Role of microRNAs in the immune system, inflammation and cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Raisch J
PROVIDER: S-EPMC3662938 | biostudies-literature | 2013 May
REPOSITORIES: biostudies-literature
Publications
Role of microRNAs in the immune system, inflammation and cancer.
Raisch Jennifer J Darfeuille-Michaud Arlette A Nguyen Hang Thi Thu HT
World journal of gastroenterology 20130501 20
MicroRNAs, a key class of gene expression regulators, have emerged as crucial players in various biological processes such as cellular proliferation and differentiation, development and apoptosis. In addition, microRNAs are coming to light as crucial regulators of innate and adaptive immune responses, and their abnormal expression and/or function in the immune system have been linked to multiple human diseases including inflammatory disorders, such as inflammatory bowel disease, and cancers. In ...[more]
Similar Datasets
Project description:During malignant transformation, accumulated somatic mutations endow cancer cells with increased invasiveness and immunogenicity. Under selective pressure, these highly immunogenic cancer cells develop multiple strategies to evade immune attack. It has been well established that cancer cells could downregulate the expression of major histocompatibility complex, acquire alterations in interferon pathway, and upregulate the activities of immune checkpoint pathways. Besides, cancer cells secret numerous cytokines, exosomes, and microvesicles to regulate the functions and abundances of components in the tumor microenvironment including immune effector cells and professional antigen presentation cells. As the vital determinant of post-transcriptional regulation, microRNAs (miRNAs) not only participate in cancer initiation and progression but also regulate anti-cancer immune response. For instance, some miRNAs affect cancer immune surveillance and immune escape by interfering the expression of immune attack-associated molecules. A growing body of evidence indicated that cancer-derived immune modulatory miRNAs might be promising targets to counteract cancer immune escape. In this review, we summarized the role of some miRNAs in cancer immune escape and discussed their potential clinical application as treatment targets.
| S-EPMC7103070 | biostudies-literature
Project description:During different stages of tumor development the immune system can either identify and destroy tumors, or promote their growth. Therapies targeting the immune system have emerged as a promising treatment modality for breast cancer, and immunotherapeutic strategies are being examined in preclinical and clinical models. However, our understanding of the complex interplay between cells of the immune system and breast cancer cells is incomplete. In this article, we review recent findings showing how the immune system plays dual host-protective and tumor-promoting roles in breast cancer initiation and progression. We then discuss estrogen receptor ? (ER?)-dependent and ER?-independent mechanisms that shield breast cancers from immunosurveillance and enable breast cancer cells to evade immune cell induced apoptosis and produce an immunosuppressive tumor microenvironment. Finally, we discuss protumorigenic inflammation that is induced during tumor progression and therapy, and how inflammation promotes more aggressive phenotypes in ER? positive breast cancers.
| S-EPMC4919022 | biostudies-literature
Project description:Major depression during pregnancy is a common psychiatric disorder that arises from a complex and multifactorial etiology. Psychosocial stress, sex, hormones, and genetic vulnerability increase the risk for triggering mood disorders. Microglia and toll-like receptor 4 play a crucial role in triggering wide and varied stress-induced responses mediated through activation of the inflammasome; this leads to the secretion of inflammatory cytokines, increased serotonin metabolism, and reduction of neurotransmitter availability along with hypothalamic-pituitary-adrenal axis hyperactivity. Dysregulation of this intricate neuroimmune communication network during pregnancy modifies the maternal milieu, enhancing the emergence of depressive symptoms and negative obstetric and neuropsychiatric outcomes. Although several studies have clearly demonstrated the role of the innate immune system in major depression, it is still unclear how the placenta, the brain, and the monoaminergic and neuroendocrine systems interact during perinatal depression. Thus, in the present review we describe the cellular and molecular interactions between these systems in major depression during pregnancy, proposing that the same stress-related mechanisms involved in the activation of the NLRP3 inflammasome in microglia and peripheral myeloid cells in depressed patients operate in a similar fashion in the neuroimmune placenta during perinatal depression. Thus, activation of Toll-like receptor 2 and 4 signaling and the NLRP3 inflammasome in placental immune cells may promote a shift of the Th1/Th2 bias towards a predominant Th1/Th17 inflammatory response, associated with increased secretion of pro-inflammatory cytokines, among other secreted autocrine and paracrine mediators, which play a crucial role in triggering and/or exacerbating depressive symptoms during pregnancy.
