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NF-κB-Induced Upregulation of miR-548as-3p Increases Invasion of NSCLC by Targeting PTEN

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Bibliographic Details
Title: NF-κB-Induced Upregulation of miR-548as-3p Increases Invasion of NSCLC by Targeting PTEN
Authors: Akgun, S., Kucuksayan, H., Ozes, O.N., Can, O., Alikanoglu, A.S., Yildiz, M., Akca, H.
Source: Anti-Cancer Agents in Medicinal Chemistry. 19:1058-1068
Publisher Information: Bentham Science Publishers Ltd., 2019.
Publication Year: 2019
Subject Terms: 0301 basic medicine, PTEN, Carcinoma, Non-Small-Cell Lung/*genetics/metabolism/*pathology, Cell Survival, Dose-Response Relationship, Drug, HEK293 Cells, Humans, Lung Neoplasms/*genetics/metabolism/*pathology, MicroRNAs/biosynthesis/*genetics, Molecular Structure, NF-kappa B/*metabolism, PTEN Phosphohydrolase/*genetics/metabolism, RNA, Messenger/genetics/metabolism, Structure-Activity Relationship, Up-Regulation, Lung Neoplasms, Western blotting, lung tumor, Invasion, dose response, Carcinoma, Non-Small-Cell Lung, PTEN protein, human, PTEN protein, genetics, phosphatidylinositol 3 kinase, 0303 health sciences, MTT assay, microRNA, transcription factor Slug, messenger RNA, NF-kappa B, bioinformatics, cell invasion, unclassified drug, 3. Good health, miR-548as-3p, immunoglobulin enhancer binding protein, real time polymerase chain reaction, HEK293 cell line, transcription regulation, cancer tissue, signal transduction, microRNA 548as 3p, Neoplasm metastasis, tumor necrosis factor, chromatin immunoprecipitation, gel mobility shift assay, cell survival, Article, gelatinase B, 03 medical and health sciences, promoter region, transcription initiation site, protein targeting, controlled study, human, RNA, Messenger, DNA binding, structure activity relation, non small cell lung cancer, binding site, human cell, Carcinoma, Non-small-cell lung, PTEN Phosphohydrolase, phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase, human tissue, MicroRNAs, gene expression, chemical structure, protein kinase B, MIRN548 microRNA, pathology, MIRN548 microRNA, human, biosynthesis, transcription factor ZEB1, NCI-H1299 cell line, metabolism, upregulation
Description: 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 İmmunoprecipitation 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.
Document Type: Article
Other literature type
Language: English
ISSN: 1871-5206
DOI: 10.2174/1871520619666190206165215
Access URL: https://pubmed.ncbi.nlm.nih.gov/30727918
https://pubmed.ncbi.nlm.nih.gov/30727918/
http://www.eurekaselect.com/169698
http://www.eurekaselect.com/169698/article
https://europepmc.org/article/MED/30727918
https://www.ncbi.nlm.nih.gov/pubmed/30727918
https://avesis.yyu.edu.tr/publication/details/7013df4c-b112-49f1-b4c6-04743cf9ff67/oai
https://aperta.ulakbim.gov.tr/record/74465
Rights: CC BY
Accession Number: edsair.doi.dedup.....5ee1f8d04a6a79a5db3136a8e80be8d8
Database: OpenAIRE
Description
Abstract: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 İmmunoprecipitation 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.
ISSN:18715206
DOI:10.2174/1871520619666190206165215