Purpose: Gefitinib is a widely used therapeutic drug for non-small cell lung cancer (NSCLC), and its acquired resistance has become one of the barriers to the successful use of the drugs to treat NSCLC patients. Long non-coding RNA (lncRNA) has an essential role in developing cancer drug resistance. Hence, this study aimed to investigate the effect and modulatory mechanisms of lncRNA MCF2L-AS1 in Gefitinib resistance in NSCLC.
Methods: IBEAS-2B and A549 cells and human NSCLC tissues were used. A549/GR cell line was constructed by continuous exposure to Gefitinib. Cell viability, apoptosis, migration, colony formation, and protein expression studies were done in transfected cells. Interactions of MCF2L-AS1, ELAVL1, and Cyclin D1 (CCND1 was also investigated.
Results: In patients with Gefitinib-resistant NSCLC, MCF2L-AS1 and CCND1 were both up-regulated. Knockdown of MCF2L-AS1 reduced Gefitinib-resistant NSCLC cell progression, indicating that inhibition of MCF2L-AS1 restrained Gefitinib-resistant NSCLC. Mechanically, MCF2L-AS1 enhanced CCND1 mRNA stability via combining with ELAVL1, thereby elevating the resistance of NSCLC cells to Gefitinib. Moreover, E2F1 could transcriptionally up-regulate MCF2L-AS1.
Conclusion: The results manifest that lncRNA MCF2L-AS1, as an oncogene of NSCLC, controls CCDN1 via ELAVL1 to drive the growth of NSCLC cells and Gefitinib resistance.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.18388/abp.2020_6118 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
TLE1 corepressor promotes gefitinib resistance in lung cancer A549 cells via E‑cadherin silencing.
Biomed Rep
March 2025
Department of Biology, Xavier University of Louisiana, New Orleans, LA 70125, USA.
As a putative lung specific oncogene, the transducin-like enhancer of split 1 (TLE1) corepressor drives an anti-apoptotic and pro-epithelial-mesenchymal transition (EMT) gene transcriptional programs in human lung adenocarcinoma (LUAD) cells, thereby promoting anoikis resistance and tumor aggressiveness. Through its survival- and EMT-promoting gene regulatory programs, TLE1 may impact drug sensitivity and resistance in lung cancer cells. In the present study, a novel function of TLE1 was uncovered as an inhibitor of the antitumor effects of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) gefitinib in the human LUAD cell line A549, which exhibits moderate sensitivity to EGFR-TKI.
View Article and Find Full Text PDFOsimertinib as Second- and ≥Third-Line Treatment in Advanced and Recurrence EGFR-Mutant NSCLC Patients Harboring Acquired T790M Mutation.
Cancers (Basel)
December 2024
Department of Chest Medicine, Taichung Veterans General Hospital, No. 1650, Sect. 4, Taiwan Boulevard, Taichung 407, Taiwan.
Background/objectives: Osimertinib is a standard sequential therapy for advanced and recurrent Epidermal Growth Factor Receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients with the T790M mutation, following treatment with first- or second-generation EGFR Tyrosine Kinase Inhibitors (TKIs). This study aims to investigate the differences in clinical outcomes between osimertinib as a 2nd-line treatment and as a ≥3rd-line treatment in this patient population.
Methods: Between September 2014 and March 2023, we enrolled advanced and recurrent T790M + NSCLC patients who had received osimertinib as sequential treatment for analysis.
Cytotoxic activity of C polyacetylenes from the roots of Glehnia littoralis against drug-resistant colorectal and lung cancer cells.
J Nat Med
January 2025
College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea.
Article Synopsis
- The study identified cytotoxic compounds, falcarinol and falcarindiol, from the roots of Glehnia littoralis, effective against both sensitive and resistant colorectal and lung cancer cells.
- Researchers isolated 13 polyacetylenes, including a new compound (3R,11R)-11-hyroxy-isofalcarinolone, using advanced chemical analysis techniques.
- Findings suggest that while these compounds show potential for anticancer development, their stability needs further investigation since some newly purified compounds did not exhibit expected activity.
Aidi injection inhibits the migration and invasion of gefitinib-resistant lung adenocarcinoma cells by regulating the PLAT/FAK/AKT pathway.
Chin Med
January 2025
Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China.
Background: With extended gefitinib treatment, the therapeutic effect in some non-small cell lung cancer (NSCLC) patients declined with the development of drug resistance. Aidi injection (ADI) is utilized in various cancers as a traditional Chinese medicine prescription. This study explores the molecular mechanism by which ADI, when combined with gefitinib, attenuates gefitinib resistance in PC9GR NSCLC cells.
View Article and Find Full Text PDFFolic Acid-Modified Milk Exosomes Delivering c-Kit siRNA Overcome EGFR-TKIs Resistance in Lung Cancer by Suppressing mTOR Signaling and Stemness.
Int J Biol Sci
January 2025
Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China, 610041.
Article Synopsis
- The study addresses a common issue in lung cancer treatment, where patients develop resistance to EGFR-TKIs like gefitinib, leading to worse outcomes.
- The researchers developed a novel therapy using folic acid-modified milk exosomes loaded with c-kit siRNA (FA-mExo-siRNA-c-kit) to counteract this resistance by targeting the c-kit gene, which is linked to stemness traits in cancer cells.
- Results showed that this approach not only reduced c-kit expression and stemness characteristics but also slowed tumor growth and improved survival in experimental models, highlighting its potential as a new treatment strategy for resistant lung cancer.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!