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Long noncoding RNA MIR31HG inhibits hepatocellular carcinoma proliferation and metastasis by sponging microRNA-575 to modulate ST7L expression

BACKGROUND: Emerging evidences have indicated that long noncoding RNAs (lncRNAs) play essential roles in the development and progression of cancers. Dysregulation of lncRNA MIR31HG has recently been reported in several types of cancers, and researches on the function of MIR31HG in cancers suggested...

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Autores principales: Yan, Shaoying, Tang, Zhenrong, Chen, Ke, Liu, Yuyang, Yu, Gangfeng, Chen, Qiuxu, Dang, Hao, Chen, Fengjiao, Ling, Jiaji, Zhu, Liying, Huang, Ailong, Tang, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122648/
https://www.ncbi.nlm.nih.gov/pubmed/30176933
http://dx.doi.org/10.1186/s13046-018-0853-9
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author Yan, Shaoying
Tang, Zhenrong
Chen, Ke
Liu, Yuyang
Yu, Gangfeng
Chen, Qiuxu
Dang, Hao
Chen, Fengjiao
Ling, Jiaji
Zhu, Liying
Huang, Ailong
Tang, Hua
author_facet Yan, Shaoying
Tang, Zhenrong
Chen, Ke
Liu, Yuyang
Yu, Gangfeng
Chen, Qiuxu
Dang, Hao
Chen, Fengjiao
Ling, Jiaji
Zhu, Liying
Huang, Ailong
Tang, Hua
author_sort Yan, Shaoying
collection PubMed
description BACKGROUND: Emerging evidences have indicated that long noncoding RNAs (lncRNAs) play essential roles in the development and progression of cancers. Dysregulation of lncRNA MIR31HG has recently been reported in several types of cancers, and researches on the function of MIR31HG in cancers suggested that MIR31HG could act as either oncogene or tumor suppressor. But the functional involvement of MIR31HG has not been studied in hepatocellular carcinoma (HCC). METHODS: In this study, MTS assays, colony formation assay, Wound-healing assay, Transwell assy, and tumor xenografts experiments were used to identify biological effects of MIR31HG on HCC cells HCC proliferation and metastasis in vitro and in vivo. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to show the interactions of MIR31HG and miR-575. The bioinformatics methods were completed to find the target genes of miR-575. And Dual-luciferase reporter assay and Western blot analysis were further used to confirm the target gene of miR-575. RESULTS: We found that overexpression of MIR31HG obviously suppressed HCC proliferation and metastasis in vitro and in vivo, whereas knockdown of MIR31HG had the opposite effects. Besides, overexpression of MIR31HG significantly decreased the expression of microRNA-575 (miR-575), which plays an oncogenic role in HCC. Moreover, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay revealed that MIR31HG exerted tumor-suppressive functions by binding directly to miR-575, and there was a reciprocal inhibition between MIR31HG and miR-575 in the same RNA-induced silencing complex (RISC). Furthermore, overexpression of MIR31HG enhanced the expression of suppression of tumorigenicity 7 like (ST7L), which was identified as a downstream target gene of miR-575. Thus, MIR31HG positively regulated ST7L expression through sponging miR-575, and acted as tumor suppressor in HCC. CONCLUSIONS: Overall, our study illuminates the role of MIR31HG as a miRNA sponge in HCC, and sheds new light on lncRNA-directed diagnostics and therapeutics in HCC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-018-0853-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-61226482018-09-05 Long noncoding RNA MIR31HG inhibits hepatocellular carcinoma proliferation and metastasis by sponging microRNA-575 to modulate ST7L expression Yan, Shaoying Tang, Zhenrong Chen, Ke Liu, Yuyang Yu, Gangfeng Chen, Qiuxu Dang, Hao Chen, Fengjiao Ling, Jiaji Zhu, Liying Huang, Ailong Tang, Hua J Exp Clin Cancer Res Research BACKGROUND: Emerging evidences have indicated that long noncoding RNAs (lncRNAs) play essential roles in the development and progression of cancers. Dysregulation of lncRNA MIR31HG has recently been reported in several types of cancers, and researches on the function of MIR31HG in cancers suggested that MIR31HG could act as either oncogene or tumor suppressor. But the functional involvement of MIR31HG has not been studied in hepatocellular carcinoma (HCC). METHODS: In this study, MTS assays, colony formation assay, Wound-healing assay, Transwell assy, and tumor xenografts experiments were used to identify biological effects of MIR31HG on HCC cells HCC proliferation and metastasis in vitro and in vivo. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to show the interactions of MIR31HG and miR-575. The bioinformatics methods were completed to find the target genes of miR-575. And Dual-luciferase reporter assay and Western blot analysis were further used to confirm the target gene of miR-575. RESULTS: We found that overexpression of MIR31HG obviously suppressed HCC proliferation and metastasis in vitro and in vivo, whereas knockdown of MIR31HG had the opposite effects. Besides, overexpression of MIR31HG significantly decreased the expression of microRNA-575 (miR-575), which plays an oncogenic role in HCC. Moreover, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay revealed that MIR31HG exerted tumor-suppressive functions by binding directly to miR-575, and there was a reciprocal inhibition between MIR31HG and miR-575 in the same RNA-induced silencing complex (RISC). Furthermore, overexpression of MIR31HG enhanced the expression of suppression of tumorigenicity 7 like (ST7L), which was identified as a downstream target gene of miR-575. Thus, MIR31HG positively regulated ST7L expression through sponging miR-575, and acted as tumor suppressor in HCC. CONCLUSIONS: Overall, our study illuminates the role of MIR31HG as a miRNA sponge in HCC, and sheds new light on lncRNA-directed diagnostics and therapeutics in HCC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-018-0853-9) contains supplementary material, which is available to authorized users. BioMed Central 2018-09-03 /pmc/articles/PMC6122648/ /pubmed/30176933 http://dx.doi.org/10.1186/s13046-018-0853-9 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Yan, Shaoying
Tang, Zhenrong
Chen, Ke
Liu, Yuyang
Yu, Gangfeng
Chen, Qiuxu
Dang, Hao
Chen, Fengjiao
Ling, Jiaji
Zhu, Liying
Huang, Ailong
Tang, Hua
Long noncoding RNA MIR31HG inhibits hepatocellular carcinoma proliferation and metastasis by sponging microRNA-575 to modulate ST7L expression
title Long noncoding RNA MIR31HG inhibits hepatocellular carcinoma proliferation and metastasis by sponging microRNA-575 to modulate ST7L expression
title_full Long noncoding RNA MIR31HG inhibits hepatocellular carcinoma proliferation and metastasis by sponging microRNA-575 to modulate ST7L expression
title_fullStr Long noncoding RNA MIR31HG inhibits hepatocellular carcinoma proliferation and metastasis by sponging microRNA-575 to modulate ST7L expression
title_full_unstemmed Long noncoding RNA MIR31HG inhibits hepatocellular carcinoma proliferation and metastasis by sponging microRNA-575 to modulate ST7L expression
title_short Long noncoding RNA MIR31HG inhibits hepatocellular carcinoma proliferation and metastasis by sponging microRNA-575 to modulate ST7L expression
title_sort long noncoding rna mir31hg inhibits hepatocellular carcinoma proliferation and metastasis by sponging microrna-575 to modulate st7l expression
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122648/
https://www.ncbi.nlm.nih.gov/pubmed/30176933
http://dx.doi.org/10.1186/s13046-018-0853-9
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