microRNAs are ligands of Toll-like receptors

Chen, Xi; Liang, Hongwei; Zhang, Junfeng; Zen, Ke; Zhang, Chenyu

doi:10.1261/rna.036319.112

Cited by 76 publications

(65 citation statements)

References 10 publications

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“…miR-21 and miR-29a can bind to TLR 7 and TLR 8 as agonists, leading to NF-κB signaling activation and secretion of IL-6 and TNF-α, which locally promote cancer cell growth and metastasis when treating cancer, and may cause systemic immune toxicity [74]. miRNAs may bind to the TLR 7 and TLR 8 via the GU-rich motif (GUUG for miR-21 and GGUU for miR-29a), which is crucial for RNA–TLR recognition [75,76]. …”

Section: Current Challenges In Mirna Deliverymentioning

confidence: 99%

In vivo delivery of miRNAs for cancer therapy: Challenges and strategies

Chen

Gao

Huang

2015

Advanced Drug Delivery Reviews

570

497

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MicroRNAs (miRNAs), small non-coding RNAs, can regulate post-transcriptional gene expressions and silence a broad set of target genes. miRNAs, aberrantly expressed in cancer cells, play an important role in modulating gene expressions, thereby regulating downstream signaling pathways and affecting cancer formation and progression. Oncogenes or tumor suppressor genes regulated by miRNAs mediate cell cycle progression, metabolism, cell death, angiogenesis, metastasis and immunosuppression in cancer. Recently, miRNAs have emerged as therapeutic targets or tools and biomarkers for diagnosis and therapy monitoring in cancer. Since miRNAs can regulate multiple cancer-related genes simultaneously, using miRNAs as a therapeutic approach plays an important role in cancer therapy. However, one of the major challenges of miRNA-based cancer therapy is to achieve specific, efficient and safe systemic delivery of therapeutic miRNAs In vivo. This review discusses the key challenges to the development of the carriers for miRNA-based therapy and explores current strategies to systemically deliver miRNAs to cancer without induction of toxicity.

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Section: Current Challenges In Mirna Deliverymentioning

confidence: 99%

In vivo delivery of miRNAs for cancer therapy: Challenges and strategies

Chen

Gao

Huang

2015

Advanced Drug Delivery Reviews

570

497

View full text Add to dashboard Cite

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“…Fragments of the viral genome, as well as virus-encoded small RNAs, such as those encoded by EBV, and certain host cell miRNAs, have been shown to trigger target cell PRRs. Although triggering of the PRR system results in complex responses, in some cases it may induce an increased activation status of these cells (37)(38)(39). Most of the described EV-mediated effects on the function of other cells are restricted to in vitro systems or occur within the same organism.…”

Section: "Mister Postman": What Do Evs and Viruses Delivermentioning

confidence: 99%

Extracellular vesicles and viruses: Are they close relatives?

Hoen

Cremer

Gallo

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

414

390

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Extracellular vesicles (EVs) released by various cells are small phospholipid membrane-enclosed entities that can carry miRNA. They are now central to research in many fields of biology because they seem to constitute a new system of cell–cell communication. Physical and chemical characteristics of many EVs, as well as their biogenesis pathways, resemble those of retroviruses. Moreover, EVs generated by virus-infected cells can incorporate viral proteins and fragments of viral RNA, being thus indistinguishable from defective (noninfectious) retroviruses. EVs, depending on the proteins and genetic material incorporated in them, play a significant role in viral infection, both facilitating and suppressing it. Deciphering the mechanisms of EV-cell interactions may facilitate the design of EVs that inhibit viral infection and can be used as vehicles for targeted drug delivery.

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“…Exogenous factors may alter the function of this TLR leading to a defect of the innate immunity response. In this regard, it has been demonstrated that heat-shock proteins (49) and microRNAs (50) are ligands for TLR7 and that exogenous factors, in particular UV radiations, may deregulate their expression (51,52). As a consequence, under certain circumstances the TLR7 expression can be downregulated, diminishing its activity toward innate and acquired immunity, and consequently, also toward the control of UV-induced skin cancers.…”

Section: Discussionmentioning

confidence: 99%

Association between Toll-like receptor 7 Gln11Leu single-nucleotide polymorphism and basal cell carcinoma

et al. 2016

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Abstract. Non-melanoma skin cancers (NMSC) are the most common form of human skin cancer. The majority of NMSC are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with a BCC:SCC incidence ratio of 4:1 in immunocompetent patients. Toll-like receptors (TLRs) are transmembrane glycoproteins that recognize pathogen-associated molecular patterns and damage-associated molecular patterns, against which they activate the innate immune response and initiate the adaptive immune response. Genetic variations of these receptors can alter the immune system and are involved in evolution and susceptibility of various diseases, including cancer. Imiquimod, an agonist of TLR7, is applied topically in the treatment of premalignant and malignant skin disorders, in particular BCC. The high efficacy of this TLR7 agonist toward BCC supports a possible role of this receptor in the induction of BCC and, consequently, polymorphisms of this receptor could be responsible for a greater or lesser susceptibility to BCC. The aim of the present study was to evaluate whether the presence of the functional TLR7 rs179008/Gln11Leu promoter polymorphism conferred an increased susceptibility to BCC. A case-control study with 177 BCC cases and 158 controls was performed to highlight the possible association between this polymorphism and the susceptibility to BCC. As the TLR7 gene is localized on chromosome X, the allelic frequency of this polymorphism was analyzed separately in males and females. The analysis of the distribution of frequencies of wild-type TLR7 and variant TLR7 carrying the single-nucleotide polymorphism (SNP) rs179008 in patients with BCC and healthy subjects did not reveal any statistically significant difference between cases and controls. This study does not suggest the involvement of the SNP rs179008 of TLR7 in the susceptibility to BCC, but cannot exclude a role for TLR7 in BCC carcinogenesis considering the high efficacy of the TLR7 agonist, imiquimod, in the treatment of this neoplastic disorder.

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microRNAs are ligands of Toll-like receptors

Cited by 76 publications

References 10 publications

In vivo delivery of miRNAs for cancer therapy: Challenges and strategies

In vivo delivery of miRNAs for cancer therapy: Challenges and strategies

Extracellular vesicles and viruses: Are they close relatives?

Association between Toll-like receptor 7 Gln11Leu single-nucleotide polymorphism and basal cell carcinoma

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