{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:27:42Z","timestamp":1785414462932,"version":"3.56.0"},"reference-count":45,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32260820"],"award-info":[{"award-number":["32260820"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32560800"],"award-info":[{"award-number":["32560800"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32260820"],"award-info":[{"award-number":["32260820"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["32560800"],"award-info":[{"award-number":["32560800"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009620","name":"Gansu Provincial Department of Education","doi-asserted-by":"publisher","award":["2025CYZC-043"],"award-info":[{"award-number":["2025CYZC-043"]}],"id":[{"id":"10.13039\/501100009620","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007932","name":"Gansu Agricultural University","doi-asserted-by":"publisher","award":["GAU-XKTD-2022-21"],"award-info":[{"award-number":["GAU-XKTD-2022-21"]}],"id":[{"id":"10.13039\/501100007932","id-type":"DOI","asserted-by":"publisher"}]},{"award":["GAU-XKTD-2022-21"],"award-info":[{"award-number":["GAU-XKTD-2022-21"]}],"id":[{"id":"https:\/\/ror.org\/05ym42410","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>The rumen epithelium of Tibetan sheep plays a critical role in energy metabolism and immune defense; however, its post-transcriptional regulatory mechanisms under high-altitude hypoxia stress remain unclear. In this study, we employed integrated mRNA and miRNA transcriptome sequencing to analyze the adaptive strategies of the rumen epithelium in Tibetan sheep at different altitudes. A total of 2183 differentially expressed genes (DEGs) and 135 differentially expressed miRNAs (DEmiRNAs) were identified. Functional enrichment analysis revealed that DEGs and their target genes were significantly enriched in immune-related pathways such as the NF-\u03baB signaling pathway and cytokine\u2013cytokine receptor interaction, as well as metabolic pathways including oxidative phosphorylation and branched-chain amino acid degradation. Integrated network analysis highlighted key regulatory pairs, including oar-miR-370-3p targeting PCK2 and IL1R2, and novel-miR-781 regulating PIK3R5, suggesting coordinated modulation between mitochondrial homeostasis and immune responses. Specifically, the upregulation of immune genes (CCL19, MADCAM1) and heat shock proteins at TS4500m indicates enhanced mucosal immunity and stress tolerance, while altered expression of metabolic genes reflects a shift in energy substrate utilization. These findings elucidate a complex mRNA-miRNA regulatory network that enables Tibetan sheep to maintain rumen epithelial integrity and energy balance under extreme high-altitude conditions, providing novel insights into the molecular basis of hypoxia adaptation in ruminants.<\/jats:p>","DOI":"10.3390\/ani16111650","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T12:09:07Z","timestamp":1779970147000},"page":"1650","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated mRNA-miRNA Transcriptome Analysis Reveals the Molecular Mechanism of Tibetan Sheep Rumen Epithelium Adaptation to High Altitude"],"prefix":"10.3390","volume":"16","author":[{"given":"Lei","family":"Wang","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China"},{"name":"Zhangye Livestock Breeding and Improvement Station, Zhangye 734000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0023-8628","authenticated-orcid":false,"given":"Yuzhu","family":"Sha","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyu","family":"He","sequence":"additional","affiliation":[{"name":"School of Fundamental Sciences, Massey University, Palmerston North 4410, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5348-6781","authenticated-orcid":false,"given":"Pengyang","family":"Shao","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianling","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yapeng","family":"He","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangfeng","family":"Fan","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6057-2551","authenticated-orcid":false,"given":"Xiu","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Du","sequence":"additional","affiliation":[{"name":"Gansu Provincial Animal Husbandry Technology Extension Station, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Liu, X., Sha, Y., Lv, W., Cao, G., Guo, X., Pu, X., Wang, J., Li, S., Hu, J., and Luo, Y. 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