Survival analyses of 19 DEMs in the DEM‑DEG regulatory network and 36 DEGs in the PPI network module revealed that 34 DEGs (including TOP2A, CCNB1, BIRC5, and TTK) and two miRNAs (miR‑21‑5p and miR‑31‑5p) were significantly associated with NSCLC prognosis.
Extracellular vesicles secreted by hypoxia pre-challenged mesenchymal stem cells promote non-small cell lung cancer cell growth and mobility as well as macrophage M2 polarization via miR-21-5p delivery.
Using different NSCLC cell lines, we demonstrated that OAT promoted the proliferation, invasion, and migration, inhibited the apoptosis, and altered cell cycle of NSCLC cells; besides, the involvement of OAT-miR-21-glycogen synthase kinase-3β signaling in the functional role of OAT in NSCLC was also revealed.
The expression of miR-21 in tumor cell lines and clinical NSCLC tumor samples was positively correlated with hypoxia-inducible factor-1α and negatively correlated with PTEN.
Notably, a growing body of evidence further shows that miR-21 is closely associated with the prognosis prediction, recurrence and diagnosis of cancer patients, indicating that miR-21 may be a novel promising biomarker for the diagnosis and prognosis prediction of NSCLC.
We demonstrated that the miR-21 inhibitor induced apoptosis through inhibiting the PI3K/Akt/NF-κB signaling pathway in non-small cell lung carcinoma (NSCLC).
When applied for NSCLC diagnosis, combined application of miR-21 and let-7a had a sensitivity of 0.790, specificity of 0.750, which is significantly higher than application alone of miR-21(sensitivity 0.647; specificity 0.641), let-7a (sensitivity 0.653; specificity 0.718) or computed tomography-guided core-needle biopsy (CTCB) (sensitivity 0.725; specificity 0.609) (P < .01).
Therapeutic modulation of miR-21 by use of antisense sequences entrapped in different delivery systems has shown promising results in impairment of NSCLC.
These subgroup analyses also highlighted that elevated expression of miR-21 and miR-155 and low levels of expression of miR-148a, miR-148b, and miR-<i>let</i>-7 were associated with poor prognosis in NSCLC.
In summary, our study defines that miR-30c and miR-21 may be valid biomarkers for early NSCLC detection and their silencing could be beneficial for therapeutic applications.
Cox regression analysis revealed that miR-21-5p (hazard ratio [HR]: 1.616, 95% CI: 1.114-2.342, p = 0.011) and miR-30d-5p (HR: 0.578, 95% CI: 0.400-0.835, p = 0.003) were independent prognostic factors in NSCLC for overall survival.
Mechanistically, fructose-1,6-biphosphatase (FBP1) was a direct target of miR-21 and observed a negative correlation between miR-21 and FBP1 in NSCLC samples.