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- Title
Long Non-Coding RNA CRNDE Is Involved in Resistance to EGFR Tyrosine Kinase Inhibitor in EGFR-Mutant Lung Cancer via eIF4A3/MUC1/EGFR Signaling.
- Authors
Takahashi, Satoshi; Noro, Rintaro; Seike, Masahiro; Zeng, Chao; Matsumoto, Masaru; Yoshikawa, Akiko; Nakamichi, Shinji; Sugano, Teppei; Hirao, Mariko; Matsuda, Kuniko; Hamada, Michiaki; Gemma, Akihiko
- Abstract
(1) Background: Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is an intractable problem for many clinical oncologists. The mechanisms of resistance to EGFR-TKIs are complex. Long non-coding RNAs (lncRNAs) may play an important role in cancer development and metastasis. However, the biological process between lncRNAs and drug resistance to EGFR-mutated lung cancer remains largely unknown. (2) Methods: Osimertinib- and afatinib-resistant EGFR-mutated lung cancer cells were established using a stepwise method. A microarray analysis of non-coding and coding RNAs was performed using parental and resistant EGFR-mutant non-small cell lung cancer (NSCLC) cells and evaluated by bioinformatics analysis through medical-industrial collaboration. (3) Results: Colorectal neoplasia differentially expressed (CRNDE) and DiGeorge syndrome critical region gene 5 (DGCR5) lncRNAs were highly expressed in EGFR-TKI-resistant cells by microarray analysis. RNA-protein binding analysis revealed eukaryotic translation initiation factor 4A3 (eIF4A3) bound in an overlapping manner to CRNDE and DGCR5. The CRNDE downregulates the expression of eIF4A3, mucin 1 (MUC1), and phospho-EGFR. Inhibition of CRNDE activated the eIF4A3/MUC1/EGFR signaling pathway and apoptotic activity, and restored sensitivity to EGFR-TKIs. (4) Conclusions: The results showed that CRNDE is associated with the development of resistance to EGFR-TKIs. CRNDE may be a novel therapeutic target to conquer EGFR-mutant NSCLC.
- Subjects
PROTEIN-tyrosine kinase inhibitors; NON-coding RNA; LUNG cancer; EPIDERMAL growth factor receptors; NON-small-cell lung carcinoma; RNA-binding proteins; LINCRNA
- Publication
International Journal of Molecular Sciences, 2021, Vol 22, Issue 8, p4005
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms22084005