miR-889-3p targets SLC35E1 in leprosy: Implications for therapeutic monitoring.

backgroundLeprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae). Despite significant progress in disease control, the molecular mechanisms regulating host responses to M. leprae infection remain incompletely understood. MicroRNAs (miRNAs) are important post-transcriptional regulators that modulate immune responses and host-pathogen interactions in many infectious diseases. However, the specific miRNA-mediated regulatory networks involved in leprosy and their potential implications for monitoring therapeutic responses remain poorly defined.

methodsSkin lesions, serum, and nasal mucosa samples were collected from patients with multibacillary (MB) and paucibacillary (PB) leprosy, as well as from healthy controls. Differentially expressed miRNAs were identified using an Agilent Human miRNA Microarray and validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The interaction between miR-889-3p and its predicted target gene SLC35E1 was examined using dual-luciferase reporter assays. Protein expression of SLC35E1 in skin tissues was evaluated by immunohistochemistry (IHC), and its association with the bacterial index (BI) was analyzed.

resultsMicroarray analysis identified multiple miRNAs with differential expression between leprosy patients and healthy controls across skin lesions, serum, and nasal mucosa samples. Among these candidates, miR-889-3p was consistently upregulated and showed higher expression particularly in multibacillary (MB) patients. qRT-PCR validation confirmed elevated miR-889-3p expression in the serum, skin, and nasal mucosa of MB patients compared with healthy controls, whereas no significant difference was observed in paucibacillary (PB) patients. Notably, miR-889-3p levels decreased significantly after multidrug therapy (MDT) and approached levels observed in healthy controls. Dual-luciferase reporter assays demonstrated that miR-889-3p directly interacts with the 3' untranslated region (3'UTR) of SLC35E1 and significantly increased reporter activity in the wild-type construct, whereas no effect was observed in the mutant construct, supporting a sequence-specific regulatory interaction.Immunohistochemical analysis further revealed increased SLC35E1 expression in leprosy lesions and a strong positive correlation between SLC35E1 expression and the bacteriological index (r = 0.926, p < 0.001).

conclusionThese findings demonstrate that miR-889-3p targets SLC35E1 in leprosy and is associated with bacterial burden and treatment-related changes following multidrug therapy. The dynamic alteration of miR-889-3p expression during therapy suggests that this miRNA may serve as a potential molecular biomarker for monitoring therapeutic response in leprosy. In addition, the identification of the miR-889-3p/SLC35E1 regulatory interaction provides new insights into miRNA-mediated regulatory mechanisms involved in host responses to Mycobacterium leprae infection.