Chi-miR-146a promotes the propagation of Neospora caninum by targeting the TGF-β1/SMAD2 pathway

Neospora caninum is known to induce abortions in various domestic animals (especially cattle and sheep), leading to substantial economic losses in the livestock industry. However, effective strategies for controlling N. caninum infection remains elusive. The precise mechanisms underlying the interaction between N. caninum and its host are not fully elucidated. Our previous study showed an upregulated microRNA (miRNA), Chi-miR-146a, promoted the propagation of N. caninum tachyzoites in caprine endometrial epithelial cells (EECs). The present study investigated its regulatory function during in vitro infection of N. caninum. The expression of Chi-miR-146a was upregulated from 12 h post infection (hpi) to 48 hpi. One of target genes for Chi-miR-146a, tgfb1, was identified and the mRNA and protein levels were downregulated at 24 hpi and 48 hpi. Overexpression of tgfb1 suppressed the propagation of N. caninum tachyzoites in caprine EECs. Further analysis indicated that Chi-miR-146a enhanced in vitro propagation of N. caninum propagation through suppressing the activation of the TGF-β1/SMAD2 signaling pathway. The findings in this study offer a novel theoretical framework for advancing our understanding on mechanisms of intracellular survival of N. caninum and devising preventive strategies against this pathogen.