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Sodium-myoinositol cotransporter-1 (SMIT1) acts as an oncogene in different types of cancer. This study aimed to explore [1] the role of SMIT1 in DLBCL development, and [2] whether N6-Methyladenosine (m6A) modifications were responsible for high SMIT1 expression within DLBCL tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Expression of SMIT1 was modulated by a eukaryotic SMIT1-expressing plasmid or a plasmid specific to SMIT1-targeting shRNA. The impacts of SMIT1 overexpression or knockdown on DLBCL cell proliferation, cell cycle, and apoptosis were evaluated using cell-counting-kit-8, flow cytometry and western blot assays. A DLBCL cell-derived tumor xenograft was established to further assess the tumorigenicity of SMIT1. qPCR, RIP-qPCR, MeRIP-qPCR, dual luciferase reporter and western blot assays were employed to explore whether high SMIT1 expression was associated with WTAP\/YTHDF1-mediated m6A modifications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Bioinformatics analysis showed that high SMIT1 expression in DLBCL was positively associated with poor prognosis, survival-related markers and m6A methyltransferase Wilms tumor 1-associated protein (WTAP). SMIT1 overexpression supported proliferation and cell cycle progression of DLBCL cells, while its depletion induced proliferation suppression, G1-S phase arrest and apoptosis of DLBCL cells. Decreased myo-inositol, phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3) contents and AKT phosphorylation level were observed after SMIT1 silencing, yet increased after SMIT1 overexpression in DLBCL cells. In vivo, SMIT1 silencing delayed tumor growth and induced AKT inactivation. SMIT1 silencing-induced anti-DLBCL role was partly weakened by the addition of AKT agonist SC-79. Furthermore, we found that upregulation of WTAP enhanced the SMIT1 m6A and mRNA levels. WTAP-regulated SMIT1 m6A was recognized and stabilized by YTH N6-Methyladenosine RNA Binding Protein F1 (YTHDF1) m6A reader.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study uncovers a novel oncogenic axis in DLBCL, where SMIT1\u2019s carcinogenic potential is epigenetically modulated by WTAP\/YTHDF1-mediated m6A methylation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-025-07303-7","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T11:40:34Z","timestamp":1763466034000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sodium-myoinositol cotransporter-1 downstream of m6A methyltransferase WTAP exerts a potential carcinogenicity in diffuse large B-cell lymphoma progression"],"prefix":"10.1186","volume":"23","author":[{"given":"Xinyang","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowei","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"7303_CR1","doi-asserted-by":"publisher","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","volume":"36","author":"R Alaggio","year":"2022","unstructured":"Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IBO, Berti E, et al. 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Informed consent was obtained from the subject. The research involving animals was approved by the Institutional Animal Care and Use Committee of Shengjing Hospital of China Medical University (approval ID: 2024PS1337K).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1310"}}