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Tumor invasion and metastasis regulated by microRNA-184 and microRNA-574-5p in small-cell lung cancer.

ABSTRACT: Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor that has an extremely poor clinical prognosis. Metastasis is the key event in SCLC progression, but its mechanism has not been fully elucidated. MicroRNAs (miRNAs) have been proven to participate in cancer processes, but their function in SCLC has not been thoroughly studied either. Here, we performed microarray and quantitative real-time PCR (qRT-PCR) analyses to identify the miRNAs associated with metastasis and prognosis in SCLC as well as the correlation between serum and tissue. We also explored these miRNAs' promising molecular mechanisms by 3'UTR reporter assay and immunoblotting. We showed that miR-184 significantly attenuated the metastasis of SCLC, whereas miR-574-5p enhanced it. Both miRNAs were found to participate in ?-catenin signaling by suppressing protein tyrosine phosphatase receptor type U (PTPRU) or endothelial PAS domain protein 1 (EPAS1). Furthermore, miR-574-5p was verified as an independent prognostic risk factor for SCLC. Taken together, our findings provide a comprehensive analysis of the miRNA expression pattern in SCLC and indicate that miRNAs may serve as potential therapeutic and prognostic predictors in SCLC.

SUBMITTER: Zhou R

PROVIDER: S-EPMC4792579 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Tumor invasion and metastasis regulated by microRNA-184 and microRNA-574-5p in small-cell lung cancer.

Zhou Rui R Zhou Xiaoshu X Yin Zhongyuan Z Guo Jing J Hu Ting T Jiang Shun S Liu Li L Dong Xiaorong X Zhang Sheng S Wu Gang G

Oncotarget 20151201 42

Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor that has an extremely poor clinical prognosis. Metastasis is the key event in SCLC progression, but its mechanism has not been fully elucidated. MicroRNAs (miRNAs) have been proven to participate in cancer processes, but their function in SCLC has not been thoroughly studied either. Here, we performed microarray and quantitative real-time PCR (qRT-PCR) analyses to identify the miRNAs associated with metastasis and prognosi ...[more]

PMID: 26587830

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Project description:BACKGROUND:PM2.5 (particulate matter ≤ 2.5 μm) is one of the leading environmental risk factors for the global burden of disease. Whereas increasing evidence has linked the adverse roles of PM2.5 with cardiovascular and respiratory diseases, limited but growing emerging evidence suggests that PM2.5 exposure can affect the nervous system, causing neuroinflammation, synaptic dysfunction and cognitive deterioration. However, the molecular mechanisms underlying the synaptic and cognitive deficits elicited by PM2.5 exposure are largely unknown. METHODS:C57BL/6 mice received oropharyngeal aspiration of PM2.5 (1 and 5 mg/kg bw) every other day for 4 weeks. The mice were also stereotaxically injected with β-site amyloid precursor protein cleaving enzyme 1 (β-secretase, BACE1) shRNA or LV-miR-574-5p lentiviral constructs in the absence or presence of PM2.5 aspiration at 5 mg/kg bw every other day for 4 weeks. Spatial learning and memory were assessed with the Morris water maze test, and synaptic function integrity was evaluated with electrophysiological recordings of long-term potentiation (LTP) and immunoblot analyses of glutamate receptor subunit expression. The expression of α-secretase (ADAM10), BACE1, and γ-secretase (nicastrin) and the synthesis and accumulation of amyloid β (Aβ) were measured by immunoblot and enzyme-linked immunosorbent assay (ELISA). MicroRNA (miRNA) expression was screened with a microRNA microarray analysis and confirmed by real-time quantitative reverse transcription PCR (qRT-PCR) analysis. Dual-luciferase reporter gene and chromatin immunoprecipitation (ChIP) analyses were used to detect the binding of miR-574-5p in the 3'UTR of BACE1 and NF-κB p65 in the promoter of miR-574-5p, respectively. RESULTS:PM2.5 aspiration caused neuroinflammation and deteriorated synaptic function integrity and spatial learning and memory, and the effects were associated with the induction of BACE1. The action was mediated by NF-κB p65-regulated downregulation of miR-574-5p, which targets BACE1. Overexpression of miR-574-5p in the hippocampal region decreased BACE1 expression, restored synaptic function, and improved spatial memory and learning following PM2.5 exposure. CONCLUSIONS:Taken together, our findings reveal a novel molecular mechanism underlying impaired synaptic and cognitive function following exposure to PM2.5, suggesting that miR-574-5p is a potential intervention target for the prevention and treatment of PM2.5-induced neurological disorders.

Dataset Information

Tumor invasion and metastasis regulated by microRNA-184 and microRNA-574-5p in small-cell lung cancer.

Publications

Tumor invasion and metastasis regulated by microRNA-184 and microRNA-574-5p in small-cell lung cancer.

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