| S-EPMC5563787 | biostudies-other
Project description:Cervical cancer (CC) is the fourth most common cause of cancer death in women. The most important risk factor for the development of CC is cervical infection with human papilloma virus (HPV). Inflammation is a protective strategy that is triggered by the host against pathogens such as viral infections that acts rapidly to activate the innate immune response. Inflammation is beneficial if it is brief and well controlled; however, if the inflammation is excessive or it becomes of chronic duration, it can produce detrimental effects. HPV proteins are involved, both directly and indirectly, in the development of chronic inflammation, which is a causal factor in the development of CC. However, other factors may also have a potential role in stimulating chronic inflammation. MicroRNAs (miRNAs) (a class of noncoding RNAs) are strong regulators of gene expression. They have emerged as key players in several biological processes, including inflammatory pathways. Abnormal expression of miRNAs may be linked to the induction of inflammation that occurs in CC. Exosomes are a subset of extracellular vesicles shed by almost all types of cells, which can function as cargo transfer vehicles. Exosomes contain proteins and genetic material (including miRNAs) derived from their parent cells and can potentially affect recipient cells. Exosomes have recently been recognized to be involved in inflammatory processes and can also affect the immune response. In this review, we discuss the role of HPV proteins, miRNAs and exosomes in the inflammation associated with CC.
| S-EPMC6999596 | biostudies-literature
Project description:Breast cancer (BC) is the most common type of cancer in women worldwide, and despite advances in treatments, its incidence and mortality are increasing. Therefore, it is necessary to develop new, non-invasive tests that provide more accurate diagnosis and prognosis in a timely manner. A promising approach is measuring the presence of biomarkers to detect tumors at various stages and determine their specific characteristics, thus allowing for more personalized treatment. MicroRNAs (miRNAs) serve a role in gene expression, primarily by interacting with messenger RNAs, and may be potential biomarkers for detecting cancer. They are detectable in tissues and blood, including plasma and/or serum, are stable and often tumor specific. Also, different miRNAs are associated with specific BC molecular subtypes. Triple-negative BC (TNBC) is a type of BC in which the primary targets for hormonal therapy are absent. It is an aggressive phenotype, which frequently metastasizes and is associated with an unfavorable prognosis. The present review focuses on circulating miRNAs in patients with TNBC, with an emphasis on their interaction with the immune response checkpoint genes PD-1, PD-L1 and CTLA4. Modulation and response of the immune system are of interest in cancer treatment due to the success of immunotherapy in the treatment of various neoplasms. Based on the findings of this literature review and the in silico analysis performed as part of this review, it is concluded that circulating hsa-miR-195 and hsa-miR-155 in TNBC interact with checkpoint genes involved in the immune response. Further analysis of the expression of these circulating miRNAs and their association with prognosis in patients with TNBC treated with immunotherapy should be assessed to evaluate their possible use as non-invasive predictive biomarkers. In addition, functional studies to analyze biologically relevant targets in the development and prognosis of TNBC, which could be therapeutic targets, are also recommended.
| S-EPMC7499949 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-05-07 | E-GEOD-60832 | biostudies-arrayexpress
Project description:Current hypothesis suggests that genetic, immunological, and bacterial factors contribute essentially to the pathogenesis of inflammatory bowel disease. Variations within the gene loci encoding protein tyrosine phosphatases (PTPs) have been associated with the onset of inflammatory bowel disease. PTPs modulate the activity of their substrates by dephosphorylation of tyrosine residues and are critical for the regulation of fundamental cellular signaling processes. Evidence emerges that expression levels of PTPN2, PTPN11, and PTPN22 are altered in actively inflamed intestinal tissue. PTPN2 seems to be critical for protecting intestinal epithelial barrier function, regulating innate and adaptive immune responses and finally for maintaining intestinal homeostasis. These observations have been confirmed in PTPN2 knockout mice in vivo. Those animals are clearly more susceptible to intestinal and systemic inflammation and feature alterations in innate and adaptive immune responses. PTPN22 controls inflammatory signaling in lymphocytes and mononuclear cells resulting in aberrant cytokine secretion pattern and autophagosome formation. PTPN22 deficiency in vivo results in more severe colitis demonstrating the relevance of PTPN22 for intestinal homeostasis in vivo. Of note, loss of PTPN22 promotes mitogen-activated protein kinase-induced cytokine secretion but limits secretion of nuclear factor ?B-associated cytokines and autophagy in mononuclear cells. Loss of PTPN11 is also associated with increased colitis severity in vivo. In summary, dysfunction of those PTPs results in aberrant and uncontrolled immune responses that result in chronic inflammatory conditions. This way, it becomes more and more evident that dysfunction of PTPs displays an important factor in the pathogenesis of chronic intestinal inflammation, in particular inflammatory bowel disease.
