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Open AccessArticle

Long Non-Coding RNA CRNDE Is Involved in Resistance to EGFR Tyrosine Kinase Inhibitor in EGFR-Mutant Lung Cancer via eIF4A3/MUC1/EGFR Signaling

1
Division of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8602, Japan
2
Department of Electrical Engineering and Bioscience, Faculty of Science and Engineering, Waseda University, Shinjuku-ku, Tokyo 169-8555, Japan
3
AIST-Waseda University Computational Bio Big-Data Open Innovation Laboratory (CBBD-OIL), Shinjuku-ku, Tokyo 169-8555, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Robert Arthur Kratzke
Int. J. Mol. Sci. 2021, 22(8), 4005; https://doi.org/10.3390/ijms22084005
Received: 13 March 2021 / Revised: 2 April 2021 / Accepted: 9 April 2021 / Published: 13 April 2021
(This article belongs to the Section Molecular Oncology)
(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. View Full-Text
Keywords: EGFR-TKI; drug resistance; CRNDE; eIF4A3 EGFR-TKI; drug resistance; CRNDE; eIF4A3
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MDPI and ACS Style

Takahashi, S.; Noro, R.; Seike, M.; Zeng, C.; Matsumoto, M.; Yoshikawa, A.; Nakamichi, S.; Sugano, T.; Hirao, M.; Matsuda, K.; Hamada, M.; Gemma, A. Long Non-Coding RNA CRNDE Is Involved in Resistance to EGFR Tyrosine Kinase Inhibitor in EGFR-Mutant Lung Cancer via eIF4A3/MUC1/EGFR Signaling. Int. J. Mol. Sci. 2021, 22, 4005. https://doi.org/10.3390/ijms22084005

AMA Style

Takahashi S, Noro R, Seike M, Zeng C, Matsumoto M, Yoshikawa A, Nakamichi S, Sugano T, Hirao M, Matsuda K, Hamada M, Gemma A. Long Non-Coding RNA CRNDE Is Involved in Resistance to EGFR Tyrosine Kinase Inhibitor in EGFR-Mutant Lung Cancer via eIF4A3/MUC1/EGFR Signaling. International Journal of Molecular Sciences. 2021; 22(8):4005. https://doi.org/10.3390/ijms22084005

Chicago/Turabian Style

Takahashi, Satoshi; Noro, Rintaro; Seike, Masahiro; Zeng, Chao; Matsumoto, Masaru; Yoshikawa, Akiko; Nakamichi, Shinji; Sugano, Teppei; Hirao, Mariko; Matsuda, Kuniko; Hamada, Michiaki; Gemma, Akihiko. 2021. "Long Non-Coding RNA CRNDE Is Involved in Resistance to EGFR Tyrosine Kinase Inhibitor in EGFR-Mutant Lung Cancer via eIF4A3/MUC1/EGFR Signaling" Int. J. Mol. Sci. 22, no. 8: 4005. https://doi.org/10.3390/ijms22084005

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