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Current knowledge about the role of long non-coding RNAs (lncRNAs) in this phenomenon is insufficient. In this study, we screened the differentially expressed lncRNAs between osimertinib-sensitive and -resistant NSCLC cell lines, and determined that lnc-TMEM132D-AS1 was significantly upregulated in osimertinib-resistant NSCLC cells, as well as in the plasma of osimertinib-resistant NSCLC patients. Lnc-TMEM132D-AS1 markedly decreased the osimertinib sensitivity of NSCLC cells. After osimertinib exposure, it increased the cell proliferation and colony formation, decreased the cell apoptosis, and induced M2\/G-phase cell cycle arrest. After identifying its cytoplasmic localization, a functional lnc-TMEM132D-AS1-miRNA-mRNA interaction network and a protein\u2013protein interaction (PPI) network were constructed to analyze its putative target genes and biological functions. Lnc-TMEM132D-AS1 could directly bind to miR-766-5p and lead to the upregulation of ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1), resulting in an increase in cell proliferation. Moreover, upregulated ENTPD1 was also associated with enhanced tumor infiltration of immunosuppressive cells and poor prognosis in NSCLC patients. In summary, lnc-TMEM132D-AS1 plays a crucial role in osimertinib resistance. It may serve as a prognostic biomarker and a potential therapeutic target for acquired resistance to osimertinib in NSCLC.<\/jats:p>\n                  <jats:p\/>","DOI":"10.1039\/d2mo00261b","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T08:02:42Z","timestamp":1671609762000},"page":"238-251","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Lnc-TMEM132D-AS1 as a potential therapeutic target for acquired resistance to osimertinib in non-small-cell lung cancer"],"prefix":"10.1093","volume":"19","author":[{"given":"Nan","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Life Sciences, Chongqing Medical University Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qilin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutang","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Life Sciences, Chongqing Medical University Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunjie","family":"Wen","sequence":"additional","affiliation":[{"name":"Institute of Life Sciences, Chongqing Medical University Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaji","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Life Sciences, Chongqing Medical University Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meihua","family":"Bao","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University Changsha, 410219, China"},{"name":"Academician Workstation, Changsha Medical University Changsha, 410219, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanxiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Life Sciences, Chongqing Medical University Chongqing, China"},{"name":"Molecular Medicine Diagnostic and Testing Center, Chongqing Medical University Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"key":"2026010813031058100_bib1","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S0140-6736(21)00312-3","article-title":"Lung cancer","volume":"398","author":"Thai","year":"2021","journal-title":"Lancet"},{"key":"2026010813031058100_bib2","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.canlet.2021.05.009","article-title":"Cancer-associated fibroblasts in non-small cell lung cancer: Recent advances and future perspectives","volume":"514","author":"Zhang","year":"2021","journal-title":"Cancer Lett."},{"key":"2026010813031058100_bib3","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.lungcan.2021.06.002","article-title":"et al., The rapidly evolving landscape of novel targeted therapies in advanced non-small cell lung cancer","volume":"160","author":"Melosky","year":"2021","journal-title":"Lung Cancer"},{"key":"2026010813031058100_bib4","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.semcancer.2019.09.015","article-title":"Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer","volume":"61","author":"Harrison","year":"2020","journal-title":"Semin. 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