MicroRNA-146a Downregulates NFκB Activity via Targeting TRAF6 and Functions as a Tumor Suppressor Having Strong Prognostic Implications in NK/T Cell Lymphoma

Paik, Jin Ho; Jang, Ji-Young; Jeon, Yoon Kyung; Kim, Wook Youn; Kim, Tae Min; Heo, Dae Seog; Kim, Chul Woo

doi:10.1158/1078-0432.ccr-11-0494

Cited by 164 publications

(159 citation statements)

References 47 publications

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“…In mice, knockout of the miR-146a gene results in the dysregulation of nuclear factor-κB (NF-κB) and then drives the development of myeloid malignancies (Zhao et al 2011). Overexpression of miR-146a can also inhibit NF-κB activity, thereby inhibiting proliferation and invasion of cancer cells as well as inducing apoptosis (Paik et al 2011;Li et al 2012a;Chen et al 2013a). However, miR-146a is upregulated in diffuse large B-cell lymphoma (Zhong et al 2012) and some invasive human breast cancer cell lines .…”

Section: Discussionmentioning

confidence: 99%

Serum Levels of miR-19b and miR-146a as Prognostic Biomarkers for Non-Small Cell Lung Cancer

Cao

et al. 2014

Tohoku J. Exp. Med.

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MicroRNA (miRNA) is a type of small non-coding RNA molecule that has important roles in cancer initiation, promotion and progression by negatively regulating gene expression. In this study, we explored the role of miRNAs in the prognosis of patients with non-small cell lung cancer (NSCLC). The miRNA expression profiles were determined in 5 pairs of NSCLC and paracancerous tissues (3 adenocarcinomas and 2 squamous cell carcinomas). Aberrantly expressed miRNAs were validated by quantitative real-time PCR (qRT-PCR) in 61 pairs of NSCLC and paracancerous tissues. Differentially expressed miRNAs were further analyzed in sera from 94 healthy subjects and 94 advanced NSCLC patients receiving platinumbased chemotherapy. Three miRNAs (miR-19b, miR-146a, and miR-223) were significantly dysregulated in NSCLC tissues (P < 0.05). High miR-19b and low miR-146a expression in NSCLC tissues were associated with higher TNM stage, lymph node metastasis and poorer survival (P < 0.05). The serum levels of miR-19b in NSCLC patients were significantly higher (P < 0.001), whereas serum levels of miR-146a were significantly lower (P < 0.001), compared with those in controls. Serum levels of miR-19b and miR-146a were associated with overall survival of NSCLC patients (P < 0.05). Patients with low serum level of miR-19b and high serum level of miR-146a achieved a higher overall response rate and longer survival time (P < 0.05). These data suggest that miR-19b and miR-146a are potential biomarkers for the prediction of survival and response to chemotherapy in NSCLC.

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Section: Discussionmentioning

confidence: 99%

Serum Levels of miR-19b and miR-146a as Prognostic Biomarkers for Non-Small Cell Lung Cancer

Cao

et al. 2014

Tohoku J. Exp. Med.

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“…Through its two targets, TRAF6 and IRAK1, miR-146a can inhibit the function of immune cell thereby affecting the human innate immune system (Taganov et al, 2006). Furthermore, the miR-146a gene was reported to down-regulate NF-κB, suppress cell proliferation, and induce apoptosis, and therefore might function as a potent tumor suppressor (Paik et al, 2011). Mutation of the miR146a gene may impair these functions; therefore the mutant allele might augment the risk of developing gastric cancer, in concordance with our results.…”

Section: Discussionmentioning

confidence: 99%

Common polymorphisms of the microRNA genes (miR-146a and miR-196a-2) and gastric cancer risk: an updated meta-analysis

Chen

Xue

2015

Genet. Mol. Res.

