J Pathol Transl Med.  2018 Sep;52(5):275-282. 10.4132/jptm.2018.07.29.

Differential MicroRNA Expression between EGFR T790M and L858R Mutated Lung Cancer

• Kim JY
• Lee WJ
• Park HY
• Kim A
• Shin DH
• Lee CH

• KMID: 2422093
• DOI: http://doi.org/10.4132/jptm.2018.07.29

Abstract

BACKGROUND
MicroRNAs (miRNAs) are short, non-coding RNAs that mediate post-transcriptional gene regulation. They are commonly deregulated in human malignancies, including non-small cell lung cancer (NSCLC). The aim of this study is to investigate miRNA expression in T790M-mutated NSCLC resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors.
METHODS
Six cases of resected NSCLC harboring the T790M mutation were examined. We performed miRNA time polymerase chain reaction (PCR) array profiling using EGFR T790M-mutated NSCLC and L858R-mutated NSCLC. Once identified, miRNAs that were differentially expressed between the two groups were validated by quantitative real-time polymerase chain reaction (qRT-PCR).
RESULTS
miRNA PCR array profiling revealed three up-regulated miRNAs whose expression levels were altered 4.0-fold or more in the EGFR T790M mutation group than in the L858R group: miR-1 (fold change, 4.384), miR-196a (fold change, 4.138), and miR-124 (fold change, 4.132). The three differentially expressed miRNAs were validated by qRT-PCR, and they were found to be overexpressed in the T790M group relative to L858R group. In particular, expression levels of miR-1 and miR-124 were significantly higher in the T790M group (p-value of miR-1 = .004, miR-124 = .007, miR-196a = .096).
CONCLUSIONS
MiR-1, miR-124, and miR-196a are overexpressed in EGFR T790M mutated NSCLC.

Keyword

MicroRNAs; Lung neoplasms; EGFR T790M mutation

MeSH Terms

Carcinoma, Non-Small-Cell Lung
Humans
Lung Neoplasms*
Lung*
MicroRNAs*
Polymerase Chain Reaction
Protein-Tyrosine Kinases
Real-Time Polymerase Chain Reaction
Receptor, Epidermal Growth Factor
RNA, Untranslated
MicroRNAs
Protein-Tyrosine Kinases
RNA, Untranslated
Receptor, Epidermal Growth Factor

Figure

• 

  Fig. 1. Representative microphotograph of EGFR T790M mutated adenocarcinoma (predominantly acinar pattern of case 5). EGFR, epidermal growth factor receptor.

• 

  Fig. 2. Expression of miRNAs (A, miR-1; B, miR-124; and C, miR-196a) in EGFR T790M and L858R groups. EGFR, epidermal growth factor receptor.

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