Lnc-TMEM132D-AS1 as a potential therapeutic target for acquired resistance to osimertinib in non-small-cell lung cancer
作者全名："Wang, Nan; Zhao, Qilin; Huang, Yutang; Wen, Chunjie; Li, Yaji; Bao, Meihua; Wu, Lanxiang"
作者地址："[Wang, Nan; Huang, Yutang; Wen, Chunjie; Li, Yaji; Wu, Lanxiang] Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China; [Zhao, Qilin] Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiothorac Surg, Chongqing, Peoples R China; [Bao, Meihua] Changsha Med Univ, Hunan Key Lab Res & Dev Novel Pharmaceut Preparat, Changsha 410219, Peoples R China; [Bao, Meihua] Changsha Med Univ, Academician Workstation, Changsha 410219, Peoples R China; [Wu, Lanxiang] Chongqing Med Univ, Mol Med Diagnost & Testing Ctr, Chongqing, Peoples R China"
通信作者："Wu, LX (通讯作者)，Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China.; Wu, LX (通讯作者)，Chongqing Med Univ, Mol Med Diagnost & Testing Ctr, Chongqing, Peoples R China."
来源：MOLECULAR OMICS
ESI学科分类：BIOLOGY & BIOCHEMISTRY
WOS号：WOS:000914689100001
JCR分区：Q3
影响因子：3
年份：2023
卷号：19
期号：3
开始页：238
结束页：251
文献类型：Article
关键词：
摘要："Acquired resistance is a major obstacle to the therapeutic efficacy of osimertinib in non-small-cell lung cancer (NSCLC). 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-protein 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."
基金机构："Natural Science Foundation of China [82073938, 82274023]; Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0246, cstc2020jcyj-msxmX0258]; Program for Youth Innovation in Future Medicine, Chongqing Medical University [W0093]; Scientific and Technological Research Program of Yuzhong District, Chongqing [20200102]; Scientific and Technological Research Program of Chongqing Municipal Education Commission [KJQN202200432]"
基金资助正文："This work was supported by the Natural Science Foundation of China (No. 82073938 and 82274023), the Natural Science Foundation of Chongqing (No. cstc2020jcyj-msxmX0246 and cstc2020jcyj-msxmX0258), the Program for Youth Innovation in Future Medicine, Chongqing Medical University (No. W0093), the Scientific and Technological Research Program of Yuzhong District, Chongqing (No. 20200102), and the Scientific and Technological Research Program of Chongqing Municipal Education Commission (No. KJQN202200432)."
