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LncRNA SNHG5 suppresses cell migration and invasion of human lung adenocarcinoma via regulation of epithelial-mesenchymal transition

ABSTRACT: Long noncoding RNAs (lncRNAs) are emerging as important regulators in cellular processes. In the present study, the effects of the long non-coding RNA, SNHG5 was investigated in lung adenocarcinoma (LAD) and we also revealed the underlying mechanisms of it. Overexpressed SNHG5 suppressed migration and invasion of LAD cell line A549 in vitro. Transcriptome sequencing analysis supported the inhibitory effects of SNHG5 were associated with cell adhesion molecules. In addition, western blot and immunofluorescence showed that the expression of SNHG5 was associated with epithelial-mesenchymal transition (EMT) markers. Furthermore, we determined the effects of SNHG5 in EMT procession of A549 induced by TGF-β1. Consistent with previous results, overexpression of SNHG5 suppressed the migration and invasion, and also the expression of EMT-related transcription factors including Snail, SLUG and ZEB1 in EMT of A549 reduced by TGF-β1. Moreover, qRT-PCR demonstrated expression of SNHG5 was positively correlated with E-cadherin protein expression, but negatively correlated with N-cadherin and Vimentin in LAD tissues. In summary, our study demonstrated that lncRNA SNHG5 could suppress cell migration and invasion of LAD cancer by inhibiting EMT procession, highlighting the potential of SNHG5 as a therapy strategy for lung adenocarcinoma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE143766 | GEO | 2020/01/17

REPOSITORIES: GEO

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Project description:Epithelial-mesenchymal transition (EMT) has recently been recognized as a key element of cell invasion, migration, metastasis, and drug resistance in several types of cancer, including non-small cell lung cancer (NSCLC). Our aim was to clarify microRNA (miRNA) -related mechanisms underlying EMT followed by acquired resistance to epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI) in NSCLC. MiRNA expression profiles were examined before and after transforming growth factor-beta1 (TGF-M-NM-21) exposure in four human adenocarcinoma cell lines with or without EMT. Correlation between expressions of EMT-related miRNAs and resistance to EGFR-TKI gefitinib was evaluated. MiRNA array and quantitative RT-PCR revealed that TGF-M-NM-21 significantly induced overexpression of miR-134, miR-487b, and miR-655, which belong to the same cluster located on chromosome 14q32, in lung adenocarcinoma cells with EMT. MAGI2 (membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2), a predicted target of these miRNAs and a scaffold protein required for PTEN (phosphatase and tensin homolog), was diminished in A549 cells with EMT after the TGF-M-NM-21 stimulation. Overexpression of miR-134 and miR-487b promoted the EMT phenomenon and affected the drug resistance to gefitinib, whereas knockdown of these miRNAs inhibited the EMT process and reversed TGF-M-NM-21-induced resistance to gefitinib. Our study demonstrated that the miR-134/487b/655 cluster contributed to the TGF-M-NM-21-induced EMT phenomenon and affected the resistance to gefitinib by directly targeting MAGI2, whose suppression subsequently caused loss of PTEN stability in lung cancer cells. The miR-134/miR-487b/miR-655 cluster may be new therapeutic targets in advanced lung adenocarcinoma patients, depending on the EMT phenomenon. miRNA expression profiles before and after TGF-M-NM-21 exposure were assessed in the four lung adenocarcinoma cell lines, A549, LC2/ad, PC3, and, PC9 by TaqMan miRNA arrays. Relative ratios of miRNAs in cells after TGF-M-NM-21 exposure were calculated when compared with the cells before TGF-M-NM-21 exposure.

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LncRNA SNHG5 suppresses cell migration and invasion of human lung adenocarcinoma via regulation of epithelial-mesenchymal transition

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