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Long Noncoding RNA RP5-833A20.1 Suppresses Tumorigenesis In Hepatocellular Carcinoma Through Akt/ERK Pathway By Targeting miR-18a-5p
BACKGROUND: Previous studies indicated that long noncoding RNAs (lncRNAs) played vital roles in the development and progression of hepatocellular carcinoma (HCC). Recently, downregulation of lncRNA RP5‑833A20.1 has been observed in HCC tissues. However, the underlying mechanism by which RP5‑833A20.1...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902849/ https://www.ncbi.nlm.nih.gov/pubmed/31827329 http://dx.doi.org/10.2147/OTT.S219797 |
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author | Chen, Zili Ma, Yifei Pan, Yaozhen Zuo, Shi Zhu, Haitao Yu, Chao Zhu, Changhao Sun, Chengyi |
author_facet | Chen, Zili Ma, Yifei Pan, Yaozhen Zuo, Shi Zhu, Haitao Yu, Chao Zhu, Changhao Sun, Chengyi |
author_sort | Chen, Zili |
collection | PubMed |
description | BACKGROUND: Previous studies indicated that long noncoding RNAs (lncRNAs) played vital roles in the development and progression of hepatocellular carcinoma (HCC). Recently, downregulation of lncRNA RP5‑833A20.1 has been observed in HCC tissues. However, the underlying mechanism by which RP5‑833A20.1 regulates the proliferation and apoptosis in HCC has not been investigated. Thus, this study aimed to investigate the role of RP5‑833A20.1 in the progression of HCC. METHODS: The levels of RP5‑833A20.1 in 30 pairs of HCC tissues and adjacent normal tissues were detected by RT-qPCR. In addition, the effects of RP5‑833A20.1 on cell proliferation, apoptosis and invasion were evaluated by CCK-8, flow cytometric, transwell assays, respectively. Meanwhile, the dual-luciferase reporter system assay was used to explore the interaction of RP5‑833A20.1 and miR-18a-5p in HCC. RESULTS: The level of RP5‑833A20.1 was significantly downregulated in HCC tissues and HCC cell lines. Downregulation of RP5‑833A20.1 markedly promoted the proliferation and invasion of Bel-7402 cells. In addition, overexpression of RP5‑833A20.1 notably inhibited the proliferation and invasion of Huh7 cells. Moreover, overexpression of RP5‑833A20.1 obviously induced the apoptosis of Huh7 cells via increasing the levels of Bax and active caspase 3, and decreasing the levels of Bcl-2, p-Akt and p-ERK. Meanwhile, in vivo experiments performed also indicated that overexpression of RP5-833A20.1 could inhibit the tumorigenesis of subcutaneous Huh7 xenograft in nude mice. Furthermore, bioinformatics and luciferase reporter assay identified that RP5-833A20.1 functioned as a competing endogenous RNA (ceRNA) for miR-18a-5p in HCC. CONCLUSION: In this study, we found that RP5‑833A20.1 was downregulated in HCC tissues. In addition, RP5-833A20.1 could suppress the tumorigenesis in HCC through inhibiting Akt/ERK pathway by acting as a ceRNA for miR-18a-5p. Therefore, RP5-833A20.1 might be a valuable and potential biomarker and therapeutic target for the treatment of HCC. |
format | Online Article Text |
