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NF-κB-Induced Upregulation of miR-548as-3p Increases Invasion of NSCLC by Targeting PTEN       
Yazarlar
Şakir Akgün
Kafkas Üniversitesi, Türkiye
Dr. Öğr. Üyesi Hakan KÜÇÜKSAYAN
Kastamonu Üniversitesi, Türkiye
Osman Nidai Özeş
Türkiye
Özge Alvur
Türkiye
Arsenal Sezgin Alikanoğlu
Sağlık Bilimleri Üniversitesi, Türkiye
Mustafa Yıldız
Sağlık Bilimleri Üniversitesi, Türkiye
Hakan Akça
Pamukkale Üniversitesi, Türkiye
Özet
Background: Non-Small Cell Lung Cancer (NSCLC) is an aggressive cancer type due to high metastatic capacity. Nuclear Factor Kappa B (NF-κB) is a consistently active transcription factor in malignant lung cancer cells and has crucial significance in NSCLC progression. It is also implicated in the transcriptional regulation of many genes including microRNAs (miRNAs) that function as tumor suppressor or oncogene. It has been increasingly reported that several miRNAs defined as gene members are induced by NF-κB. The present study aimed to find novel miRNAs that are regulated by NF-κB. Methods: Chromatin Immunoprecipitation Sequencing (ChIP-Seq) experiment and bioinformatic analysis were used to determine NF-κB-dependent miRNAs. Western blot analysis, quantitative real-time polymerase chain reaction (qRT-PCR), luciferase reporter gene assays were carried out to investigate the target genes of miRNAs. To determine biologic activity, transwell invasion and MTT assay were carried out on H1299 NSCLC cell line. miRNA expression level was evaluated in metastatic and non-metastatic tissue samples of NSCLC patients. Results: ChIP-Seq and qRT-PCR experiments showed that miR-548as-3p is transcriptionally regulated by NF-κB in response to Tumor Necrosis Factor-α (TNF-α) treatment. Then, we found that tumor suppressor Phosphatase and Tension homolog (PTEN) is a direct target of miR-548as-3p. Furthermore, miR-548as-3p mediates phosphatidylinositol-3-OH kinase (PI3K)/Akt pathway and NF-κB-implicated genes including Matrix Metalloproteinases 9 (MMP9), Slug and Zeb1. We further showed that miR-548as-3p increased invasiveness of NSCLC cells and was upregulated in metastatic tumor tissues compared to non-metastatic ones. Conclusion: All these findings provide a miRNAs-mediated novel mechanism for NF-κB signaling and that miR-548as-3p could be a biomarker for NSCLC metastasis.
Anahtar Kelimeler
Carcinoma | Invasion | miR-548as-3p | Neoplasm metastasis | NF-kappa B | Non-small-cell lung | PTEN
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
Dergi ISSN 1871-5206
Dergi Tarandığı Indeksler SCI-Expanded
Dergi Grubu Q3
Makale Dili Türkçe
Basım Tarihi 01-2019
Cilt No 19
Sayı 8
Sayfalar 1058 / 1068
Doi Numarası 10.2174/1871520619666190206165215
Makale Linki http://dx.doi.org/10.2174/1871520619666190206165215