Targeting Nicotinamide N-Methyltransferase and miR-449a in EGFR-TKI-Resistant Non-Small-Cell Lung Cancer Cells

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used clinically as target therapies for lung cancer patients, but the occurrence of acquired drug resistance limits their efficacy. Nicotinamide N-methyltransferase (NNMT), a cancer-associated metabolic enzyme, is commonly overexpressed in various human tumors. Emerging evidence also suggests a crucial loss of function of microRNAs (miRNAs) in modulating tumor progression in response to standard therapies. However, their precise roles in regulating the development of drug-resistant tumorigenesis are still poorly understood. Herein, we established EGFR-TKI-resistant non-small-cell lung cancer (NSCLC) models and observed a negative correlation between the expression levels of NNMT and miR-449a in tumor cells. Additionally, knockdown of NNMT suppressed p-Akt and tumorigenesis, while re-expression of miR-449a induced phosphatase and tensin homolog (PTEN), and inhibited tumor growth. Furthermore, yuanhuadine, an antitumor agent, significantly upregulated miR-449a levels while critically suppressing NNMT expression. These findings suggest a novel therapeutic approach for overcoming EGFR-TKI resistance to NSCLC treatment.

• Publication year

  2018

• Venue

  Molecular Therapy: Nucleic Acids

• Publication date

  2018-03-29

• Fields of study

  Medicine

• Identifiers
  DOI 10.1016/j.omtn.2018.03.011PMID 29858080PMCID 5992482
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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