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ABSTRACT. The associations between two common polymorphisms in microRNA genes (miR-146a, dbSNP: rs2910164; miR-196a-2, dbSNP: rs11614913) and gastric cancer risk have frequently been examined; however, the results have often been controversial. This meta-analysis was performed to clarify the association between the two polymorphisms and gastric cancer risk. The literature search primarily utilized PubMed, Embase, SinoMed, and Wanfang databases to identify eligible studies. Odds ratios (ORs) with their 95% confidence intervals (CIs) were analyzed to investigate possible correlations. Subgroup analyses of ethnicity as well as source of controls were also performed. The correlation analysis was based on 11 studies, containing 4690 patients and 6066 controls for miR-146a (C>G) together with 1911 patients and 2484 controls for miR-196a-2 (T>C). For the miR-146a polymorphism, the values of the ORs and 95%CIs were >1, suggesting (2015) that a correlation exists. In subgroup analysis of source of controls, a correlation was also identified in the Asian subgroup. However, in Caucasians the ORs and 95%CIs were not distributed on the same side of the critical value 1, contra-indicative of a correlation in this group. For the miR-196a-2 polymorphism, the ORs with 95%CIs of both overall and subgroup analyses were also not restricted to >1 or ˂1. In summary, the results suggested that the miR-146a rs2910164 polymorphism was related to gastric cancer risk in Asians but not in Caucasians, and no distinct correlation seemed to exist between the miR-196a-2 rs11614913 polymorphism and the risk of gastric cancer.

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“…[15][16][17][18]24 miR146a has been reported to inhibit inflammation by suppressing target mRNAs, such as those encoding tumor necrosis factor receptor-associated factor 6 (TRAF6), interleukin-1 receptor-associated kinase 1 (IRAK1), and Toll-like receptor 4 (TLR4), resulting in the inhibition of NF-κB in several organs. [25][26][27][28][29] Recently, miR-146a was reported to inhibit the TGF-β 1 -Smad signaling pathway by suppressing Smad4. 30 Increased miR-146a expression has been observed in kidney samples of diabetic nephropathy patients.…”

Section: Introductionmentioning

confidence: 99%

Delivery of microRNA-146a with polyethylenimine nanoparticles inhibits renal fibrosis in vivo

Morishita¹,

Imai²,

Yoshizawa³

et al. 2015

IJN

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Renal fibrosis is the final common pathway leading to end-stage renal disease. Although microRNA (miR) was recently shown to be involved in the development of renal fibrosis, few studies have focused on the effects on renal fibrosis of exogenous miR delivered in an in vivo therapeutic setting. The study reported here investigated the effects of miR-146a delivery using polyethylenimine nanoparticles (PEI-NPs) on renal fibrosis in vivo. PEI-NPs bearing miR-146 or control-miR (nitrogen/phosphate ratio: 6) were injected into the tail vein of a mouse model of renal fibrosis induced by unilateral ureteral obstruction. PEI-NPs bearing miR-146 significantly enhanced miR-146a expression in the obstructed kidney compared with the control group, while inhibiting the renal fibrosis area, expression of alpha-smooth muscle actin, and infiltration of F4/80-positive macrophages into the obstructed kidney. In addition, PEI-NPs bearing miR-146a inhibited the transforming growth factor beta 1–Smad and tumor necrosis factor receptor-associated factor 6–nuclear factor kappa B signaling pathways. Control-miR-PEI-NPs did not show any of these effects. These results suggest that the delivery of miR-146a attenuated renal fibrosis by inhibiting pro-fibrotic and inflammatory signaling pathways and that the delivery of appropriate miRs may be a therapeutic option for preventing renal fibrosis in vivo.

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MicroRNA-146a Downregulates NFκB Activity via Targeting TRAF6 and Functions as a Tumor Suppressor Having Strong Prognostic Implications in NK/T Cell Lymphoma

Cited by 164 publications

References 47 publications

Serum Levels of miR-19b and miR-146a as Prognostic Biomarkers for Non-Small Cell Lung Cancer

Serum Levels of miR-19b and miR-146a as Prognostic Biomarkers for Non-Small Cell Lung Cancer

Common polymorphisms of the microRNA genes (miR-146a and miR-196a-2) and gastric cancer risk: an updated meta-analysis

Delivery of microRNA-146a with polyethylenimine nanoparticles inhibits renal fibrosis in vivo

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