Quantitative Proteomics Reveals that miR-155 Regulates the PI3K-AKT Pathway in Diffuse Large B-Cell Lymphoma

Huang, Xin; Shen, Yulei; Liu, Miao; Bi, Chengfeng; Jiang, Chunsun; Iqbal, Javeed; McKeithan, Timothy W.; Chan, Wing C.; Ding, Shilei; Fu, Kai

doi:10.1016/j.ajpath.2012.03.013

Cited by 112 publications

(105 citation statements)

References 35 publications

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“…The PI3K/Akt pathway plays an important role in the regulation of TJ assembly and integrity (González-Mariscal et al, 2008). At the same time, Akt signaling is activated by overexpressed miR-155 and downregulated after miR-155 inhibition (Yamanaka et al, 2009;Huang et al, 2012). In agreement with these previous studies, Akt phosphorylation levels (both at Thr308 and Ser473) were Ͼ3-fold lower in the Inhibitor samples compared with Controls (Fig.…”

Section: Downregulation Of Mir-155 Results In Increased Expression Ofsupporting

confidence: 80%

“…A negative regulation of ZO-1 expression by miR-155 has been demonstrated previously (Tian et al, 2013); however, its exact mechanism is unclear. Based on our analysis, we speculate that ZO-1 stability is mediated via a decrease of Akt activity and induced by miR-155 downregulation, which was also demonstrated by others (Yamanaka et al, 2009;Huang et al, 2012). Our results indicate that Akt phosphorylation could be induced by the upregulation of a direct miR-155 target protein, Rheb, which can supress Akt phosphorylation via an S6K-insulin receptor substrate protein-Akt feedback loop (Di et al, 2012;Cao et al, 2013).…”

Section: Discussionmentioning

confidence: 72%

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In Vivo Inhibition of miR-155 Promotes Recovery after Experimental Mouse Stroke

Caballero-Garrido

Peña-Philippides

Lordkipanidze

et al. 2015

Journal of Neuroscience

159

132

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A multifunctional microRNA, miR-155, has been recently recognized as an important modulator of numerous biological processes. In our previous in vitro studies, miR-155 was identified as a potential regulator of the endothelial morphogenesis. The present study demonstrates that in vivo inhibition of miR-155 supports cerebral vasculature after experimental stroke. Intravenous injections of a specific miR-155 inhibitor were initiated at 48 h after mouse distal middle cerebral artery occlusion (dMCAO). Microvasculature in peri-infarct area, infarct size, and animal functional recovery were assessed at 1, 2, and 3 weeks after dMCAO. Using in vivo two-photon microscopy, we detected improved blood flow and microvascular integrity in the peri-infarct area of miR-155 inhibitor-injected mice. Electron microscopy revealed that, in contrast to the control group, these animals demonstrated well preserved capillary tight junctions (TJs). Western blot analysis data indicate that improved TJ integrity in the inhibitor-injected animals could be associated with stabilization of the TJ protein ZO-1 and mediated by the miR-155 target protein Rheb. MRI analysis showed significant (34%) reduction of infarct size in miR-155 inhibitor-injected animals at 21 d after dMCAO. Reduced brain injury was confirmed by electron microscopy demonstrating decreased neuronal damage in the peri-infarct area of stroke. Preservation of brain tissue was reflected in efficient functional recovery of inhibitor-injected animals. Based on our findings, we propose that in vivo miR-155 inhibition after ischemia supports brain microvasculature, reduces brain tissue damage, and improves the animal functional recovery.

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Section: Downregulation Of Mir-155 Results In Increased Expression Ofsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 72%

In Vivo Inhibition of miR-155 Promotes Recovery after Experimental Mouse Stroke

Caballero-Garrido

Peña-Philippides

Lordkipanidze

et al. 2015

Journal of Neuroscience

159

132

View full text Add to dashboard Cite

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“…One signaling pathway that is targeted at multiple levels by mir-155 (15,25,26), and could reasonably account for the defect observed, is the PI3K/Akt signaling cascade. We isolated CD8 + T cells from WT and 155KO mice and stimulated them with anti-CD3 for 30 min in vitro.…”

Section: Mir-155 Promotes T Cell Survival Via Aktmentioning

confidence: 99%

Micro-RNA 155 Is Required for Optimal CD8+ T Cell Responses to Acute Viral and Intracellular Bacterial Challenges

Lind

Elford

Ohashi

2013

The Journal of Immunology

107

116

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Recent studies have begun to define the role of micro-RNAs in regulating the immune response. Micro-RNA155 (mir-155) has been shown to play a role in germinal center formation, T cell inflammation, and regulatory T cell development. In this study, we evaluated the role of mir-155 in cytotoxic T cell function. We report in this study that mice lacking mir-155 have impaired CD8+ T cell responses to infections with lymphocytic choriomeningitis virus and the intracellular bacteria Listeria monocytogenes. We show by a series of adoptive transfer studies that the impaired CD8+ T cell response to L. monocytogenes is T cell intrinsic. In addition, we observed that CD8+ T cells lacking mir-155 have impaired activation of the prosurvival Akt pathway after TCR cross-linking. These data suggest that mir-155 may be a good target for therapies aimed at modulating immune responses.

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“…In addition, miR-155 suppresses the in vitro growth-inhibitory effects of TGF-β1 and BMP2/4 in DLBCL cells by SMAD5 downregulation, 59 and it controls PI3K-AKT pathway activity by PIK3R1 targeting. 60 Furthermore, overexpression of this miRNA promotes TNFα-dependent proliferation of DLBCL cells in vivo in xenotransplanted mice. 56 Recently, it has been demonstrated that SHIP1 is differentially expressed between the two molecular subtypes of DLBCL, GC B-cell-like, and activated B-cell-like (ABC) DLBCL.…”

Section: Aberrant Expression Of Mirnas In B-cell Lymphomas and Their mentioning

confidence: 99%

MicroRNAs as B-cell lymphoma biomarkers

Manterola¹,

Fernández-Mercado²,

Larrea³

et al. 2015

BLCTT

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B-cell lymphomas represent a group of more than 35 recognized mature B-cell neoplasms differentiated largely on the basis of immunohistochemical staining patterns that are often challenging to accurately diagnose. Despite having been only formally recognized just over 10 years ago, microRNAs (miRNAs) have become one of the trendiest topics in biology. Dysregulation of miRNAs is a ubiquitous feature of cancer in general, including B-cell lymphomas. Many of the miRNAs aberrantly expressed in B-cell lymphomas also play a crucial regulatory role in normal hematopoietic function. MiRNAs show great potential as novel biomarkers of cancer, as they can differentiate cancers according to diagnosis and developmental stage, even discriminating between cancers that are poorly separated histologically. Furthermore, they can be robustly measured from routinely prepared formalin-fixed paraffin-embedded biopsy material and biological fluids such as blood. Here, we consider the identity, function, and biomarker potential of miRNAs in B-cell lymphomas and, most importantly, the hurdles that remain to be overcome if they are really to become part of future clinical practice.

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Quantitative Proteomics Reveals that miR-155 Regulates the PI3K-AKT Pathway in Diffuse Large B-Cell Lymphoma

Cited by 112 publications

References 35 publications

In Vivo Inhibition of miR-155 Promotes Recovery after Experimental Mouse Stroke

In Vivo Inhibition of miR-155 Promotes Recovery after Experimental Mouse Stroke

Micro-RNA 155 Is Required for Optimal CD8+ T Cell Responses to Acute Viral and Intracellular Bacterial Challenges

MicroRNAs as B-cell lymphoma biomarkers

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