To examine the signaling pathways involved in MIR21 mimic-induced wound healing responses, western blot analysis was performed on wounded tissues on day 5 [PMC7053209]. Serum MIR21, CEA, NSE, and CYFRA21-1 levels were, on average, significantly higher in patients with NSCLC than in control individuals (Table 1) [PMC4737022]. However, serum MIR21 and CYFRA21-1 levels of NSCLC patients at TNM stages I-II were significantly lower than those of patients at TNM stages III-IV (t = 2.575, −2.301, resp [PMC4737022]. Comparison of joint detection of serum CYFRA21-1 and MIR21 levels with single detection of either marker indicated that AUC of single detection for CYFRA21-1, single detection for MIR21, and joint detection of both markers were 0.843, 0.872, and 0.909, respectively (Figure 1(c), Table 6) [PMC4737022]. Therefore, this study comparatively analyzed the value of MIR21 compared to tumor markers CEA, NSE, and CYFRA21-1 for early diagnosis of NSCLC [PMC4737022'>PMC4737022'>PMC4737022'>PMC4737022'>PMC4737022'>PMC4737022'>PMC4737022'>PMC4737022'>PMC4737022]. However, logistic multiple regression analysis indicated that early NSCLC (TNM stages I-II) was associated with serum CYFRA21-1 and MIR21 levels [PMC4737022]. Joint detection of MIR21 with serum CYFRA21-1 can further improve diagnostic efficiency for early NSCLC [PMC4737022]. The results indicated that occurrence of early NSCLC was significantly correlated with serum CYFRA21-1 (OR = 1.076; Wald χ 2 = 4.025) and MIR21 (OR = 2.473; Wald χ 2 = 9.153) levels (P < 0.05) (Table 5) [PMC4737022]. MIR21 had the highest diagnostic efficiency for early NSCLC (Figure 1(b), Table 4) [PMC4737022]. Therefore, MIR21 could serve as an important serum marker for auxiliary diagnosis of early NSCLC, while joint detection of serum MIR21 and CYFRA21-1 levels could improve diagnostic efficiency [PMC4737022]. This study indicates that, on average, serum MIR21 and CYFRA21-1 levels were lower in patients with NSCLC at TNM stages I-II than NSCLC at TNM stages III-IV [PMC4737022]. Serum MIR21, CEA, NSE, and CYFRA21-1 levels did not significantly differ with gender or age of NSCLC patients or with tumor pathology (Table 2) [PMC4737022]. AUC analysis showed that MIR21 had the highest diagnostic efficiency for early NSCLC [PMC4737022]. After removing the data for TNM stages III-IV, the AUC of using serum MIR21, CEA, NSE, and CYFRA21-1 levels to diagnose early NSCLC (TNM stages I-II) was 0.752, 0.806, 0.843, and 0.882, respectively [PMC4737022]. To validate the relationship between MIR21 expression and AUY922 sensitivity, we conducted a high-throughput compound screen in RKO cells that had been engineered to knock out the MIR21 locus (MIR21KO) and parental isogenic wild type (WT) cells.40 A number of HSP90 inhibitors produced a larger reduction in cell viability in MIR21KO cells in comparison with WT cells (Supplementary Figure 2A), with AUY922, 17-AAG, 17-DMAG, and ganetespib showing the highest activity [PMC5863695]. To validate the role of MIR21 in driving resistance to HSP90 inhibition, we infected MIR21KO DLD-1 cells with an inducible MIR21 or control (CTRL) viral vector (Supplementary Figure 2F) and monitored their response to AUY922 [PMC5863695]. A multiplex sandwich immunoassay showed a reduction in the level of HSP40 (