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However, the molecular mechanisms underlying NSCLC growth and progression remain largely unclear. Here, EP300-AS1 is identified as a critical tumor-suppressive long non-coding RNA (lncRNA) in NSCLC. EP300-AS1 inhibits NSCLC cell growth and metastasis both in vitro and in vivo, and is associated with better clinical outcomes. The function of EP300-AS1 depends on EP300-AS1-PTBP1 interaction and PTBP1-mediated PRMT5 mRNA stability. EP300-AS1 binds directly to PTBP1, preventing its cytoplasmic translocation and PTBP1-PRMT5 mRNA complex formation in NSCLC. In the absence of PTBP1 binding to the PRMT5 mRNA 3\u2019-UTR, PRMT5 mRNA stability and expression are reduced. PTBP1 knockdown or PRMT5 inhibition abolishes EP300-AS1-regulated NSCLC cell proliferation, migration, and invasion. In patients with lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), EP300-AS1 expression is negatively correlated with PRMT5 expression. Overall, these findings establish the EP300-AS1-PTBP1-PRMT5 axis as a key regulatory pathway in NSCLC progression, providing a novel regulatory mechanism and a promising target for NSCLC prediction and therapy.<\/jats:p>","DOI":"10.1038\/s41419-025-07931-3","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T17:40:55Z","timestamp":1754934055000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["LncRNA EP300-AS1 interacts with PTBP1 to destabilize PRMT5 mRNA and suppresses NSCLC growth and metastasis"],"prefix":"10.1038","volume":"16","author":[{"given":"Jingyi","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongyu","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songze","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2323-5331","authenticated-orcid":false,"given":"Deyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"key":"7931_CR1","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/nrc3775","volume":"14","author":"Z Chen","year":"2014","unstructured":"Chen Z, Fillmore CM, Hammerman PS, Kim CF, Wong KK. 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