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Long noncoding RNA AK126698 inhibits proliferation and migration of non-small cell lung cancer cells by targeting Frizzled-8 and suppressing Wnt/β-catenin signaling pathway

BACKGROUND: Recent studies indicate that long noncoding RNAs (lncRNAs) play a key role in the control of cellular processes such as proliferation, metastasis, and differentiation. The lncRNA dysregulation has been identified in all types of cancer. We previously found that lncRNA AK126698 suppresses...

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Autores principales: Fu, Xiao, Li, Hui, Liu, Chunxiao, Hu, Bin, Li, Tong, Wang, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928661/
https://www.ncbi.nlm.nih.gov/pubmed/27445486
http://dx.doi.org/10.2147/OTT.S100633
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author Fu, Xiao
Li, Hui
Liu, Chunxiao
Hu, Bin
Li, Tong
Wang, Yang
author_facet Fu, Xiao
Li, Hui
Liu, Chunxiao
Hu, Bin
Li, Tong
Wang, Yang
author_sort Fu, Xiao
collection PubMed
description BACKGROUND: Recent studies indicate that long noncoding RNAs (lncRNAs) play a key role in the control of cellular processes such as proliferation, metastasis, and differentiation. The lncRNA dysregulation has been identified in all types of cancer. We previously found that lncRNA AK126698 suppresses cisplatin resistance in A549 cells through the Wnt/β-catenin signaling pathway. However, the clinical significance of lncRNA AK126698 and the molecular mechanisms through which it regulates cancer cell proliferation and migration are largely unknown. METHODS: We examined the expression of lncRNA AK126698 in 56 non-small cell lung cancer (NSCLC) tissue samples and three NSCLC cell lines using quantitative real-time polymerase chain reaction. Gain and loss of function approaches were used to evaluate the biological function of AK126698 in NSCLC cells. The effects of lncRNA AK126698 on cell proliferation were investigated using cell counting kit-8 and 5-ethynyl-2′-deoxyuridine assays, and apoptosis was measured by flow cytometry. Protein levels of AK126698 targets were evaluated by Western blotting. RESULTS: Our results showed that lncRNA AK126698 was significantly downregulated in NSCLC tissues, compared with paired adjacent nontumor tissue samples. Furthermore, lower AK126698 expression was associated with larger tumor size and advanced tumor stage. Ectopic AK126698 expression inhibited cell proliferation and migration and induced apoptosis. Conversely, decreased AK126698 expression promoted cell proliferation and migration and inhibited cell apoptosis. Importantly, we demonstrated that Frizzled-8, a receptor of Wnt/β-catenin pathway, was a target of AK126698. Furthermore, AK126698 could inhibit the activation of Wnt/β-catenin pathway, which was demonstrated by measuring the expression levels of Axin1, β-catenin, c-myc, cyclin D1, and E-cadherin. CONCLUSION: It was found in the study that lncRNA AK126698 inhibits the proliferation and migration of NSCLC cells by targeting Frizzled-8 to suppress the Wnt/β-catenin signaling pathway. It may provide a new target for therapeutic intervention in NSCLC.
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spelling pubmed-49286612016-07-21 Long noncoding RNA AK126698 inhibits proliferation and migration of non-small cell lung cancer cells by targeting Frizzled-8 and suppressing Wnt/β-catenin signaling pathway Fu, Xiao Li, Hui Liu, Chunxiao Hu, Bin Li, Tong Wang, Yang Onco Targets Ther Original Research BACKGROUND: Recent studies indicate that long noncoding RNAs (lncRNAs) play a key role in the control of cellular processes such as proliferation, metastasis, and differentiation. The lncRNA dysregulation has been identified in all types of cancer. We previously found that lncRNA AK126698 suppresses cisplatin resistance in A549 cells through the Wnt/β-catenin signaling pathway. However, the clinical significance of lncRNA AK126698 and the molecular mechanisms through which it regulates cancer cell proliferation and migration are largely unknown. METHODS: We examined the expression of lncRNA AK126698 in 56 non-small cell lung cancer (NSCLC) tissue samples and three NSCLC cell lines using quantitative real-time polymerase chain reaction. Gain and loss of function approaches were used to evaluate the biological function of AK126698 in NSCLC cells. The effects of lncRNA AK126698 on cell proliferation were investigated using cell counting kit-8 and 5-ethynyl-2′-deoxyuridine assays, and apoptosis was measured by flow cytometry. Protein levels of AK126698 targets were evaluated by Western blotting. RESULTS: Our results showed that lncRNA AK126698 was significantly downregulated in NSCLC tissues, compared with paired adjacent nontumor tissue samples. Furthermore, lower AK126698 expression was associated with larger tumor size and advanced tumor stage. Ectopic AK126698 expression inhibited cell proliferation and migration and induced apoptosis. Conversely, decreased AK126698 expression promoted cell proliferation and migration and inhibited cell apoptosis. Importantly, we demonstrated that Frizzled-8, a receptor of Wnt/β-catenin pathway, was a target of AK126698. Furthermore, AK126698 could inhibit the activation of Wnt/β-catenin pathway, which was demonstrated by measuring the expression levels of Axin1, β-catenin, c-myc, cyclin D1, and E-cadherin. CONCLUSION: It was found in the study that lncRNA AK126698 inhibits the proliferation and migration of NSCLC cells by targeting Frizzled-8 to suppress the Wnt/β-catenin signaling pathway. It may provide a new target for therapeutic intervention in NSCLC. Dove Medical Press 2016-06-24 /pmc/articles/PMC4928661/ /pubmed/27445486 http://dx.doi.org/10.2147/OTT.S100633 Text en © 2016 Fu et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Fu, Xiao
Li, Hui
Liu, Chunxiao
Hu, Bin
Li, Tong
Wang, Yang
Long noncoding RNA AK126698 inhibits proliferation and migration of non-small cell lung cancer cells by targeting Frizzled-8 and suppressing Wnt/β-catenin signaling pathway
title Long noncoding RNA AK126698 inhibits proliferation and migration of non-small cell lung cancer cells by targeting Frizzled-8 and suppressing Wnt/β-catenin signaling pathway
title_full Long noncoding RNA AK126698 inhibits proliferation and migration of non-small cell lung cancer cells by targeting Frizzled-8 and suppressing Wnt/β-catenin signaling pathway
title_fullStr Long noncoding RNA AK126698 inhibits proliferation and migration of non-small cell lung cancer cells by targeting Frizzled-8 and suppressing Wnt/β-catenin signaling pathway
title_full_unstemmed Long noncoding RNA AK126698 inhibits proliferation and migration of non-small cell lung cancer cells by targeting Frizzled-8 and suppressing Wnt/β-catenin signaling pathway
title_short Long noncoding RNA AK126698 inhibits proliferation and migration of non-small cell lung cancer cells by targeting Frizzled-8 and suppressing Wnt/β-catenin signaling pathway
title_sort long noncoding rna ak126698 inhibits proliferation and migration of non-small cell lung cancer cells by targeting frizzled-8 and suppressing wnt/β-catenin signaling pathway
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928661/
https://www.ncbi.nlm.nih.gov/pubmed/27445486
http://dx.doi.org/10.2147/OTT.S100633
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