| Title: |
Modulation of the Oncogenic LINE-1 Regulatory Network in Non-Small Cell Lung Cancer by Exosomal miRNAs. |
| Authors: |
Hassanin, Abeer A. I.1,2 (AUTHOR) ahassanin@tamu.edu, Ramos, Kenneth S.1 (AUTHOR) kramos@tamu.edu |
| Source: |
International Journal of Molecular Sciences. Oct2024, Vol. 25 Issue 19, p10674. 16p. |
| Subject Terms: |
*NON-small-cell lung carcinoma, *GENE expression, *EXOSOMES, *LUNG cancer, *EPITHELIAL cells |
| Abstract: |
Several microRNAs (miRNAs), including miR-221-5p, Let-7b-5p, miR-21-5p, miR-9-5p, miR-126-3p, and miR-222-3p, were recently found to be enriched in circulating exosomes of patients with non-small cell lung cancers (NSCLCs). These miRNAs distinguished cancer cases from controls with high precision and were predicted to modulate the expression of genes within the oncogenic LINE-1 regulatory network. To test this hypothesis, plasma exosomes from controls, early, and late-stage NSCLC patients were co-cultured with non-tumorigenic lung epithelial cells for 72 h and processed for measurements of gene expression. Exosomes from late-stage NSCLC patients markedly increased the mRNA levels of LINE-1 ORF1 and ORF2, as well as the levels of target miRNAs in naïve recipient cells compared to saline or control exosomes. Late-stage exosomes also modulated the expression of oncogenic targets within the LINE-1 regulatory network, namely, ICAM1, AGL, RGS3, RGS13, VCAM1, and TGFβ1. In sharp contrast, exosomes from controls or early-stage NSCLC patients inhibited LINE-1 expression, along with many of the genetic targets within the LINE-1 regulatory network. Thus, late-stage NSCLC exosomes activate LINE-1 and miRNA-regulated oncogenic signaling in non-tumorigenic, recipient lung bronchial epithelial cells. These findings raise important questions regarding lung cancer progression and metastasis and open the door for the exploration of new therapeutic interventions. [ABSTRACT FROM AUTHOR] |
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