MicroRNA‑433 reduces cell proliferation and invasion in non‑small cell lung cancer via directly targeting E2F transcription factor 3.

MOLECULAR MEDICINE REPORTS(2018)

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摘要
MicroRNAs (miRNA/miRs) have been associated with the initiation and progression of non-small-cell lung cancer (NSCLC). Hence, a comprehensive understanding of the association between dysregulated miRNAs and NSCLC may contribute to the identification of novel therapeutic methods for patients with NSCLC. MiRNA-433 (miR-433) has been reported to be dysregulated in numerous types of human cancers; however, its expression pattern, biological roles and associated mechanisms in NSCLC require further investigation. The present study aimed to detect miR-433 expression and determine its roles and underlying molecular mechanisms in NSCLC. In the present study, reverse transcription-quantitative polymerase chain reaction revealed that miR-433 was significantly downregulated in NSCLC tissues and cell lines. This decreased miR-433 expression was strongly associated with the tumor node metastasis stage and lymph node metastasis of patients with NSCLC. Cell Counting kit-8 and cell invasion assays revealed that the resumption of miR-433 expression decreased the proliferation and invasion of NSCLC cells. Bioinformatics analysis predicted E2F transcription factor 3 (E2F3) as a potential target of miR-433. Luciferase reporter assay, RT-qPCR and western blot analysis further demonstrated that E2F3 was a direct target of miR-433 in NSCLC. E2F3 downregulation induced by small interfering RNA exhibited inhibitory effects similar to those of miR-433 overexpression in NSCLC cells, and the restored E2F3 expression counteracted the suppressive effects on NSCLC cells induced by miR-433 overexpression. Therefore, niR-433 may inhibit the progression of NSCLC, at least in part, by targeting E2F3. The present study indicated that miR-433 may be investigated as an innovative candidate target for the therapy of patients with this fatal disease.
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microRNA-433,tumor suppressor,E2F transcription factor 3,non-small cell lung cancer
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