The interaction between ΔNp63α and TAp63α, mediated by miR-205-5p, inhibits the migration of lung adenocarcinoma cells

Lung cancer is a highly lethal disease worldwide, resulting from a combination of genetic, epigenetic, and environmental factors. The amplification of specific chromosomal regions is a hallmark of cancer progression; for instance, the 3q region of chromosome 3 is notably amplified in lung cancer, contributing to early tumor development. TP63, a member of the p53 family, is located in the 3q region. The presence of two distinct sets of TP63 isoforms (ΔNp63 and TAp63) complicates its functional role. Furthermore, miR-205-5p, a crucial player in cancer progression, has a predicted target site in the 5'-untranslated region (5'-UTR) of TAp63 transcripts. To investigate a potential correlation between miR-205-5p and the ΔNp63 and TAp63 isoforms, we conducted an in silico study followed by experimental validations on clinical tissue samples. We found a significant positive correlation between the expression of miR-205-5p and both isoforms of TP63 in lung adenocarcinoma (LUAD) datasets. The correlation between ΔNp63 and miR-205-5p was further confirmed in tissue samples from LUAD patients. Subsequently, we overexpressed ΔNp63α in lung adenocarcinoma cell lines and observed an upregulation of miR-205-5p, TAp63α, and DICER in the A549 cell line. Overexpression of ΔNp63α also inhibited the migration of A549 cells by reducing epithelial-mesenchymal transition (EMT) markers and increasing mesenchymal-epithelial transition (MET) markers. We conducted a luciferase assay to investigate the direct interaction between miR-205-5p and the 5'-UTR of TAp63 and observed a positive association. Overexpression of miR-205-5p in the A549 cell line led to the upregulation of TAp63α and DICER. Additionally, we found a reduction in migration following miR-205-5p transfection. Based on these results, it appears that there is a ΔNp63α/miR-205-5p/TAp63α/DICER axis involved in the regulation of migration in lung adenocarcinoma, which is cell-specific.