MicroRNA Regulation of Messenger RNA in Lung Neuroendocrine Cell Lines

Abstract

Introduction: Lung neuroendocrine neoplasms (NENs) are rare lung cancers whose pathomechanisms are poorly understood. MicroRNAs (miRNAs) are small, non-coding RNAs (19-24 nucleotides in length) that negatively regulate messenger RNA (mRNA) expression. Each miRNA targets a specific set of mRNAs to regulate. To better understand the molecular biology of lung NENs, we investigated miRNA-mediated mRNA regulation in NEN and non-NEN cell lines.
 Methods: NEN and non-NEN cell line expression profiles were relative frequency normalized before undergoing outlier and batch detection. We identified the top 1% most highly expressed miRNAs in all cell lines, NEN cell lines, and non-NEN cell lines. Next, we identified differentially expressed miRNAs and mRNAs between NEN and non-NEN types. We used the Bio-miRTa target prediction algorithm to identify the putative mRNA targets of key miRNAs. Key miRNAs are miRNAs uniquely expressed in NENs compared to non-NENs types. We subsequently determined the likely biological pathways of the predicted targets using the g:Profiler software.
 Results: High and differential expression analyses identified miRs-375, -200c, -100, -141, and -7 to be the key miRNAs in lung NEN cell lines compared to non-NEN types. 8014 differentially expressed mRNAs were identified between NEN and non-NEN types. 3916 predicted mRNA targets were identified, which collectively participated in pathways from 21 different categories of cellular function.
 Discussion: Comparisons between NEN and non-NEN cell lines identified the key miRNAs of lung NENs to be miRs-375, -200c, -100, -141, and -7. The identified biological pathways of the predicted targets highlight the functional differences between NENs and non-NENs.
 Conclusions: Our high and differential expression analyses results identified the key miRNAs in lung NEN cell lines. The biological pathways of the predicted mRNA targets of key miRNAs were also identified. The results generated in this study help to differentiate NENs from non-NENs, which provides a deeper insight into the pathomechanisms of lung NENs. These results also expand our current knowledge in lung NEN biology, which may facilitate the future development of NEN specific drugs and diagnostic tests.