Drug resistance hinders cancer treatment and directly affects cancer outcome and survival rate. While drug resistance is one of the worst features of cancers, there is limited knowledge about its mechanism and initiation in cancers. Noncoding RNAs are one of the most impactful epigenetic elements that are deregulated in many diseases. There is a strong correlation between cancers and noncoding RNAs. In this regard, we tried to find the connection between cancers and this epigenetic factor. In our investigation, we find an axis in which circular RNA, a dominant type of noncoding RNA, could regulate miRNA to control mRNA degradation. We encountered many deregulated pathways and tried to explain the mechanism underlying the CirRNA/miRNA/mRNA axis in drug resistance of cancer, including the most widely recognized resistance type of cancer in the body.
Tumor microenvironment (TME) is a dynamic network that apart from tumor cells includes also cells of the immune system, e.g., neutrophils, which are recruited from blood circulation. In TME, neutrophils are strongly implicated in the direct and indirect interactions with tumor cells or other immune cells, and they play roles in both preventing and/or facilitating tumor progression and metastasis. The dual role of neutrophils is determined by their high plasticity and heterogeneity. Analogous to the macrophages, neutrophils can express antitumoral (N1) and protumoral (N2) phenotypes which differ substantially in morphology and function. N1 phenotype characterizes with a high cytotoxic and proinflammatory activities, while N2 phenotype with immunosuppressive and prometastatic properties. The antitumoral effect of neutrophils includes for example the production of reactive oxygen species or proapoptotic molecules. The protumoral action of neutrophils relies on releasing of proangiogenic and prometastatic mediators, immunosuppressive factors, as well as on direct helping tumor cells in extravasation process. This chapter summarizes the heterogeneity of neutrophils in TME, as well as their dual role on tumor cells.
Microsporidia are poorly understood, ubiquitous eukaryotic parasites that are completely dependent on their hosts for replication. With the discovery of microsporidia species naturally infecting the genetically tractable transparent nematode C. elegans, this host has been used to explore multiple areas of microsporidia biology. Here we review results about microsporidia infections in C. elegans, which began with the discovery of the intestinal-infecting species Nematocida parisii. Recent findings include new species identification in the Nematocida genus, with more intestinal-infecting species, and also a species with broader tissue tropism, the epidermal and muscle-infecting species Nematocida displodere. This species has a longer polar tube infection apparatus, which may enable its wider tissue range. After invasion, multiple Nematocida species appear to fuse host cells, which likely promotes their dissemination within host organs. Localized proteomics identified Nematocida proteins that have direct contact with the C. elegans intestinal cytosol and nucleus, and many of these host-exposed proteins belong to expanded, species-specific gene families. On the host side, forward genetic screens have identified regulators of the Intracellular Pathogen Response (IPR), which is a transcriptional response induced by both microsporidia and the Orsay virus, which is also a natural, obligate intracellular pathogen of the C. elegans intestine. The IPR constitutes a novel immune/stress response that promotes resistance against microsporidia, virus, and heat shock. Overall, the Nematocida/C. elegans system has provided insights about strategies for microsporidia pathogenesis, as well as innate defense pathways against these parasites.
Microsporidia are a large phylum of obligate intracellular parasites that infect an extremely diverse range of animals and protists. In this chapter, we review what is currently known about microsporidia host specificity and what factors influence microsporidia infection. Extensive sampling in nature from related hosts has provided insight into the host range of many microsporidia species. These field studies have been supported by experiments conducted in controlled laboratory environments which have helped to demonstrate host specificity. Together, these approaches have revealed that, while examples of generalist species exist, microsporidia specificity is often narrow, and species typically infect one or several closely related hosts. For microsporidia to successfully infect and complete their life cycle within a compatible host, several steps must occur, including spore germination, host cell invasion, and proliferation of the parasite within the host tissue. Many factors influence infection, including temperature, seasonality, nutrient availability, and the presence or absence of microbes, as well as the developmental stage, sex, and genetics of the host. Several studies have identified host genomic regions that influence resistance to microsporidia, and future work is likely to uncover molecular mechanisms of microsporidia host specificity in more detail.
There has been increased focus on the role of microbial attack as a potential cause of recent declines in the health of the western honey bee, Apis mellifera. The Nosema species, N. apis and N. ceranae, are microsporidian parasites that are pathogenic to honey bees, and infection by these species has been implicated as a key factor in honey bee losses. Honey bees infected with both Nosema spp. display significant changes in their biology at the cellular, tissue, and organismal levels impacting host metabolism, immune function, physiology, and behavior. Infected individuals lead to colony dysfunction and can contribute to colony disease in some circumstances. The means through which parasite growth and tissue pathology in the midgut lead to the dramatic physiological and behavioral changes at the organismal level are only partially understood. In addition, we possess only a limited appreciation of the elements of the host environment that impact pathogen growth and development. Critical for answering these questions is a mechanistic understanding of the host and pathogen machinery responsible for host-pathogen interactions. A number of approaches are already being used to elucidate these mechanisms, and promising new tools may allow for gain- and loss-of-function experiments to accelerate future progress.
