Characterization of miR-34a-Induced Epithelial-Mesenchymal Transition in Non-Small Lung Cancer Cells Focusing on p53

Background: Epithelial-mesenchymal transition (EMT), a phenotypic conversion of the epithelial to mesenchymal state, contributes to cancer progression. Currently, several microRNAs (miRNAs) are associated with EMT-mediated cancer progression, but the contribution of miR-34a to EMT in cancer cells remains controversial. The present study aimed to clarify the role of miR-34a in the EMT-related phenotypes of human non-small cell lung cancer (NSCLC) cell lines, A549 (p53 wild-type) and H1299 (p53-deficient). Methods: The miR-34a mimic and p53 small interfering RNA (siRNA) were transfected into the cells using Lipofectamine, and the obtained total RNA and cell lysates were used for real-time polymerase chain reaction and Western blotting analysis, respectively. Results: The introduction of the miR-34a mimic led to an increase in the mRNA and protein expression levels of alpha-smooth muscle actin (alpha-SMA), a mesenchymal marker gene, in A549, but not in H1299 cells. Additionally, miR-34a-induced the upregulation of p53 activity and migration was observed in A549, but not in H1299 cells. However, under the p53-knockdown condition, only alpha-SMA upregulation by miR-34a was abolished. Conclusion: These findings indicate a close relationship between p53 and miR-34a-induced EMT in p53-wild type NSCLC cells, which provides novel insights about the role of miR-34a in EMT-like phenotypic changes in NSCLC.

Automated summary

The study revealed that in p53-wild type NSCLC cells, miR-34a led to an upregulation of α-SMA, enhanced p53 activity, and promoted cell migration. However, these effects were not significant in p53-deficient cells. Under p53-knockdown condition, miR-34a only upregulated α-SMA, illustrating a close relationship between p53 and miR-34a-induced EMT in p53-wild type NSCLC cells.