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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,7,21]]},"abstract":"<jats:p>\n                    Small nucleolar RNAs (snoRNAs) play crucial regulatory roles in various cancers. However, the mechanisms by which snoRNAs regulate N6-methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) modifications in colorectal cancer (CRC) remain unclear. This study systematically deciphered the precise interaction mechanism between\n                    <jats:italic toggle=\"yes\">SNORD78<\/jats:italic>\n                    and the m\n                    <jats:sup>6<\/jats:sup>\n                    A reader IMP2 in CRC. We demonstrate that\n                    <jats:italic toggle=\"yes\">SNORD78<\/jats:italic>\n                    specifically stabilizes IMP2 to activate the PIK3CD-CHKA-Kennedy pathway in an m\n                    <jats:sup>6<\/jats:sup>\n                    A-dependent manner, promoting endoplasmic reticulum stress (ERS) and phosphatidylcholine (PC) biosynthesis, thereby driving CRC. Conversely, the\n                    <jats:italic toggle=\"yes\">SNORD78<\/jats:italic>\n                    -targeting antisense oligonucleotide (ASO), ASO-78, effectively suppresses ERS and PC levels, inhibiting CRC progression. Mechanistically,\n                    <jats:italic toggle=\"yes\">SNORD78<\/jats:italic>\n                    , relying on the \u201cUAAUGA\u201d element in its C-D box region, specifically binds to the Lys221 ubiquitination site of IMP2, blocking TRIM25-mediated degradation of IMP2 and maintaining its stability. IMP2 enhanced the stability and translation of the target mRNAs\n                    <jats:italic toggle=\"yes\">PIK3CD<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">CHKA<\/jats:italic>\n                    by recognizing their corresponding m\n                    <jats:sup>6<\/jats:sup>\n                    A positions, m\n                    <jats:sup>6<\/jats:sup>\n                    A-3208 and m\n                    <jats:sup>6<\/jats:sup>\n                    A-1619, respectively, to reshape the phosphatidylcholine metabolite profile in CRC cells. In terms of potential therapeutic strategies, the ASO-78 can significantly inhibit CRC cell proliferation, reduce ERS levels, and decrease phosphatidylcholine content. The combination of ASO-78 and IMP2 inhibitor IMP2-IN1, by dual blocking of the\n                    <jats:italic toggle=\"yes\">SNORD78<\/jats:italic>\n                    \u2013IMP2 axis, exhibits an excellent proliferation-inhibiting effect in CRC organoids. This study not only reveals a mechanism by which the\n                    <jats:italic toggle=\"yes\">SNORD78<\/jats:italic>\n                    \u2013IMP2 interaction regulates CRC occurrence and development but also provides theoretical basis for innovative therapeutic strategies for precise targeting of tumor snoRNA-m\n                    <jats:sup>6<\/jats:sup>\n                    A reader interactions.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2531283123","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T16:17:56Z","timestamp":1784045876000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Oncogenic snoRNA\n                    <i>SNORD78<\/i>\n                    fuels colorectal cancer by protecting the m\n                    <sup>6<\/sup>\n                    A reader IMP2 to enhance phospholipid metabolism"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4624-9944","authenticated-orcid":false,"given":"Yingqi","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, China Medical University","place":["Shenyang, The People\u2019s Republic of China"]},{"name":"Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation; 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