| S-EPMC4329025 | biostudies-literature
Project description:Pancreatic cancer (PC) is the 5th leading cause of cancer related death in the developed world with more than 260,000 deaths annually worldwide and with a dismal 5-year survival. Surgery is the only potential hope of cure for PC, but, unfortunately, only 20% PC patients is resectable at the time of diagnosis. Therapeutic research efforts have mainly focused on improvements in radio/ chemo treatments and to date, there are only a few chemotherapeutic agents that have shown to be effective against PC, including gemcitabine with or without abraxane as well as a combination of 5-FU, leucovorin, oxaliplatin and irinotecan (the so-called FOLFIRINOX regimen). The survival of patients treated with these regimens is marginal and hence we are in urgent need of novel therapeutic approaches to treat pancreatic cancer. The success of immunotherapeutic strategies in other cancers and various evidences that pancreatic adenocarcinoma elicits antitumor immune responses, suggest that immunotherapies can be a promising alternative treatment modality for this deadly disease. PC immunotherapy treatments include passive immunotherapeutic approaches, such as the use of effector cells generated in vitro, and active immunotherapeutic strategies, which goal is to stimulate an antitumor response in vivo, by means of vaccination. In this review, we describe the immune suppressive mechanisms of pancreatic cancer and discuss recent preclinical and clinical efforts toward PC immunotherapy, including passive approaches, such as the use of antibodies and active strategies (vaccination), with a special mention of most recent treatment with CRS-207 and GVAX.
| S-EPMC4514060 | biostudies-other
Project description:In recent years there has been an increasing interest of the scientific community on exosome research, with particular emphasis on the mechanisms by which tumor-derived exosomes can promote tumor growth. Particularly, exosome-mediated immune-escape is under deep investigation and still represents a quite controversial issue. Tumor-derived exosomes are carriers of information able to reprogram functions of immune target cells, influencing their development, maturation, and antitumor activities. They deliver proteins similar to those of the parent cancer cells, but also genetic messages like genomic DNA, mRNA, and microRNAs (miRNAs) that ultimately share the so called "tumor microenvironment" in a pro-tumoral fashion. The content of tumor-derived exosomes could be implicated in several signaling pathways operating in the tumor microenvironment, providing a further modality of dys-regulation of antitumor immunity. The aim of this review is to provide a state-of-the-art highlight of to the most recent discoveries in the field of interaction between tumor-derived exosomic miRNAs and the cells of immune system.
| S-EPMC5466544 | biostudies-literature
Project description:Post-partum uterine inflammation (endometritis) is associated with lower fertility at both the time of infection and after the inflammation has resolved. It was hypothesized that aberrant DNA methylation may be involved in the sub-fertility associated with post-partum uterine inflammation. The objective of this study was to characterize genome-wide DNA methylation and gene expression in the endometrium of dairy cows with sub-clinical endometritis. Endometrial tissues were obtained at 29 days post-partum (n=12) and Agilent two-colour microarrays were used to characterize transcription and DNA methylation profiles. Analyses revealed 1,856 probes to be differentially expressed in animals with subclinical endometritis (SUI, n=6) compared with control cows (NUI, n=6, P<0.05, Storey Multiple testing correction). No significant associations among DNA methylation and gene expression were detected. Further analysis of gene expression data using GeneGo Metacore and Gene Set Enrichment Analysis identified several pathways and processes enriched in the comparison. Several pathways that are involved in the innate immune response were enriched in SUI cows. Consistent with the presence of microorganisms in the uterus, there was enrichment for the Toll-like receptor (TLR) signaling pathway, including increased expression of the transcription factor NFKB1, the pro-inflammatory cytokines IL1A and IL1B, downstream chemokines, cytokines, and acute phase and antimicrobial proteins in the endometrium of SUI cows. Furthermore, the chemokine signaling pathway was enriched in SUI cows, with increased expression of genes that attract cells of the innate immune system. Increased expression of IL-8 and CXCL6, chemotactic factors for recruitment of neutrophils along with the immune cell surface marker PTPRC in SUI cows is consistent with the greater number of polymorphonuclear cells present in the uterus of these cows. Several antimicrobial peptides (LAP, TAP, DEFB1, DEFB10, DEFB103B, DEFB7) and acute phase proteins, including SAA3, LBP, and the complement gene CFB, had greater expression in SUI cows. Gene expression profiles in cows with subclinical endometritis in this study indicate that the immune response is activated, potentially resulting in a local pro-inflammatory environment in the uterus. If this period of inflammation is prolonged, it could result in tissue damage or failure to complete involution of the uterus, which may create a sub-optimal environment for future pregnancy. 12 animals were enrolled in this study, 2 samples from each animal were used for microarray analysis consisting of caruncular and intercaruncular endometrium. A reference design was used for hybridisation, whereby each of the 24 samples were hybridised to individual microarrays along with a pooled reference sample. The reference sample was generated by taking equal concentrations of each of the experimental samples.
2015-05-07 | E-GEOD-58794 | biostudies-arrayexpress