MicroRNA-126 Inhibits Tumor Cell Growth and Its Expression Level Correlates with Poor Survival in Non-Small Cell Lung Cancer Patients

Background: It is controversial whether microRNA-126 is a tumor suppressive or oncogenic miRNA. More experiments are needed to determine whether microRNA-126 is associated with non-small cell lung cancer risk and prognosis. Methods: Over-expression of microRNA-126 was performed to evaluate the cell invasion and tumor growth in non-small cell lung cancer (NSCLC) cell lines and nude mouse xenograft model. Gain-of-function experiments and luciferase assays were performed to reveal the relationship between microRNA-126 and PI3K-Akt signal pathway in A549 cells. We analyzed the associations of the microRNA-126 expression between genetic variants within microRNA-126 and clinical information including smoking status, sex, age, and histological type and the tumor stage. Results: Over-expression of microRNA-126 in NSCLC cell lines decreased cell proliferation in vitro and tumor growth in the nude mouse xenograft model. And microRNA-126 repressed the activity of PI3K-Akt pathway by targeting binding sites in the 3'-untranslated region of PI3KR2 mRNA. The expression level of microRNA-126 was decreased in NSCLC lines and tumor tissues. The patients with low microRNA-126 expression had significantly poorer survival time than those with high microRNA-126 expression (means for survival time (month): 24.392 +/- 1.055 vs. 29.282 +/- 1.140, P = 0.005). However, there was no significant difference in the genotype and allele frequencies of the microRNA-126 variant (G>A, rs4636297) between cases and controls (P = 0.366). In addition, there was no association between SNP rs4636297 and survival time in NSCLC patients (P = 0.992). And microRNA-126 expression had no significant difference among the three genotype groups (P = 0.972). Conclusions: Our data indicate that microRNA-126 is a tumor-suppressor gene in NSCLC and low microRNA-126 expression is a unfavorable prognostic factor in NSCLC patients. However, the regulatory mechanism of microRNA-126 remains to be elucidated in different normal and malignant tissues. Therefore, further research is needed to explore the tumor suppressive functions of microRNA-126 in NSCLC.