{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:49:35Z","timestamp":1760057375516,"version":"build-2065373602"},"reference-count":68,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["32072687","32302712","A120202"],"award-info":[{"award-number":["32072687","32302712","A120202"]}]},{"name":"Agricultural Germplasm Resources Survey, Collection, Protection, and Identification Service Project of the Ministry of Agriculture and Rural Affairs","award":["32072687","32302712","A120202"],"award-info":[{"award-number":["32072687","32302712","A120202"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neonatal mammals must rapidly adapt to significant physiological changes during the transition from the intrauterine to extrauterine environments. This adaptation, particularly in the metabolic and respiratory systems, is essential for survival. MicroRNAs (miRNAs) are small noncoding RNAs that regulate various physiological and pathological processes by binding to the 3\u2032 untranslated regions of mRNAs. This study aimed to identify miRNAs involved in the early extrauterine adaptation of neonatal piglets and explore their functions. We performed small RNA sequencing on six tissues (heart, liver, spleen, lung, multifidus muscle, and duodenum) from piglets 24 h before birth (day 113 of gestation) and 6 h after birth. A total of 971 miRNA precursors and 1511 mature miRNAs were identified. Tissue-specific expression analysis revealed 881 tissue-specific miRNAs and 164 differentially expressed miRNAs (DE miRNAs) across the tissues. Functional enrichment analysis showed that these DE miRNAs are significantly enriched in pathways related to early extrauterine adaptation, such as the NF\u03baB, PI3K\/AKT, and Hippo pathways. Specifically, miR-22-3p was significantly upregulated in the liver post-birth and may regulate the PI3K\/AKT pathway by targeting AKT3, promoting gluconeogenesis, and maintaining glucose homeostasis. Dual-luciferase reporter assays and HepG2 cell experiments confirmed AKT3 as a target of miR-22-3p, which activates the AKT\/FoxO1 pathway, enhancing gluconeogenesis and glucose production. Furthermore, changes in blood glucose and liver glycogen levels in newborn piglets further support the role of miR-22-3p in glucose homeostasis. This study highlights the importance of miRNAs, particularly miR-22-3p, in the early extrauterine adaptation of neonatal piglets, offering new insights into the physiological adaptation of neonatal mammals.<\/jats:p>","DOI":"10.3390\/ijms26031316","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T05:55:22Z","timestamp":1738648522000},"page":"1316","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification and Functional Analysis of Key microRNAs in the Early Extrauterine Environmental Adaptation of Piglets"],"prefix":"10.3390","volume":"26","author":[{"given":"Mingxing","family":"Wen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanling","family":"Qiu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Chongqing Academy of Animal Sciences, Chongqing 402460, China"},{"name":"Key Laboratory of Pig Industry Sciences, Ministry of Agriculture, Chongqing 402460, China"},{"name":"Chongqing Key Laboratory of Pig Industry Sciences, Chongqing 402460, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keren","family":"Long","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0960-1529","authenticated-orcid":false,"given":"Lu","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6055-4692","authenticated-orcid":false,"given":"Long","family":"Jin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Sun","sequence":"additional","affiliation":[{"name":"Chongqing Academy of Animal Sciences, Chongqing 402460, China"},{"name":"Key Laboratory of Pig Industry Sciences, Ministry of Agriculture, Chongqing 402460, China"},{"name":"Chongqing Key Laboratory of Pig Industry Sciences, Chongqing 402460, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liangpeng","family":"Ge","sequence":"additional","affiliation":[{"name":"Chongqing Academy of Animal Sciences, Chongqing 402460, China"},{"name":"Key Laboratory of Pig Industry Sciences, Ministry of Agriculture, Chongqing 402460, China"},{"name":"Chongqing Key Laboratory of Pig Industry Sciences, Chongqing 402460, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuewei","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8681-7684","authenticated-orcid":false,"given":"Mingzhou","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jideng","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1891\/0730-0832.31.5.317","article-title":"Newborn transition to extrauterine life","volume":"31","author":"Wills","year":"2012","journal-title":"Neonatal Netw."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e33","DOI":"10.1891\/0730-0832.28.3.e33","article-title":"Fetal-to-neonatal transition\u2014What is normal and what is not?","volume":"28","author":"Askin","year":"2009","journal-title":"Neonatal Netw."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jmwh.2004.01.013","article-title":"Maternal, Fetal, & Neonatal Physiology: A Clinical Perspective, 2nd edition","volume":"49","year":"2004","journal-title":"J. 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