MicroRNA-155 Targets SMAD2 and Modulates the Response of Macrophages to Transforming Growth Factor-β

Louafi, Fethi; Martínez-Nuñez, Rocío T.; Sánchez-Elsner, Tilman

doi:10.1074/jbc.m110.146852

Cited by 183 publications

(163 citation statements)

References 36 publications

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“…Among these genes, SMAD family member 2 (SMAD2), one of the mediators of TGF-β signaling, was predicted to have two putative miR-155 binding sites within its 3'UTR by both TargetScan and Microrna.org. In addition, SMAD2 was validated as a target gene of miR-155 in macrophages (23). Therefore, we further confirmed whether SMAD2 was also the authentic target gene of miR-155 in gastric cancer.…”

Section: Mir-155 Targetting 3'utr Of the Smad2 Gene Since Mir-155supporting

confidence: 67%

microRNA-155 is downregulated in gastric cancer cells and involved in cell metastasis

Nie

Wang

et al. 2012

Oncol Rep

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Abstract. , an important multifunctional microRNA, has been implicated in the development of multiple solid tumors, yet, its role in gastric cancer cells has not been fully elucidated. In this study, we find that miR-155 was significantly downregulated in gastric cancer cell lines compared with an immortalized gastric epithelial cell line (GES-1). Overexpression of miR-155 in SGC-7901 and MKN-45 gastric cancer cells dramatically suppressed cell migration, invasion and adhesion in vitro. Overexpression of miR-155 significantly reduced the protein levels of SMAD2 and repressed the activity of a luciferase reporter containing one of the two predicted miR-155 binding sites in SMAD2 3'-UTR, indicating that SMAD2 may be a miR-155 target gene. miR-155 expression was also remarkably restored by a DNA demethylating agent (5-Aza-2-deoxycytidine) in SGC-7901 and MKN-45 gastric cancer cells. Taken together, these data suggest that miR-155 may function as a tumor suppressor to regulate gastric cancer cell metastasis by targeting SMAD2, and its downregulation in gastric cancer cells may be partly ascribed to DNA methylation. IntroductionGastric cancer remains the fourth most common malignancy and the second leading cause of cancer-related death in both genders worldwide, despite a substantial decrease in its rate (1,2). In 2008, more than 70% of new cases (713,000 cases) occurred in developing countries, and half the world total occured in Eastern Asia (mainly in China) (2). Despite a steady decline in mortality, the prognosis of patients with advanced gastric cancer is still very disappointing (3), mainly due to poor understanding of the mechanisms underlying its development. microRNAs (miRNAs) are endogenous, small (18-25 nucleotides), non-coding RNAs that play important roles in gene expression by targeting 3'UTR of cellular transcripts, resulting mRNA cleavage or translational inhibition (4,5). By these mechanisms, miRNAs have been shown to be involved in mediating processes in tumorigenesis such as cell cycle regulation, differentiation, apoptosis, invasion and metastasis (6,7). Dysregulated expression of miRNAs is now considered as a common characteristic of all human tumors (8). The aberrant expression of miRNAs in human cancers and their role in tumor formation might define miRNAs as oncogenes or tumor suppressors.miR-155, processed from an exon of a non-coding RNA transcribed from the B-cell integration cluster (BIC), has been a typical multifunctional miRNA (9,10). Accumulating evidence has demonstrated that miR-155 is involved in numerous biological processes including haematopoiesis, inflammation, immunity and carcinogenesis (10,11). Several lines of evidence indicate that dysregulation of miR-155 is linked to various solid tumors, including breast, colon, cervical, thyroid, pancreatic and lung cancer (12-18). The frequently detected overexpression of miR-155 in these tumors indicates a major role of an oncogene; however, possible tumor suppressor functions have also been reported (19-21). Although miR-155 has bee...

