Abstract
BackgroundCryptosporidium is an important zoonotic pathogen responsible for severe enteric diseases in humans and animals. However, the molecular mechanisms underlying host and Cryptosporidium interactions are still not clear.MethodsTo study the roles of circRNAs in host cells during Cryptosporidium infection, the expression profiles of circRNAs in HCT-8 cells infected with C. parvum were investigated using a microarray assay, and the regulatory role of a significantly upregulated circRNA, ciRS-7, was investigated during C. parvum infection.ResultsC. parvum infection caused notable alterations in the expression profiles of circRNAs in HCT-8 cells, and a total of 178 (including 128 up- and 50 downregulated) circRNAs were significantly differentially expressed following C. parvum infection. Among them, ciRS-7 was significantly upregulated and regulated the NF-κB signaling pathway by sponging miR-1270 during C. parvum infection. Furthermore, the ciRS-7/miR-1270/relA axis markedly affected the propagation of C. parvum in HCT-8 cells.ConclusionsOur results revealed that ciRS-7 would promote C. parvum propagation by regulating the miR-1270/relA axis and affecting the NF-κB pathway. To the best of our knowledge, this is the first study to investigate the role of circRNA during Cryptosporidium infection, and the findings provide a novel view for implementing control strategies against Cryptosporidium infection.Graphical
Highlights
Cryptosporidium is an important zoonotic pathogen responsible for severe enteric diseases in humans and animals
The expression of ciRS‐7 was induced by C. parvum infection in HCT‐8 cells Among 128 significantly upregulated circular RNA (circRNA), a previously well-studied circRNA, hsa_circ_0001946_CBC1, was remarkably upregulated by nearly eightfold following C. parvum infection for 24 h in microarray analysis (Additional file 3: Table S3). Quantita‐ tive real-time polymerase chain reaction (qRT-PCR) confirmed the microarray results and found continuously increased expression of ciRS-7 in HCT-8 cells from 12-h post-infection to 48 hpi (Fig. 2a), suggesting the potential role of this circRNA during C. parvum infection
CiRS‐7 acted as a sponge of miR‐1270 in HCT‐8 cells following C. parvum infection Considering the involvement of ciRS-7 in many physiological or pathological processes via binding to specific miRNAs [22,23,24], we predicted 22 potential miRNA targets of ciRS-7 by using starBase v2.0 [25]
Summary
Cryptosporidium is an important zoonotic pathogen responsible for severe enteric diseases in humans and animals. The serious consequences of cryptosporidiosis are underestimated and underreported owing to commonly asymptomatic carriage in immunocompetent hosts, insufficient attention, and the unavailability of perfect diagnostic procedures for this important disease worldwide. Only one drug, nitazoxanide, has been proven to treat cryptosporidiosis [7] This drug is only 56–96% effective in immunocompetent hosts, and no efficacy is found in immune-compromised individuals, especially in patients with advanced AIDS [7]. Considering that the severity of cryptosporidiosis is closely associated with host status, especially immunity [7, 8], thoroughly understanding the interaction between hosts and Cryptosporidium is essential to develop effectively well-directed control strategies against cryptosporidiosis
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