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However, the regulatory mechanisms and clinical significance of tsRNAs in colorectal cancer (CRC) remain unclear. In this study, PANDORA\u2010seq was used as an exploratory screen of CRC tissues, paired adjacent tissues, and CRC plasma samples, followed by validation in larger independent cohorts. Quantitative real\u2010time PCR quantified mt\u20105\u2019\u2010tiRNA\u2010Tyr levels in tissues, plasma, and cells. Functional assays assessed the role of mt\u20105\u2019\u2010tiRNA\u2010Tyr in CRC. Mechanistic studies utilized RNA pull\u2010down, mass spectrometry, RNA immunoprecipitation, western blotting, and Co\u2010immunoprecipitation. Results revealed that mt\u20105\u2019\u2010tiRNA\u2010Tyr was significantly upregulated in CRC plasma and tissues. In vitro and in vivo studies demonstrated its oncogenic potential. Mechanistic assays showed that mt\u20105\u2019\u2010tiRNA\u2010Tyr was enriched with HARS2 in RNA pull\u2010down\/RIP assays and associated with reduced HARS2\u2010mt\u2010tRNA\u2010His association, increased HARS2 K91 succinylation, impaired mitochondrial protein translation, and mitochondrial damage. Moreover, succinate accumulation creates a positive feedback loop that enhances CRC proliferation. This study identifies a novel oncogenic tsRNA and uncovers a mechanism by which mt\u20105\u2019\u2010tiRNA\u2010Tyr promotes CRC proliferation through HARS2 succinylation, supporting further evaluation of plasma mt\u20105\u2019\u2010tiRNA\u2010Tyr as a candidate circulating biomarker for CRC.<\/jats:p>","DOI":"10.1002\/advs.77042","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:21:15Z","timestamp":1787322075000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel tRNA Half mt\u20105\u2019\u2010tiRNA\u2010Tyr Promotes Colorectal Cancer Proliferation via Inducing HARS2 Succinylation"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8118-5347","authenticated-orcid":false,"given":"Xinliang","family":"Gu","sequence":"first","affiliation":[{"name":"General Clinical Research Center Nanjing First Hospital Nanjing Medical University  Nanjing 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