TGF-β–inducible microRNA-183 silences tumor-associated natural killer cells

Donatelli, Sarah S.; Zhou, Junmin; Gilvary, Danielle L.; Eksioglu, Erika A.; Chen, Xianghong; Cress, W. Douglas; Haura, Eric B.; Schabath, Matthew B.; Coppola, Domenico; Wei, Sheng; Djeu, Julie Y.

doi:10.1073/pnas.1319269111

Cited by 186 publications

(146 citation statements)

References 41 publications

(43 reference statements)

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“…Although IL-2 signaling stabilizes the cell-surface expression of activating NKG2D -DAP10 receptor complexes, TGF-b prevents this interaction by inhibiting the expression of DAP10 Sun et al 2012). TGF-b also induces miR-183 expression to repress DAP12 expression, which destabilizes the NKG2D receptors at the surface of NK cells and inhibits their downstream signals (Donatelli et al 2014). …”

Section: Nk Cellsmentioning

confidence: 99%

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

Sanjabi

2017

Cold Spring Harb Perspect Biol

449

306

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Transforming growth factor b (TGF-b) is a pleiotropic cytokine involved in both suppressive and inflammatory immune responses. After 30 years of intense study, we have only begun to elucidate how TGF-b alters immunity under various conditions. Under steady-state conditions, TGF-b regulates thymic T-cell selection and maintains homeostasis of the naïve T-cell pool. TGF-b inhibits cytotoxic T lymphocyte (CTL), Th1-, and Th2-cell differentiation while promoting peripheral ( p)Treg-, Th17-, Th9-, and Tfh-cell generation, and T-cell tissue residence in response to immune challenges. Similarly, TGF-b controls the proliferation, survival, activation, and differentiation of B cells, as well as the development and functions of innate cells, including natural killer (NK) cells, macrophages, dendritic cells, and granulocytes. Collectively, TGF-b plays a pivotal role in maintaining peripheral tolerance against self-and innocuous antigens, such as food, commensal bacteria, and fetal alloantigens, and in controlling immune responses to pathogens.

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Section: Nk Cellsmentioning

confidence: 99%

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

Sanjabi

2017

Cold Spring Harb Perspect Biol

449

306

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“…Otherwise, deregulation of the TGFB1 signaling pathway may be induced by oscillating miRNA levels, such as miR-183. Therefore, the use of therapeutic agents that facilitate the TGFB1 signaling pathway and silence the expression of miR-183 may represent a promising strategy for activating the immune system in lung therapy (62). These types of approach result in decreased activation of TGFB1 and the SMAD-dependent TGFB1 signaling pathway, and inhibit ROS production.…”

Section: Preclinical and Clinical Strategies For Targeting The Tgfb1 mentioning

confidence: 99%

Advances in targeting the transforming growth factor β1 signaling pathway in lung cancer radiotherapy (Review)

Tang

Luo

et al. 2017

Oncol Lett

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Abstract. Lung cancer was demonstrated to be the most lethal type of malignant tumor amongst humans in the global cancer statistics of 2012. As one of the primary treatments, radiotherapy has been reported to induce remission in, and even cure, patients with lung cancer. However, the side effects of radiotherapy may prove lethal in certain patients. In past decades, the transforming growth factor β1 (TGFB1) signaling pathway has been revealed to serve multiple functions in the control of lung cancer progression and the radiotherapy response. In mammals, this signaling pathway is initiated through activation of the TGFB1 receptor complex, which signals via cytoplasmic SMAD proteins or other downstream signaling pathways. Multiple studies have demonstrated that TGFB1 serves important functions in lung cancer radiotherapy. The present study summarized and reviewed recent progress in elucidating the function of the TGFB1 signaling pathway in predicting radiation pneumonitis, as well as current strategies for targeting the TGFB1 signaling pathway in lung cancer radiotherapy, which may provide potential targets for lung cancer therapy.

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“…In contrast, tumorsecreted miRNA-214 induces Treg. Regarding NK cells, the TGF-β-inducible miRNA-183 affects NK cell activity [130]. Thus, the regulation of miRNAs within the cancer cell alters the TME through manipulation.…”

Section: Role Of Mirnas In Immune Cell Functionmentioning

confidence: 99%

The Role of Immune Modulatory MicroRNAs in Tumors

Seliger¹,

Meinhardt²,

Falke³

2016

RNA Interference

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Tumors could evade the control of CD8 + T and/or NK cell-mediated surveillance by distinct immune escape strategies. These include the aberrant expression of HLA class I antigens, coinhibitory or costimulatory molecules, and components of the interferon (IFN) signal transduction pathway. In addition, alterations of the tumor microenvironment could interfere with a proper antitumoral immune response by downregulating or inhibiting the frequency and/or activity of immune effector cells and professional antigen presenting cells. Based on the identification as major mediators of the posttranscriptional silencing of gene expression, microRNAs (miRNAs) have been suggested to play a key role in many biological processes known to be involved in neoplastic transformation. Indeed, miRNA expression is frequently deregulated in many cancer types and could have tumor-suppressive as well as oncogenic potential. This review focused on the characterization of miRNAs, which are involved in the control of the immune surveillance or immune escape of tumors and their use as potential diagnostic and prognostic biomarkers as well as therapeutic targets. Moreover, miRNAs can have dual activities by affecting the neoplastic and immunogenic phenotype of tumors.

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TGF-β–inducible microRNA-183 silences tumor-associated natural killer cells

Cited by 186 publications

References 41 publications

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

Advances in targeting the transforming growth factor β1 signaling pathway in lung cancer radiotherapy (Review)

The Role of Immune Modulatory MicroRNAs in Tumors

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