MiR-367-3p Regulates Cells Proliferation and Invasion in NSCLC by Targeting ZEB2

Abstract

microRNAs play an important role in the development and biological phenotype of lung cancer. The present study was to investigate miR-367-3p level in non-small cell lung cancer (NSCLC) patients and its biological function of NSCLC cells. Twenty-two patients with NSCLC (13 cases of adenocarcinoma and 9 cases of squamous carcinoma) admitted to our hospital and treated by surgery were included. During the operation, cancer tissue, paracancerous tissue and 5 mL peripheral blood were collected. Meanwhile, 22 healthy controls were selected and 5 mL peripheral blood was taken. Real-time PCR was applied to detected the expression of miR-367-3p in cancer tissues, peripheral blood of patients with NSCLC and healthy controls. miR-367-3p was detected in lung cancer cell lines (A549) and normal bronchial epithelial cells (BEAS-2B). The proliferation and invasion ability of A549 cells before and after infection were detected by MTT and Transwell assay after transfection with exogenous miR-367-3p. The downstream target gene of miR-367-3p was analyzed by bioinformatics. Zinc finger E-box binding homeobox 2 (ZEB2) was detected by Real-time PCR and Western blot. miR-367-3p in cancer tissues of 22 NSCLC patients was lower than corresponding normal tissues (P<0.05), and the serum miR-367-3p level in healthy subjects was higher than NSCLC subjects (P<0.05). The area under the receiver operating characteristic (ROC) curve of NSCLC was 0.95 (95%CI: 0.89-1.00) and 0.85 (95%CI: 0.74-0.97) respectively; The proliferation and migration ability of lung cancer cell line A549 transfected with exogenous miR-367-3p decreased significantly (P<0.05); Bioinformatics predicted that the downstream target of miR-367-3p was ZEB2 and up-regulating miR-367-3p expression, ZEB2 gene was decreased (P<0.05). The Cancer Genome Atlas (TCGA) data analysis showed that there was no significant difference in overall survival (OS) and disease free survival (DFS) between ZEB2 high expression group and low expression group (P>0.05). ZEB2 expression was positively correlated with infiltration of B lymphocytes (r=0.32, P<005), CD8⁺ T cells (r=0.44, P<005), CD4⁺ T cells (r=0.46, P<005), macrophages (r=0.65, P<005), neutrophils (r=0.73, P<005) and dendritic cells (r=0.71, P<005) in NSCLC. The expression of miR-367-3p is down regulated in NSCLC patients and participates in the biological process of proliferation and invasion of NSCLC by targeting ZEB2 gene.