id | pubmed-6902849 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-69028492019-12-11 Long Noncoding RNA RP5-833A20.1 Suppresses Tumorigenesis In Hepatocellular Carcinoma Through Akt/ERK Pathway By Targeting miR-18a-5p Chen, Zili Ma, Yifei Pan, Yaozhen Zuo, Shi Zhu, Haitao Yu, Chao Zhu, Changhao Sun, Chengyi Onco Targets Ther Original Research BACKGROUND: Previous studies indicated that long noncoding RNAs (lncRNAs) played vital roles in the development and progression of hepatocellular carcinoma (HCC). Recently, downregulation of lncRNA RP5‑833A20.1 has been observed in HCC tissues. However, the underlying mechanism by which RP5‑833A20.1 regulates the proliferation and apoptosis in HCC has not been investigated. Thus, this study aimed to investigate the role of RP5‑833A20.1 in the progression of HCC. METHODS: The levels of RP5‑833A20.1 in 30 pairs of HCC tissues and adjacent normal tissues were detected by RT-qPCR. In addition, the effects of RP5‑833A20.1 on cell proliferation, apoptosis and invasion were evaluated by CCK-8, flow cytometric, transwell assays, respectively. Meanwhile, the dual-luciferase reporter system assay was used to explore the interaction of RP5‑833A20.1 and miR-18a-5p in HCC. RESULTS: The level of RP5‑833A20.1 was significantly downregulated in HCC tissues and HCC cell lines. Downregulation of RP5‑833A20.1 markedly promoted the proliferation and invasion of Bel-7402 cells. In addition, overexpression of RP5‑833A20.1 notably inhibited the proliferation and invasion of Huh7 cells. Moreover, overexpression of RP5‑833A20.1 obviously induced the apoptosis of Huh7 cells via increasing the levels of Bax and active caspase 3, and decreasing the levels of Bcl-2, p-Akt and p-ERK. Meanwhile, in vivo experiments performed also indicated that overexpression of RP5-833A20.1 could inhibit the tumorigenesis of subcutaneous Huh7 xenograft in nude mice. Furthermore, bioinformatics and luciferase reporter assay identified that RP5-833A20.1 functioned as a competing endogenous RNA (ceRNA) for miR-18a-5p in HCC. CONCLUSION: In this study, we found that RP5‑833A20.1 was downregulated in HCC tissues. In addition, RP5-833A20.1 could suppress the tumorigenesis in HCC through inhibiting Akt/ERK pathway by acting as a ceRNA for miR-18a-5p. Therefore, RP5-833A20.1 might be a valuable and potential biomarker and therapeutic target for the treatment of HCC. Dove 2019-12-06 /pmc/articles/PMC6902849/ /pubmed/31827329 http://dx.doi.org/10.2147/OTT.S219797 Text en © 2019 Chen 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 Chen, Zili Ma, Yifei Pan, Yaozhen Zuo, Shi Zhu, Haitao Yu, Chao Zhu, Changhao Sun, Chengyi Long Noncoding RNA RP5-833A20.1 Suppresses Tumorigenesis In Hepatocellular Carcinoma Through Akt/ERK Pathway By Targeting miR-18a-5p |
title | Long Noncoding RNA RP5-833A20.1 Suppresses Tumorigenesis In Hepatocellular Carcinoma Through Akt/ERK Pathway By Targeting miR-18a-5p |
title_full | Long Noncoding RNA RP5-833A20.1 Suppresses Tumorigenesis In Hepatocellular Carcinoma Through Akt/ERK Pathway By Targeting miR-18a-5p |
title_fullStr | Long Noncoding RNA RP5-833A20.1 Suppresses Tumorigenesis In Hepatocellular Carcinoma Through Akt/ERK Pathway By Targeting miR-18a-5p |
title_full_unstemmed | Long Noncoding RNA RP5-833A20.1 Suppresses Tumorigenesis In Hepatocellular Carcinoma Through Akt/ERK Pathway By Targeting miR-18a-5p |
title_short | Long Noncoding RNA RP5-833A20.1 Suppresses Tumorigenesis In Hepatocellular Carcinoma Through Akt/ERK Pathway By Targeting miR-18a-5p |
title_sort | long noncoding rna rp5-833a20.1 suppresses tumorigenesis in hepatocellular carcinoma through akt/erk pathway by targeting mir-18a-5p |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902849/ https://www.ncbi.nlm.nih.gov/pubmed/31827329 http://dx.doi.org/10.2147/OTT.S219797 |
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