Dataset Information

Suppression of non-small cell lung cancer migration and invasion by hsa-miR-486-5p via the TGF-?/SMAD2 signaling pathway.

ABSTRACT: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. SMAD family member 2 (SMAD2) is a key element downstream of the transforming growth factor beta (TGF-?) signaling pathway that regulates cancer metastasis by promoting the epithelial-mesenchyme transition (EMT). MicroRNA miR-486-5p is a tumor suppressor in NSCLC progression. However, it remains unclear whether miR-486-5p is implicated in TGF-? signaling and EMT in NSCLC. In the present study, high expression of SMAD2 mRNA was detected in NSCLC tissues and cell lines, and was associated with poor survival of patients with NSCLC. By contrast, miR-486-5p was downregulated in NSCLC tissues and cell lines. In silico prediction showed that SMAD2 was a potential target of miR-486-5p. The prediction was verified using a dual-luciferase reporter assay. Transwell assays showed that knockdown of SMAD2 inhibited TGF-?-induced EMT and migration and invasion in NSCLC cells. Similarly, miR-486-5p overexpression suppressed TGF-?-induced EMT and migration and invasion of NSCLC cells. The present study provides a new insight into the role of miR-486-5p in regulating TGF-?-mediated EMT and invasion in NSCLC.

SUBMITTER: Chen T

PROVIDER: S-EPMC6856587 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Suppression of non-small cell lung cancer migration and invasion by hsa-miR-486-5p via the TGF-β/SMAD2 signaling pathway.

Chen Tao T Zhu Jianjie J Cai Tingting T Du Wenwen W Zhang Yang Y Zhu Qingqing Q Liu Zeyi Z Huang Jian-An JA

Journal of Cancer 20191015 24

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. SMAD family member 2 (SMAD2) is a key element downstream of the transforming growth factor beta (TGF-β) signaling pathway that regulates cancer metastasis by promoting the epithelial-mesenchyme transition (EMT). MicroRNA miR-486-5p is a tumor suppressor in NSCLC progression. However, it remains unclear whether miR-486-5p is implicated in TGF-β signaling and EMT in NSCLC. In the present study, high expressi ...[more]

PMID: 31762811

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Project description:BackgroundFetal growth restriction (FGR) is a worldwide problem, and a major cause of perinatal morbidity. The precise molecular mechanisms involved in placental development and function during FGR remain poorly understood. Circular RNAs (circRNAs) are important biological molecules associated with disease pathogenesis. However, the role of circRNAs in FGR has not been well studied.MethodscircRNA expression profiles in placental tissues with and without FGR were identified by circRNA microarray. circRNA expression was verified by quantitative reverse-transcription PCR (RT-qPCR) assay. The effect of hsa_circ_0000848 and hsa-miR-6768-5p on HTR-8 cell apoptosis, migration, and invasion was evaluated. The association between hsa_circ_0000848 and hsa-miR-6768-5p was confirmed by dual luciferase activity and anti-AGO2 RNA immunoprecipitation (RIP) assays. Protein levels were examined via western blotting.ResultsRT-qPCR results showed that hsa_circ_0000848 expression was significantly down-regulated in FGR placenta. Hsa_circ_0000848 overexpression and hsa-miR-6768-5p inhibitor suppressed apoptosis, and promoted cell migration and invasion. In addition, hsa_circ_0000848 overexpression and hsa-miR-6768-5p inhibitor increased the protein abundance of BCL2, MMP2 and MMP9, and decreased the protein abundance of cleaved caspase-3, cleaved caspase-9, and BAX, whereas hsa_circ_0000848 knockdown caused the opposite effect. Moreover, a significant increase in hsa-miR-6768-5p expression and a negative correlation between hsa_circ_0000848 and hsa-miR-6768-5p were identified in the FGR tissues. Luciferase reporter and RIP assay results revealed binding of hsa-miR-6768-5p to hsa_circ_0000848. Furthermore, hsa-miR-6768-5p overexpression eliminated the effect of hsa_circ_0000848 overexpression in HTR-8 cells.Conclusionshsa_circ_0000848 expression is significantly down-regulated in the FGR placenta. hsa_circ_0000848 promotes trophoblast cell migration and invasion, and inhibits cell apoptosis via the sponging of hsa-miR-6768-5p. Our study provided a novel insight into mechanisms underlying the pathogenesis of FGR, as well as into new strategies for the treatment of FGR.

Project description:BackgroundTwo mature microRNAs (miRNAs), hsa-miR-125a-3p and hsa-miR-125a-5p (collectively referred to as hsa-miR-125a-3p/5p), are derived from 3' and 5' ends of pre-miR-125a, respectively. Although impaired regulation of hsa-miR-125a-5p has been observed in some tumors, the role of this miRNA in invasion and metastasis remains unclear, and few studies have examined the function of hsa-miR-125a-3p. In order to characterize the functions of hsa-miR-125a-3p/5p in invasion and metastasis of non-small cell lung cancer (NSCLC), we investigated the relationships between hsa-miR-125a-3p/5p expression and lymph node metastasis in NSCLC tissues. We also explored the impact of expression of these miRNAs on invasive and migratory capabilities of lung cancer cells.MethodsExpression of hsa-miR-125a-3p/5p in NSCLC tissues was explored using real-time PCR. The relationships between hsa-miR-125a-3p/5p expression and pathological stage or lymph node metastasis were assessed using the Spearman correlation test. For in vitro studies, lung cancer cells were transfected with sense and antisense 2'-O-methyl oligonucleotides for gain-of-function and loss-of-function experiments. Transwell experiments were performed to evaluate cellular migration and invasion.ResultsExpression of hsa-miR-125a-3p/5p was lower in NSCLC tissues than in adjacent normal lung tissues (LAC). Furthermore, the results from the Spearman correlation test showed a negative relationship between hsa-miR-125a-3p expression and pathological stage or lymph node metastasis and an inverse relationship between hsa-miR-125a-5p expression and pathological stage or lymph node metastasis. In vitro gain-of-function experiments indicated that hsa-miR-125a-3p and hsa-miR-125a-5p function in an opposing manner, suppressing or enhancing cell migration and invasion in A549 and SPC-A-1 cell lines, respectively. These opposing functions were further validated by suppression of hsa-miR-125a-3p and hsa-miR-125a-5p expression in loss-of-function experiments.ConclusionHsa-miR-125a-3p and hsa-miR-125a-5p play distinct roles in regulation of invasive and metastatic capabilities of lung cancer cells, consistent with the opposing correlations between the expression of these miRNAs and lymph node metastasis in NSCLC. These results provide new insights into the roles of miR-125a family members in the development of NSCLC.

Dataset Information

Suppression of non-small cell lung cancer migration and invasion by hsa-miR-486-5p via the TGF-?/SMAD2 signaling pathway.

Publications

Suppression of non-small cell lung cancer migration and invasion by hsa-miR-486-5p via the TGF-β/SMAD2 signaling pathway.

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