MiRNA-488-3p inhibits malignant progression of NSCLC by modulating ADAM9.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiRNA-488-3p inhibits malignant progression of NSCLC by modulating ADAM9, by Y. Wu, Y. Wu, X.-Y. Chen, Y.-X. Niu, F.-Z. Lv, W. Gao, published in Eur Rev Med Pharmacol Sci 2020; 24 (17): 8893-8901-DOI: 10.26355/eurrev_202009_22830-PMID: 32964979" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/22830.

MiRNA-488-3p inhibits malignant progression of NSCLC by modulating ADAM9.

OBJECTIVE: The purpose of this study was to investigate the role of microRNA-488-3p in the proliferation, invasion and migration of lung cancer cells and to further explore the potential regulatory mechanisms. PATIENTS AND METHODS: MicroRNA-488-3p expression in 46 pairs of tumor tissue and paracancerous tissue specimens collected from non-small cell lung cancer (NSCLC) patients were measured through quantitative real-time polymerase chain reaction (qRT-PCR) method, and the interplay between microRNA-488-3p expression and some clinical indicators of these subjects was also analyzed. In addition, microRNA-488-3p overexpression models were constructed in NSCLC cell lines, and then Cell Counting Kit-8 (CCK-8) test and transwell assays were carried out to evaluate the effect of microRNA-488-3p on the NSCLC cell functions. Furthermore, bioinformatics analysis and luciferase reporter gene assay were carried out to uncover the potential interaction between microRNA-488-3p and its downstream gene ADAM9. RESULTS: QPCR results revealed that microRNA-488-3p showed a significant lower expression in NSCLC tissue samples than in adjacent normal ones. In comparison to patients with high expression of microRNA-488-3, patients with low expression of microRNA-488-3 exhibited higher incidence of lymph node or distant metastasis and lower survival rate. In vitro cell experiments showed that, in comparison to control group, overexpression of microRNA-488-3p significantly weakened the proliferation ability as well as the invasion and migration of NSCLC cells. Subsequently, a significant increase in ADAM9 expression in NSCLC tissue samples was found, which indicated its negative correlation with microRNA-488-3p. In addition, cell recovery experiment demonstrated that overexpression of ADAM9 could counteract the impact of microRNA-488-3p upregulation on the proliferation and invasion ability of NSCLC cells, and the two may thus together affect the malignant progression of NSCLC. CONCLUSIONS: It can be concluded that microRNA-488-3p, which is associated with the incidence of metastasis in NSCLC patients, can inhibit the malignant progression of NSCLC cells by modulating ADAM9 expression.

Knockdown of MMP12 inhibits the growth and invasion of lung adenocarcinoma cells.

Matrix metalloproteinase-12 (MMP12) is involved in many pathological processes including cancer. The expression and function of MMP12 in lung adenocarcinoma (LAC) remain unclear. The present study aimed to investigate the correlation of MMP12 expression with LAC patients and clarify its role in growth and invasion of LAC cells. The expression of MMP12 in human LAC was examined by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was used for observing the effects of lentiviral vector-mediated MMP12 shRNA (shMMP12) on cell growth and invasion in LAC cell lines (A549), indicated by MTT and Transwell assays. We found that the expression of MMP12 protein was significantly increased in LAC tissues compared with that in adjacent non-cancerous tissues (ANCT) (57.69% vs. 32.69%, P = 0.019), and was closely correlated with the pathological stage and lymph node metastasis of LAC patients (P = 0.01; P = 0.003). Knockdown of MMP12 inhibited proliferation and invasion of LAC cells followed by the downregulation of proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF). In conclusion, our findings show that high expression of MMP12 is correlated with the pathological stage and tumor metastasis of LAC patients, and knockdown of MMP12 suppresses the development of LAC cells, suggesting that MMP12 may be a promising therapeutic target for the treatment of LAC.

Over-expressing CYLD augments antitumor activity of TRAIL by inhibiting the NF-κB survival signaling in lung cancer cells.

The death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in tumor cells. But studies have demonstrated that many tumor cells were resistant to TRAIL-induced apoptosis. CYLD is recognized as a negative regulator of nuclear factor-kappa B(NF-κB) activity. To explore a correlation between CYLD expression and responsiveness to TRAIL in lung cancer cell lines, we established lung cancer cell lines that stably express CYLD. Our data provided the first evidence that increased expression of CYLD directly blocks TRAIL-induced NF-κB activation, and consequently increases TRAIL-induced apoptosis in lung cancer cells. CYLD may act as a therapeutic target of lung cancer. Targeting CYLD, in combination with TRAIL, may be a new strategy to treat lung cancer with high NF-κB activity.