Abstract
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 α-smooth muscle actin (α-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 α-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.
Highlights
MicroRNAs are a class of non-coding RNAs that function as master regulators of the genome by modulating the expression of tens to hundreds of genes and controlling several cellular pathways at once
We have demonstrated that several miRNAs are associated with certain drug-induced Epithelial–mesenchymal transition (EMT) in alveolar epithelial cell lines derived from humans and rats [9,10,11,12], which assumes that serious lung injury triggered by the drugs is linked with the conversion of epithelial to mesenchymal state in the cells through the EMT process
The miR-34a mimic significantly increased the apoptosis ratio of A549 cells at 24 and 72 h, whereas miR-34a-induced apoptosis in H1299 cells was less observed compared with that in A549 cells (Figure 1B,C). These findings suggest that the p53-miR-34a axis contributes to apoptosis induction and work in A549 cells, but not in H1299 cells, as expected
Summary
MicroRNAs (miRNAs) are a class of non-coding RNAs that function as master regulators of the genome by modulating the expression of tens to hundreds of genes and controlling several cellular pathways at once. 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 miR34a in the EMT-related phenotypes of human non-small cell lung cancer (NSCLC) cell lines, A549. Results: The introduction of the miR-34a mimic led to an increase in the mRNA and protein expression levels of α-smooth muscle actin (α-SMA), a mesenchymal marker gene, in A549, but not in H1299 cells. 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
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
