Abstract
Non-small cell lung cancer (NSCLC), one of the most common causes of cancer-related death, is a worldwide public health problem. MicroRNAs (miRNAs) have recently been identified as a novel class of regulators of carcinogenesis and tumor progression, including miRNAs associated with NSCLC. This study aimed to explore the role of miR-522 in NSCLC and the mechanisms underlying this role. We report here that miR-522 expression was significantly increased in both human NSCLC tissues and cell lines. Furthermore, an MTT assay, 5-Ethynyl-2′-deoxyuridine (EdU) assay kit and flow cytometry confirmed that the inhibition of miR-522 suppressed NSCLC cells proliferation and induced apoptosis. Compared with miR-522 overexpression, miR-522 inhibitor markedly reduced cells migration and invasion, as indicated by wound-healing and transwell assays. In addition, a luciferase assay identified DENN/MADD domain containing 2D (DENND2D) as a direct target of miR-522. qRT-PCR and western blot analyses indicated the reciprocal expression of miR-522 and DENND2D in NSCLC tissue samples. DENND2D was involved in miR-522 induced proliferation and metastasis of NSCLC cells by a miRNA-masking antisense oligonucleotides (miR-mask) technology. These data highlight a novel molecular interaction between miR-522 and DENND2D, which indicates that targeting miR-522 may constitute a potential therapy for NSCLC.
Highlights
Lung cancer is the leading cause of cancer mortality worldwide, and non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancer cases[1]
To study the expression and significance of miR-522 in NSCLC carcinogenesis, we measured the expression of miR-522 in 37 pairs of NSCLC tissues and their matched normal lung tissues using Quantitative real-time PCR (qRT-PCR). miR-522 was significantly upregulated in NSCLC tissues compared with their matched normal tissues (Fig. 1a)
To evaluate whether miR-522 inhibitor could induce apoptosis, we examined Annexin V-FITC/propidium iodide (PI) staining by flow cytometry
Summary
Lung cancer is the leading cause of cancer mortality worldwide, and non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancer cases[1]. In 2013, approximately 270,000 individuals were predicted to die of lung cancer in the European Union[2]. Recent technical developments have focused on identifying specific gene expression signatures that are associated with tumor staging and patient prognosis to improve prognosis and therapy. The DENN/MADD domain-containing (DENND) proteins regulate Rab GTPases and represent a newly recognized class of membrane trafficking proteins[4]. DENN/MADD domain containing 2D (DENND2D), a member of the DENND2 family, is located on chromosome 1p13.3 and encodes a 53-kDa protein that is a candidate tumor suppressor gene. Silencing via promoter hypermethylation regulates DENND2D in hepatocellular carcinoma (HCC)[7], esophageal squamous cell carcinoma (ESCC)[8] and gastric cancer (GC)[9]. The underlying mechanisms by which DENND2D is regulated require further exploration
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