An increasing number of studies have observed that microRNAs (miRNAs) are abnormally expressed in non-small cell lung cancer (NSCLC), and that their aberrant expression links with the progression and development of NSCLC. Therefore, it is necessary to full elucidate the specific roles of miRNAs in NSCLC, as this may facilitate the identification of novel therapeutic targets. In the present study, it was observed that miRNA-598 (miR-598) expression was significantly downregulated in NSCLC tissues and cell lines. Decreased miR-598 was negatively correlated with TNM stage and lymph node metastasis in NSCLC patients. In addition, ectopic expression of miR-598 reduced NSCLC cell proliferation and invasion in vitro. The zinc finger E-box-binding homeobox 2 (ZEB2) was validated as a direct target of miR-598 in NSCLC cells. ZEB2 was upregulated in NSCLC tissues and the upregulation of ZEB2 was inversely correlated with the miR-598 level. The results revealed that restored ZEB2 expression abrogated the inhibitory effects of miR-598 overexpression in NSCLC cells. In conclusion, the results of the present study revealed that miR-598 may inhibit the progression of NSCLC by directly targeting ZEB2, which suggests that this miRNA may be identified as a potential novel prognostic biomarker and therapeutic target for patients with NSCLC.
The role of the majority of long noncoding RNAs (lncRNAs) in the progression of nonsmall-cell lung cancer (NSCLC) remains elusive, despite their potential value, thus warranting in-depth studies. For example, detailed functions of the lncRNA POU6F2 antisense RNA 2 (POU6F2-AS2) in NSCLC are unknown. Herein, we investigated the expression status of POU6F2-AS2 in NSCLC. Furthermore, we systematically delineated the biological roles of POU6F2-AS2 in NSCLC alongside its downstream molecular events. We measured the expression levels of POU6F2-AS2 using quantitative real-time polymerase chain reaction and performed a series of functional experiments to address its regulatory effects in NSCLC cells. Using bioinformatic platforms, RNA immunoprecipitation, luciferase reporter assays, and rescue experiments, we investigated the potential mechanisms of POU6F2-AS2 in NSCLC. Subsequently, we confirmed the remarkable overexpression of POU6F2-AS2 in NSCLC using The Cancer Genome Atlas database and our own cohort. Functionally, inhibiting POU6F2-AS2 decreased NSCLC cell proliferation, colony formation, and motility, whereas POU6F2-AS2 overexpression exhibited contrasting effects. Mechanistically, POU6F2-AS2 acts as an endogenous decoy for microRNA-125b-5p (miR-125b-5p) in NSCLC that causes the overexpression of the E2F transcription factor 3 (E2F3). Moreover, suppressing miR-125b-5p or increasing E2F3 expression levels sufficiently recovered the anticarcinostatic activities in NSCLC induced by POU6F2-AS2 silencing. Thus, POU6F2-AS2 aggravates the oncogenicity of NSCLC by targeting the miR-125b-5p/E2F3 axis. Our findings suggest that POU6F2-AS2 is a novel therapeutic target for NSCLC.
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