{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:49:14Z","timestamp":1789170554559,"version":"build-2803163510"},"reference-count":56,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T00:00:00Z","timestamp":1673913600000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82003101"],"award-info":[{"award-number":["82003101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31570800"],"award-info":[{"award-number":["31570800"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The therapeutic value of targeted therapies in patients with lung cancer is reduced when tumours acquire secondary resistance after an initial period of successful treatment. However, the molecular events behind the resistance to targeted therapies in lung cancer remain largely unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To discover the important role and mechanism of lncRNA BC in promoting tumor metastasis and influencing clinical prognosis of LUAD. Materials &amp; Methods: Microarrays were used to screen a comprehensive set of lncRNAs with differential expression profiles in lung cancer cells. The functional role and mechanism of lncRNA were further investigated by gain\u2010 and loss\u2010of\u2010function assays. RNA pull\u2010down, protein assays, and mass spectrometry were used to identify proteins that interacted with lncRNA. TaqMan PCR was used to measure lncRNA in lung adenocarcinoma and adjacent nontumor tissues from 428 patients. The clinical significance of lncRNA identified was statistically confirmed in this cohort of patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this study, we show that the long non\u2010coding RNA BC009639 (BC) is involved in acquired resistance to EGFR\u2010targeted therapies. Among the 235 long non\u2010coding RNAs that were differentially expressed in lung cancer cell lines, with different metastatic potentials, BC promoted growth, invasion, metastasis, and resistance to EGFR\u2010tyrosine kinase inhibitors (EGFR\u2010TKIs), both in vitro and in vivo. BC was highly expressed in 428 patients with lung adenocarcinoma (LUAD) and high BC expression correlated with reduced efficacy of EGFR\u2010TKI therapy. To uncover the molecular mechanism of BC\u2010mediated EGFR\u2010TKI resistance in lung cancer, we screened and identified nucleolin and hnRNPK that interact with BC. BC formed the splicing complex with nucleolin and hnRNPK to facilitate the production of a non\u2010protein\u2010coding inositol monophosphatase domain containing 1 (IMPAD1) splice variant, instead of the protein\u2010coding variant. The BC\u2010mediated alternative splicing (AS) of IMPAD1 resulted in the induction of the epithelial\u2013mesenchymal transition and resistance to EGFR\u2010TKI in lung cancer. High BC expression correlated with clinical progress and poor survival among 402 patients with LUAD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Disscussion<\/jats:title><jats:p>Through alternative splicing, BC boosted the non\u2010coding IMPAD1\u2010203 transcript variant while suppressing the IMPAD1\u2010201 variant. In order to control the processing of pre\u2010mRNA, BC not only attracted RNA binding proteins (NCL, IGF2BP1) or splicing factors (hnRNPK), but also controlled the formation of the splicing\u2010regulator complex by creating RNA\u2010RNA\u2010duplexes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results reveal an important role for BC in mediating resistance to EGFR\u2010targeted therapy in LUAD through IMPAD1 AS and in implication for the targeted therapy resistance.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1129","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T04:18:29Z","timestamp":1674015509000},"source":"Crossref","is-referenced-by-count":23,"title":["LncRNA BC promotes lung adenocarcinoma progression by modulating IMPAD1 alternative splicing"],"prefix":"10.1002","volume":"13","author":[{"given":"Qi Wen","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Integrative Oncology Fudan University Shanghai Cancer Center  Shanghai P. 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