OBJECTIVE: The aim of this paper is to investigate the functions of long noncoding RNA (lncRNA) FOXF1 Adjacent Non-Coding Developmental Regulatory RNA (FENDRR) in the growth and aggressiveness of non-small cell lung cancer (NSCLC).
PATIENTS AND METHODS: The expression of FENDRR in NSCLC tissues and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and colony formation assays were conducted to explore the roles of FENDRR on the growth of NSCLC cell. The wound healing and transwell invasion assays were conducted to explore the impact of FENDRR on NSCLC cell migration and invasion. The apoptosis of NSCLC cell was detected using flow cytometer-based Annexin V/Propidium Iodide (PI) dual staining. The xenograft model was conducted to investigate the effect of FENDRR on the growth of NSCLC cell in vivo. The expression of Ki67 was measured by immunohistochemical (IHC) staining using Ki67 antibody. Bioinformatics analysis and Luciferase reporter assay were applied to identify that miR-761 was the target of FENDRR. Additional, colony formation and transwell experiments were utilized to confirm that FENDRR inhibited the growth and aggressiveness of NSCLC cell by regulating miR-761.
RESULTS: We found a marked down-regulation of FENDRR in NSCLC tissues compared to tumor-adjacent tissues. FENDRR down-expression was detected in four NSCLC cell lines (H1650, HCC827, H1975 and A549) compared to the human non-tumorigenic bronchial epithelial cell, BEAS-2B. Low expression of FENDRR was identified as a predictive factor for poor prognosis of patients with NSCLC. The over-regulation of FENDRR inhibited the proliferation, migration and invasion capacities of NSCLC cell and promoted the apoptosis of NSCLC cell in vitro whereas the down-regulation of FENDRR caused the opposite results. Moreover, the over-expression of FENDRR restrained the growth of NSCLC cell in vivo. We found that there were potential binding sites between FENDRR and miR-761 and the level of miR-761 was inversely associated with the expression of ENDRR in NSCLC tissues. Finally, the rescue experiments suggested that the anti-oncogenic role of FENDRR was at least partially mediated by miR-761 in NSCLC.
CONCLUSIONS: We found that FENDRR was down-expressed in NSCLC and the over-expression of FENDRR inhibited the malignant phenotypes of NSCLC cell by binding to miR-761 competitively.Free PDF Download
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To cite this article
M.-Y. Zhang, Z.-L. Zhang, H.-X. Cui, R.-K. Wang, L. Fu
Long non-coding RNA FENDRR inhibits NSCLC cell growth and aggressiveness by sponging miR-761
Eur Rev Med Pharmacol Sci
Vol. 22 - N. 23