Abstract
Dysregulated expression profiles of microRNAs (miRNAs) have been observed in several types of cancer, including non-small cell lung cancer (NSCLC); however, the diagnostic and prognostic potential of circulating miRNAs in NSCLC remains largely undefined. Here we found that circulating miR-320a was significantly down-regulated (~5.87-fold; p < 0.0001) in NSCLC patients (n = 80) compared to matched control plasma samples from healthy subjects (n = 80). Kaplan-Meier survival analysis revealed that NSCLC patients with lower levels of circulating miR-320a had overall poorer prognosis and survival rates compared to patients with higher levels (p < 0.0001). Moreover, the diagnostic and prognostic potential of miR-320a correlated with clinicopathological characteristics such as tumor size, tumor node metastasis (TNM) stage, and lymph node metastasis. Functionally, depletion of miR-320a in human A549 lung adenocarcinoma cells induced their metastatic potential and reduced apoptosis, which was reversed by exogenous re-expression of miR-320a mimics, indicating that miR-320a has a tumor-suppressive role in NSCLC. These results were further supported by high levels of epithelial-mesenchymal transition (EMT) marker proteins (e.g., Beta-catenin, MMP9, and E-cadherin) in lung cancer cells and tissues via immunoblot and immunohistochemistry experiments. Moreover, through bioinformatics and dual-luciferase reporter assays, we demonstrated that AKT3 was a direct target of miR-320a. In addition, AKT3-associated PI3K/AKT/mTOR protein-signaling pathways were elevated with down-regulated miR-320a levels in NSCLC. These composite data indicate that circulating miR-320a may function as a tumor-suppressor miRNA with potential as a prognostic marker for NSCLC patients.
Highlights
Despite recent advancements in the diagnosis, prognosis, and treatment of non-small cell lung cancer (NSCLC), the 5-year survival rate is unacceptable at
Because miR-320a showed a significant down-regulation in NSCLC patients compared to the healthy controls, we evaluated any potential associations of its down-regulated levels with NSCLC patients’ prognosis
When we evaluated NSCLC stages, patients with tumor node metastasis (TNM) stage II cancer showed an ∼5-fold down-regulation (n = 19; p < 0.0001; 95% CI: 14.59–34.54), stage III patients showed an ∼7-fold down-regulation (n = 54; p < 0.0001; 95% CI: 20.47–32.05), and stage IV patients showed an ∼4-fold downregulation (n = 7; p < 0.005; 95% CI: 6.91–38.83) relative to healthy controls
Summary
Despite recent advancements in the diagnosis, prognosis, and treatment of non-small cell lung cancer (NSCLC), the 5-year survival rate is unacceptable at
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
