ABSTRACT
Non-small cell lung cancer (NSCLC) is an aggressive malignancy with increasing worldwide incidence and is characterized by dismal prognosis due to its early recurrence and metastasis. Accumulating evidence documented that aberrantly expressed circular RNAs (circRNAs) are critically involved in tumorigenesis. In the current study, we focused on a novel circRNA, circ_0016760 in NSCLC. qRT-PCR was carried out to determine the expression level of circ_0016760 in tissue samples and cell lines. The clinical value of circ_0016760 was also investigated. The functions of circ_0016760 was explored by CCK-8, colony formation, flow cytometry, Transwell and animal experiments. Luciferase reporter assays were conducted to investigate the association between circ_0016760 and miR-1287 and miR-1287 and GAGE1. We found that circ_0016760 was enhanced in NSCLC tissues and cells and the upregulation of circ_0016760 is associated with advanced TNM stages, lymph node metastasis and adverse prognosis in NSCLC patients. Moreover, circ_0016760 could significantly promote cell growth and metastatic properties and inhibit cell apoptosis in NSCLC cells. In mechanism, circ_0016760 functioned as a sponge for miR-1287 and regulated the expression of GAGE1. Subsequently, functional assays illustrated that the oncogenic properties of circ_0016760 is partly attribute to the regulation of miR-1287/GAGE1 axis. In summary, circ_0016760/miR-1287/GAGE1 signaling might play vital roles in the tumorigenesis and progression of NSCLC.
Subject(s)
Antigens, Neoplasm/metabolism , Carcinoma, Non-Small-Cell Lung/metabolism , Lung Neoplasms/metabolism , MicroRNAs/metabolism , Neoplasm Proteins/metabolism , RNA/metabolism , Up-Regulation , Animals , Antigens, Neoplasm/genetics , Apoptosis , Carcinoma, Non-Small-Cell Lung/diagnosis , Cell Line , Cell Movement , Cell Proliferation , Female , Humans , Lung Neoplasms/diagnosis , Male , Mice , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/genetics , Middle Aged , Neoplasm Proteins/genetics , Neoplasms, Experimental/diagnosis , Neoplasms, Experimental/metabolism , Prognosis , RNA/genetics , RNA, CircularABSTRACT
MicroRNAs (miRs) function as key regulators of gene expression and their deregulation is associated with the carcinogenesis of various cancers. In the present study, we investigated the biological role and mechanism of miR-361-5p in colorectal carcinoma (CRC) and gastric cancer (GC). We showed that microRNA-361-5p (miR-361-5p) was down-regulated in CRC and GC in comparison to the controls. Meanwhile, the expression levels of miR-361-5p negatively correlated with lung metastasis and prognosis in clinical CRC patients. Overexpression of miR-361-5p markedly suppressed proliferation, migration and invasion of cancer cells. Additionally, this phenotype could be partially rescued by the ectopic expression of staphylococcal nuclease domain containing-1 (SND1). SND1 was identified as a target of miR-361-5p using bioinformatics analysis and in vitro luciferase reporter assays. In turn, SND1 bound to pre-miR-361-5p and suppressed the expression of miR-361-5p, thus exerting a feedback loop. Most interestingly, in vivo studies showed that restoration of miR-361-5p significantly inhibited tumor growth and especially the lung metastasis in nude mice. Therefore, it could be concluded that miR-361-5p functions as a tumor-suppressive miRNA through directly binding to SND1, highlighting its potential as a novel agent for the treatment of patients with CRC and GC.
