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The expression of BRG1 engages in pre-mRNA splicing through interacting RNPs in cancers; however, the detailed molecular pathology of how BRG1and CHD7 relate to cancer development remains largely unveiled. This study demonstrated novel post-transcriptional regulation of BRG1 in EMT and relationship with FIR\u0394exon2, which is a splicing variant of the far-upstream element-binding protein (FUBP) 1-interacting repressor (FIR) lacking exon 2, which fails to repress <jats:italic>c-myc<\/jats:italic> transcription in cancers. Previously, we have reported that FIR complete knockout mice (<jats:italic>FIR<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) was embryonic lethal before E9.5, suggesting FIR is crucial for development. FIR\u0394exon2 acetylated H3K27 on promoter of BRG1 by CHIP-sequence and suppressed BRG1 expression post-transcriptionally; herein BRG1 suppressed Snai1 that is a transcriptional suppressor of E-cadherin that prevents cancer invasion and metastasis. Ribosomal proteins, hnRNPs, splicing-related factors, poly (A) binding proteins, mRNA-binding proteins, tRNA, DEAD box, and WD-repeat proteins were identified as co-immunoprecipitated proteins with FIR and FIR\u0394exon2 by redoing exhaustive mass spectrometry analysis. Furthermore, the effect of FIR\u0394exon2 on <jats:italic>FGF8<\/jats:italic> mRNA splicing was examined as an indicator of neural development due to impaired CHD7 revealed in CHARGE syndrome. Expectedly, siRNA of FIR\u0394exon2 altered <jats:italic>FGF8<\/jats:italic> pre-mRNA splicing, indicated close molecular interaction among FIR\u0394exon2, BRG1 and CHD7. FIR\u0394exon2 mRNA was elevated in human gastric cancers but not in non-invasive gastric tumors in <jats:italic>FIR<\/jats:italic><jats:sup><jats:italic>+\/<\/jats:italic><\/jats:sup> mice (K19-Wnt1\/C2mE x <jats:italic>FIR<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup>). The levels of FIR family (FIR, FIR\u0394exon2 and PUF60), BRG1, Snai1, FBW7, E-cadherin, c-Myc, cyclin-E, and SAP155 increased in the gastric tumors in <jats:italic>FIR<\/jats:italic><jats:sup><jats:italic>+\/\u2212<\/jats:italic><\/jats:sup> mice compared to those expressed in wild-type mice. FIR family, Snai1, cyclin-E, BRG1, and c-Myc showed trends toward higher expression in larger tumors than in smaller tumors in Gan-mice (K19-Wnt1\/C2mE). The expressions of BRG1 and Snai1 were positively correlated in the gastric tumors of the Gan-mice. Finally, BRG1 is a candidate substrate of F-box and WD-repeat domain-containing 7 (FBW7) revealed by three-dimensional crystal structure analysis that the U2AF-homology motif (UHM) of FIR\u0394exon2 interacted with tryptophan-425 and asparate-399 (WD)-like motif in the degron pocket of FBW7 as a UHM-ligand motif. Together, FIR\u0394exon2 engages in multi-step post-transcriptional regulation of BRG1, affecting EMT through the BRG1\/Snai1\/E-cadherin pathway and promoting tumor proliferation and invasion of gastric cancers.<\/jats:p>","DOI":"10.1038\/s41389-020-0205-4","type":"journal-article","created":{"date-parts":[[2020,2,18]],"date-time":"2020-02-18T16:14:29Z","timestamp":1582042469000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Post-transcriptional regulation of BRG1 by FIR\u0394exon2 in gastric cancer"],"prefix":"10.1038","volume":"9","author":[{"given":"Guzhanuer","family":"Ailiken","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kouichi","family":"Kitamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyuji","family":"Hoshino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mamoru","family":"Satoh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuko","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4168-996X","authenticated-orcid":false,"given":"Toshinari","family":"Minamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4014-2789","authenticated-orcid":false,"given":"Bahityar","family":"Rahmutulla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sohei","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayuki","family":"Kano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9761-1750","authenticated-orcid":false,"given":"Tomoaki","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6980-5515","authenticated-orcid":false,"given":"Atsushi","family":"Kaneda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumio","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisahiro","family":"Matsubara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuyuki","family":"Matsushita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,2,18]]},"reference":[{"key":"205_CR1","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1038\/nature08733","volume":"463","author":"R Bajpai","year":"2010","unstructured":"Bajpai, R. et al. 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