail: anitagomes@medicina.ulisboa.ptIn the conventional miRNA biogenesis pathway, RNA polymerase II transcribed pri-miRNAs are processed by the nuclear RNase III enzyme Drosha (complexed with DGCR8) to generate 60-70 nt stem-loop intermediates, the pre-miRNAs, that are further processed into 19-24mers in the cytoplasm by another key RNase III, Dicer. Mature miRNAs are then incorporated into RNAinduced silencing complexes, whose core components are proteins of the Argonaute family (Ago1-4), which use the 5 end (nucleotides 2-8) "seed sequence" of the miRNA to recognize complementary mRNA transcripts (mostly in their 3 untranslated region) for deadenylation or inhibition of translation, ultimately resulting in mRNA decapping and decay (reviewed in [3,4]).Unique spatial and temporal expression patterns in distinct hematopoietic cell lineages are suggestive of multiple roles for miRNAs in hematopoiesis, self-tolerance, and in immune responses, which have been explored over the past decade (reviewed in [5,6]). Over a 100 different miRNAs have been shown to be expressed by cells of the immune system, where * These authors contributed equally to this work as first authors. * * These authors contributed equally to this work as last authors.C 2015 WILEY-VCH Ve...

show abstract

Concurrent Suppression of Integrin α5, Radixin, and RhoA Phenocopies the Effects of miR-31 on Metastasis

Cited by 103 publications

References 15 publications

MicroRNA-409 suppresses tumour cell invasion and metastasis by directly targeting radixin in gastric cancers

MicroRNA-409 suppresses tumour cell invasion and metastasis by directly targeting radixin in gastric cancers

Effect of miRNAs in lung cancer suppression and oncogenesis

Cross‐regulation between cytokine and microRNA pathways in T cells

Contact Info

Product

Resources

About