RECK and Bcl-2. Our results were consistent with previous reports which demonstrated that upregulation of miR-21 and decrease of PTEN and RECK as well as increase of Bcl-2 occur in YTMLC-90 and NCI-H157 cell lines. Our studies also showed that down-regulation of miR-21 could lead to a significant increase in PTEN and RECK and a significant decrease in Bcl-2 at both mRNA and protein level. Furthermore, our findings revealed down-regulation of miR-21 suppressed the proliferation of NSCLC cells, suggesting that miR-21 as direct regulator of PTEN, RECK and Bcl-2 could be the key factor Rapamycin involved in cell proliferation in NSCLC. Interestingly, our data outline negative regulation of PTEN and RECK, but positive regulation of Bcl-2 by miR-21 in cell proliferation. The exact mechanism of how it occurs needs to be further studied. Results of our current study have also highlighted the importance of up-regulation of miR-21 for NSCLC cells to develop and/or sustain the invasive phenotype. The decrease in miR-21 expression level leads to the enhanced induction of PTEN and RECK, but the reduced expression of Bcl-2 which could further promote cell migration and invasion in NCSLC cells. Our flow cytometry data demonstrated that miR-21 silencing could induce apoptosis which was positively correlated with Bcl-2, but negatively correlated with PTEN and RECK in NSCLC cells. Furthermore, our results indicated an association between the induction of the cell cycle arrest at G2/M phase and PTEN gene expression regulated by miR-21 silencing. These results were in agreement with previous reports that PTEN is a regulator of the cell cycle. Taken together, we have not observed any change in the levels of miR-21 and its target genes both in YTMLC-90 and NCI-H157 cells suggesting that similar regulatory mechanisms of between miR-21 and its target genes involved in cell proliferation, viability, invasion, migration and apoptosis occur in GSQCLC as well as NSCLC. In summary, the results of this study further showed the regulatory mechanism of miR-21 targeting PTEN, RECK and Bcl-2 in NSCLC. In particular, our findings revealed that miR-21 promoted the progression of GSQCLC through negative regulation of PTEN and RECK, but positive regulation of Bcl-2. We propose that the molecular mechanisms that miR-21 promotes cell proliferation, viability, invasion, and apoptosis via its target genes are common both in GSQCLC and other NSCLC. The possible regulatory mechanism of miR-21 can be showed in Fig. 9.