{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:25:41Z","timestamp":1777861541310,"version":"3.51.4"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>\n                    Natural antisense transcripts (NATs) from eukaryotic genes, known as long non-coding RNAs (lncRNAs), are long transcripts that do not encode proteins. NATs play diverse functional roles in regulating the transcription, stability, and translation of protein-coding genes at the epigenetic and post-transcriptional levels. Here, we outline recent studies on NAT-mediated RNA networks and discuss their potential as therapeutic targets across diseases. Interferon-\u03b11 (\n                    <jats:italic>IFNA1<\/jats:italic>\n                    ) mRNA expression is regulated by its overlapping antisense transcript\n                    <jats:italic>IFNA1-AS<\/jats:italic>\n                    through\n                    <jats:italic>IFNA1<\/jats:italic>\n                    mRNA\u2013\n                    <jats:italic>AS<\/jats:italic>\n                    duplex formation, and microRNA-sponging through common microRNA response elements (MREs) as competing endogenous RNAs. The competitive interactions between NATs and mRNA MRE(s) fine-tune mRNA and protein levels. The receptor tyrosine kinase, ephrin type-A receptor 2 (\n                    <jats:italic>EPHA2<\/jats:italic>\n                    ) mRNA and its antisense partner (\n                    <jats:italic>EPHA2-AS<\/jats:italic>\n                    ) are transcribed from the\n                    <jats:italic>EPHA2<\/jats:italic>\n                    gene and are overexpressed in breast cancer.\n                    <jats:italic>EPHA2-AS<\/jats:italic>\n                    interacts with\n                    <jats:italic>EPHA2<\/jats:italic>\n                    mRNA, forming an mRNA\u2013\n                    <jats:italic>AS<\/jats:italic>\n                    duplex that modulates both\n                    <jats:italic>EPHA2<\/jats:italic>\n                    mRNA and protein levels, potentially contributing to tumorigenesis; hence, it is a potential target for breast cancer treatment. RNA methylation, such as\n                    <jats:italic>N<\/jats:italic>\n                    <jats:sup>6<\/jats:sup>\n                    -methyladenosine, may also play a role in regulating gene expression in various diseases. NAT-targeted therapeutics, such as synthetic oligonucleotides, mRNA, and drugs, can be introduced into cells either directly or via extracellular vesicles and lipid nanoparticles. The administration of NAT-targeted therapeutics in animal disease models is useful for evaluating their efficacy. The mechanisms of NAT-mediated gene regulation should be further investigated to develop NAT-targeted therapeutics for the treatment of various diseases.\n                  <\/jats:p>","DOI":"10.3389\/fmolb.2026.1800738","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:24:44Z","timestamp":1777523084000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["RNA duplex formation and competing endogenous RNA, proposed as mechanisms in regulating expression of natural antisense transcripts- from hypotheses to potential therapeutic applications"],"prefix":"10.3389","volume":"13","author":[{"given":"Richi","family":"Nakatake","sequence":"first","affiliation":[{"name":"Department of Pancreatobiliary Surgery, Kansai Medical University","place":["Hirakata, Osaka, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Okuyama","sequence":"additional","affiliation":[{"name":"Department of Pancreatobiliary Surgery, Kansai Medical University","place":["Hirakata, Osaka, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tominori","family":"Kimura","sequence":"additional","affiliation":[{"name":"Comprehensive Research Organization for Science and Society, Ritsumeikan University","place":["Kusatsu, Shiga, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikio","family":"Nishizawa","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Ritsumeikan University","place":["Kusatsu, Shiga, Japan"]},{"name":"Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University","place":["Malang, Indonesia"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1063636","DOI":"10.3389\/fonc.2023.1063636","article-title":"The lncRNA epigenetics: the significance of m6A and m5C lncRNA modifications in cancer","volume":"13","author":"Cusenza","year":"2023","journal-title":"Front. 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