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miR-139-5p functions as a tumor suppressor in cervical cancer by targeting TCF4 and inhibiting Wnt/β-catenin signaling

OBJECTIVES: Dysregulation of microRNAs (miRNAs) has been recognized as a crucial biological event in the development of cervical cancer (CC). miR-139-5p was identified as a significant tumor suppressor in multiple human cancers, leaving its roles and mechanisms in CC absolutely unclear. We aimed to...

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Autores principales: Ji, Xia, Guo, Hairong, Yin, Shanyu, Du, Haiyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759285/
https://www.ncbi.nlm.nih.gov/pubmed/31571923
http://dx.doi.org/10.2147/OTT.S215796
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author Ji, Xia
Guo, Hairong
Yin, Shanyu
Du, Haiyan
author_facet Ji, Xia
Guo, Hairong
Yin, Shanyu
Du, Haiyan
author_sort Ji, Xia
collection PubMed
description OBJECTIVES: Dysregulation of microRNAs (miRNAs) has been recognized as a crucial biological event in the development of cervical cancer (CC). miR-139-5p was identified as a significant tumor suppressor in multiple human cancers, leaving its roles and mechanisms in CC absolutely unclear. We aimed to investigate the implication of miR-139-5p in CC progression. METHODS: miR-139-5p expression in 40 paired CC tissues and several cell lines was determined by qRT-PCR firstly. The implications of miR-139-5p in CC cell proliferation and migration were revealed by CCK-8, EdU and transwell assays, respectively. The mechanism underlying the tumor-suppressing roles of miR-139-5p in CC was investigated sequentially by dual luciferase, qRT-PCR, and Western blot analysis. The expression of transcription factor 4 (TCF4), the validated target of miR-139-5p from our experiments, was finally detected by qRT-PCR and immunohistochemistry in CC tissues, and its expression correlates with miR-139-5p was explored. RESULTS: We found that miR-139-5p expression was frequently decreased in CC tissues and cell lines, and its lower level was associated with positive lymph node metastasis. Cellular assays proved the significant tumor-suppressing roles of miR-139-5p by inhibiting CC cell proliferation and migration, and markedly blocking Wnt/β-catenin signaling. Since bioinformatics analysis indicated TCF4 as a novel target of miR-139-5p, our mechanistic studies validated this, and confirmed that TCF4 restoration could attenuate the tumor inhibitory activities of miR-139-5p in CC progression, and recover the normal Wnt/β-catenin signaling. CONCLUSION: Our data collectively demonstrated that miR-139-5p was a vital tumor suppressor in CC pathogenesis via targeting TCF4 thereby inhibiting Wnt/β-catenin signaling. The miR-139-5p/TCF4 axis may serve as a promising target for CC therapy.
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spelling pubmed-67592852019-09-30 miR-139-5p functions as a tumor suppressor in cervical cancer by targeting TCF4 and inhibiting Wnt/β-catenin signaling Ji, Xia Guo, Hairong Yin, Shanyu Du, Haiyan Onco Targets Ther Original Research OBJECTIVES: Dysregulation of microRNAs (miRNAs) has been recognized as a crucial biological event in the development of cervical cancer (CC). miR-139-5p was identified as a significant tumor suppressor in multiple human cancers, leaving its roles and mechanisms in CC absolutely unclear. We aimed to investigate the implication of miR-139-5p in CC progression. METHODS: miR-139-5p expression in 40 paired CC tissues and several cell lines was determined by qRT-PCR firstly. The implications of miR-139-5p in CC cell proliferation and migration were revealed by CCK-8, EdU and transwell assays, respectively. The mechanism underlying the tumor-suppressing roles of miR-139-5p in CC was investigated sequentially by dual luciferase, qRT-PCR, and Western blot analysis. The expression of transcription factor 4 (TCF4), the validated target of miR-139-5p from our experiments, was finally detected by qRT-PCR and immunohistochemistry in CC tissues, and its expression correlates with miR-139-5p was explored. RESULTS: We found that miR-139-5p expression was frequently decreased in CC tissues and cell lines, and its lower level was associated with positive lymph node metastasis. Cellular assays proved the significant tumor-suppressing roles of miR-139-5p by inhibiting CC cell proliferation and migration, and markedly blocking Wnt/β-catenin signaling. Since bioinformatics analysis indicated TCF4 as a novel target of miR-139-5p, our mechanistic studies validated this, and confirmed that TCF4 restoration could attenuate the tumor inhibitory activities of miR-139-5p in CC progression, and recover the normal Wnt/β-catenin signaling. CONCLUSION: Our data collectively demonstrated that miR-139-5p was a vital tumor suppressor in CC pathogenesis via targeting TCF4 thereby inhibiting Wnt/β-catenin signaling. The miR-139-5p/TCF4 axis may serve as a promising target for CC therapy. Dove 2019-09-20 /pmc/articles/PMC6759285/ /pubmed/31571923 http://dx.doi.org/10.2147/OTT.S215796 Text en © 2019 Ji et al. http://creativecommons.org/licenses/by-nc/3.0/ 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. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Ji, Xia
Guo, Hairong
Yin, Shanyu
Du, Haiyan
miR-139-5p functions as a tumor suppressor in cervical cancer by targeting TCF4 and inhibiting Wnt/β-catenin signaling
title miR-139-5p functions as a tumor suppressor in cervical cancer by targeting TCF4 and inhibiting Wnt/β-catenin signaling
title_full miR-139-5p functions as a tumor suppressor in cervical cancer by targeting TCF4 and inhibiting Wnt/β-catenin signaling
title_fullStr miR-139-5p functions as a tumor suppressor in cervical cancer by targeting TCF4 and inhibiting Wnt/β-catenin signaling
title_full_unstemmed miR-139-5p functions as a tumor suppressor in cervical cancer by targeting TCF4 and inhibiting Wnt/β-catenin signaling
title_short miR-139-5p functions as a tumor suppressor in cervical cancer by targeting TCF4 and inhibiting Wnt/β-catenin signaling
title_sort mir-139-5p functions as a tumor suppressor in cervical cancer by targeting tcf4 and inhibiting wnt/β-catenin signaling
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759285/
https://www.ncbi.nlm.nih.gov/pubmed/31571923
http://dx.doi.org/10.2147/OTT.S215796
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