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Section: Mir-155 Targetting 3'utr Of the Smad2 Gene Since Mir-155supporting

confidence: 67%

microRNA-155 is downregulated in gastric cancer cells and involved in cell metastasis

Nie

Wang

et al. 2012

Oncol Rep

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“…48,49 These findings suggest a potential role for miRNA modulation in controlling gene expression in epithelial cells and, thus, regulating fibrosis. Our data demonstrate a role for miR-155 in negatively regulating KGF during lung repair after influenza infection, suggesting a pathogenic role.…”

Section: Recovery From Influenza Infectionmentioning

confidence: 95%

Epigenetic and Transcriptomic Regulation of Lung Repair during Recovery from Influenza Infection

Pociask

Robinson

Chen

et al. 2017

The American Journal of Pathology

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Seasonal and pandemic influenza is a cause of morbidity and mortality worldwide. Most people infected with influenza virus display mild-to-moderate disease phenotypes and recover within a few weeks. Influenza is known to cause persistent alveolitis in animal models; however, little is known about the molecular pathways involved in this phenotype. We challenged C57BL/6 mice with influenza A/PR/8/34 and examined lung pathologic processes and inflammation, as well as transcriptomic and epigenetic changes at 21 to 60 days after infection. Influenza induced persistent parenchymal lung inflammation, alveolar epithelial metaplasia, and epithelial endoplasmic reticulum stress that were evident after the clearance of virus and resolution of morbidity. Influenza infection induced robust changes in the lung transcriptome, including a significant impact on inflammatory and extracellular matrix protein expression. Despite the robust changes in lung gene expression, preceding influenza (21 days) did not exacerbate secondary Staphylococcus aureus infection. Finally, we examined the impact of influenza on miRNA expression in the lung and found an increase in miR-155. miR-155 knockout mice recovered from influenza infection faster than controls and had decreased lung inflammation and endoplasmic reticulum stress. These data illuminate the dynamic molecular changes in the lung in the weeks after influenza infection and characterize the repair process, identifying a novel role for miR-155. (Am J Pathol 2017, 187: 851e863; http://dx

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“…22 Therefore, in different physiological and pathological conditions, miR-155 might only directly inhibit certain transcripts and could play quite a different role in the differentiation of each Th cell subset. Smaand Mad-related protein 2 and suppressor of cytokine signaling 1, which are confirmed targets of miR-155, 34,35 may regulate Th17 cell differentiation in the opposite way. Sma-and Mad-related protein 2, which is essential for TGF-b signaling, induces the generation of Th17 cells, 36 whereas suppressor of cytokine signaling 1 negatively regulates Th17 cell differentiation by inhibiting the IL-6/STAT3 signaling pathway.…”

Section: Figurementioning

confidence: 98%

The altered expression of inflammation-related microRNAs with microRNA-155 expression correlates with Th17 differentiation in patients with acute coronary syndrome

Yao

et al. 2011

Cell Mol Immunol

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MicroRNAs (miRNAs) are a novel class of small, non-coding RNAs that play a significant role in both inflammatory and cardiovascular diseases. Immune cells, especially T helper (Th) cells, are critical in the development of atherosclerosis and the onset of acute coronary syndrome (ACS). To assess whether inflammation-related miRNAs (such as miR-155, 146a, 21, 125a-5p, 125b, 31) are involved in the imbalance of Th cell subsets in patients with ACS, we measured the expression of related miRNAs in patients with acute myocardial infarction (AMI), unstable angina (UA), stable angina (SA) and chest pain syndrome (CPS); analyzed the relationship between miRNA expression and the frequency of Th cell subsets; and observed the co-expression of miR-155 and IL-17A in peripheral blood mononuclear cells (PBMCs) of patients with ACS. The results showed that the expression of miR-155 in the PBMCs of patients with ACS was decreased by approximately 60%, while the expression of both miR-21 and miR-146a was increased by approximately twofold. The expression patterns of miRNAs in plasma correlated with those in PBMCs, except for miR-21, which was increased by approximately sixfold in the AMI group and showed no significant difference between the UA group and the CPS group. We also found that the expression of miR-155 inversely correlated with the frequency of Th17 cells (r520.896, P,0.01) and that miR-155 was co-expressed with IL-17A in patients with ACS. In conclusion, our study revealed the expression patterns of inflammation-related miRNAs in patients with ACS and found that miR-155 may be associated with Th17 cell differentiation.

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MicroRNA-155 Targets SMAD2 and Modulates the Response of Macrophages to Transforming Growth Factor-β

Cited by 183 publications

References 36 publications

microRNA-155 is downregulated in gastric cancer cells and involved in cell metastasis

microRNA-155 is downregulated in gastric cancer cells and involved in cell metastasis

Epigenetic and Transcriptomic Regulation of Lung Repair during Recovery from Influenza Infection

The altered expression of inflammation-related microRNAs with microRNA-155 expression correlates with Th17 differentiation in patients with acute coronary syndrome

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