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Pathogens probably modify host miRNAs to facilitate successful infection, so they might be useful targets for vaccination strategies. There are few data on differentially expressed miRNAs in the black-legged tick Ixodes scapularis after infection with Borrelia burgdorferi, the causative agent of Lyme disease in the United States. Small RNA sequencing and qRT-PCR analysis were used to identify and validate differentially expressed I. scapularis salivary miRNAs. Small RNA-seq yielded 133,465,828 (\u226518 nucleotides) and 163,852,135 (\u226518 nucleotides) small RNA reads from Borrelia-infected and uninfected salivary glands for downstream analysis using the miRDeep2 algorithm. As such, 254 miRNAs were identified across all datasets, 25 of which were high confidence and 51 low confidence known miRNAs. Further, 23 miRNAs were differentially expressed in uninfected and infected salivary glands: 11 were upregulated and 12 were downregulated upon pathogen infection. Gene ontology and network analysis of target genes of differentially expressed miRNAs predicted roles in metabolic, cellular, development, cellular component biogenesis, and biological regulation processes. Several Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including sphingolipid metabolism; valine, leucine and isoleucine degradation; lipid transport and metabolism; exosome biogenesis and secretion; and phosphate-containing compound metabolic processes, were predicted as targets of differentially expressed miRNAs. A qRT-PCR assay was utilized to validate the differential expression of miRNAs. This study provides new insights into the miRNAs expressed in I. scapularis salivary glands and paves the way for their functional manipulation to prevent or treat B. burgdorferi infection.<\/jats:p>","DOI":"10.3390\/ijms23105565","type":"journal-article","created":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T13:06:23Z","timestamp":1652706383000},"page":"5565","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Identification of microRNAs in the Lyme Disease Vector Ixodes scapularis"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1963-9926","authenticated-orcid":false,"given":"Deepak","family":"Kumar","sequence":"first","affiliation":[{"name":"Center for Molecular and Cellular Biosciences, University of Southern Mississippi, Hattiesburg, MS 39406, USA"},{"name":"School of Biological, Environmental, and Earth Sciences, University of Southern Mississippi, Hattiesburg, MS 39406, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5951-1011","authenticated-orcid":false,"given":"Latoyia P.","family":"Downs","sequence":"additional","affiliation":[{"name":"School of Biological, Environmental, and Earth Sciences, University of Southern Mississippi, Hattiesburg, MS 39406, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4051-7592","authenticated-orcid":false,"given":"Monica","family":"Embers","sequence":"additional","affiliation":[{"name":"Division of Immunology, Tulane National Primate Research Center, Covington, LA 70433, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex Sutton","family":"Flynt","sequence":"additional","affiliation":[{"name":"Center for Molecular and Cellular Biosciences, University of Southern Mississippi, Hattiesburg, MS 39406, USA"},{"name":"School of Biological, Environmental, and Earth Sciences, University of Southern Mississippi, Hattiesburg, MS 39406, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5596-3304","authenticated-orcid":false,"given":"Shahid","family":"Karim","sequence":"additional","affiliation":[{"name":"Center for Molecular and Cellular Biosciences, University of Southern Mississippi, Hattiesburg, MS 39406, USA"},{"name":"School of Biological, Environmental, and Earth Sciences, University of Southern Mississippi, Hattiesburg, MS 39406, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: Genomics, Biogenesis, Mechanism, and Function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","article-title":"MicroRNAs: Target Recognition and Regulatory Functions","volume":"136","author":"Bartel","year":"2009","journal-title":"Cell."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1126\/science.1085242","article-title":"Role of microRNAs in plant and animal development","volume":"301","author":"Carrington","year":"2003","journal-title":"Science"},{"key":"ref_4","first-page":"D154","article-title":"miRBase: Tools for MicroRNA Genomics","volume":"36","author":"Saini","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1261\/rna.051193.115","article-title":"Two decades of miRNA biology: Lessons and Challenges","volume":"21","author":"Lai","year":"2015","journal-title":"RNA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/nrg1328","article-title":"Micromanagers of gene expression: The Potentially Widespread Influence of Metazoan MicroRNAs","volume":"5","author":"Bartel","year":"2004","journal-title":"Nat. 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