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While several genetic alterations have been implicated in tFL, the role of microenvironmental interactions and post-transcriptional regulation by non-coding RNAs remains poorly understood. We performed the first matched profiling of mRNAs and short non-coding RNAs (miRNAs) in paired FL and tFL samples (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200911 pairs). This revealed differential expression of 1,075 mRNAs and 19 miRNAs, including repression of\n                    <jats:italic>miR-29<\/jats:italic>\n                    family in tFL (\n                    <jats:italic>miR-29a\/b\/c<\/jats:italic>\n                    ). Further analysis uncovered that MYC directly transcriptionally represses\n                    <jats:italic>miR-29<\/jats:italic>\n                    in tFL, resulting in the upregulation of its target TRAF4. TRAF4 upregulation contributes to CD40 signaling being strongly activated in tFL and supports malignant B-cell proliferation. Notably, this increased CD40 pathway activity in 90% of\u00a0tFL and\u00a0contrasted with the reduced T-cell numbers in tFL niches. Thus, the MYC-\n                    <jats:italic>miR-29<\/jats:italic>\n                    -TRAF4 axis and increased CD40 signaling propensity may serve as tFL cells\u2019 adaptation to reduced numbers of CD40L+ T-cells. Moreover, lower levels of all\n                    <jats:italic>miR-29s(a\/b\/c)<\/jats:italic>\n                    were associated with shorter overall survival (OS) and progression-free survival in FL (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009185), including in a multivariate analysis. Low\n                    <jats:italic>miR-29c<\/jats:italic>\n                    was also associated with shorter OS in a validation cohort (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200992) from the first-line R-CHOP therapy clinical trial (SWOG S0016, NCT00006721).\n                  <\/jats:p>","DOI":"10.1038\/s41375-026-02868-8","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T09:12:34Z","timestamp":1771492354000},"page":"759-772","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Repression of miR-29 via MYC leads to increased CD40 signaling in transformed follicular lymphoma"],"prefix":"10.1038","volume":"40","author":[{"given":"Daniel","family":"Filip","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Litzmanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Androniki","family":"Michaelou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8671-5700","authenticated-orcid":false,"given":"Filip","family":"Kledus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Devan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5757-0424","authenticated-orcid":false,"given":"Miroslav","family":"Boudny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7185-6119","authenticated-orcid":false,"given":"Eva","family":"Hoferkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonali","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0234-6470","authenticated-orcid":false,"given":"Vaclav","family":"Seda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0243-5983","authenticated-orcid":false,"given":"Pedro 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