The results indicate that miR-4458 participated in the process of migration and EMT via directly targeting HMGA1 and miR-4458 might be a potential novel therapeutic target in NSCLC.
Collectively, the results of this study demonstrate that the TGFβ1-FOXM1-HMGA1-TGFβ1 positive feedback loop plays a crucial role in the cisplatin resistance of NSCLC by upregulating the expression of G6PD, providing a potential therapeutic target to restore chemosensitivity in cisplatin-resistant NSCLC.
Taken together, our findings indicate that the IL‑17/HMGA1/cyclin D1 axis plays an important role in NSCLC cell proliferation and may provide new insight into NSCLC pathogenesis and may thus aid in the development of novel therapeutic targets for NSCLC.
Using motif analysis to identify the CK2 core sub-network, we verified that elevated phosphorylation level of a CK2 substrate, HMGA1 was a critical node contributing to EGFR-TKI resistance in NSCLC cell.
Using immunohistochemistry, high levels of HMGA1 protein were positively correlated with the status of clinical stage (I-II vs. III-IV, P < 0.001), T classification (T1-T vs. T3-T4, P = 0.003), N classification (N0N1 vs. N2-N3, P < 0.001), M classification (M0 vs. M1, P = 0.002), and differentiated degree (high or middle vs. low or undifferentiated, P = 0.003) in NSCLC.
The miRNA-TF-miRNA interaction based molecular mechanisms of these seven markers in NSCLC revealed that HMGA1 and TFDP1 play vital roles in lung cancer tumorigenesis.
These results suggested that HMGA1 is a positive regulator of miR-222, and HMGA1 overexpression might contribute to dysregulation of Akt signaling in NSCLC.