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Long noncoding RNA LINC00649 functions as a microRNA-432-5p sponge to facilitate tumourigenesis in colorectal cancer by upregulating HDGF
Long intergenic nonprotein coding RNA 649 (LINC00649) is a functional regulator in acute myeloid leukaemia. However, the contribution of LINC00649 in colorectal cancer (CRC) has yet to be confirmed. Accordingly, the present investigation was devoted to exploring the detailed functions of LINC00649 a...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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D.A. Spandidos
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8822880/ https://www.ncbi.nlm.nih.gov/pubmed/35088877 http://dx.doi.org/10.3892/mmr.2022.12620 |
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author | Bao, Junjie Bi, Xiaokai Wang, Jingbo Li, Xiaoqiang |
author_facet | Bao, Junjie Bi, Xiaokai Wang, Jingbo Li, Xiaoqiang |
author_sort | Bao, Junjie |
collection | PubMed |
description | Long intergenic nonprotein coding RNA 649 (LINC00649) is a functional regulator in acute myeloid leukaemia. However, the contribution of LINC00649 in colorectal cancer (CRC) has yet to be confirmed. Accordingly, the present investigation was devoted to exploring the detailed functions of LINC00649 and reveal the mechanisms underlying the LINC00649-induced promotion of CRC progression. LINC00649 expression in CRC was investigated by reverse transcription-quantitative PCR. Knockdown of LINC00649 was achieved using small interfering RNAs or short hairpin RNA, followed by functional experiments. The binding between LINC00649 and microRNA (miR)-432-5p was predicted by a bioinformatics tool, and corroborated by luciferase reporter assay and RNA immunoprecipitation. In the present study, LINC00649 was expressed at a high level in CRC. The aberrant expression of LINC00649 exhibited an inverse association with CRC patient prognosis. Functionally, the downregulation of LINC00649 exerted anticarcinogenic activities in CRC by decreasing cell proliferation, migration, and invasion and inducing cell apoptosis. Furthermore, the growth of CRC cells in vivo was attenuated after LINC00649 deficiency. Mechanistically, LINC00649 functioned as a competitive endogenous RNA by competitively binding to miR-432-5p in CRC cells, inducing an increase in hepatoma-derived growth factor (HDGF). Ultimately, functional rescue experiments highlighted that the exogenous introduction of miR-432-5p inhibitor or HDGF overexpression plasmid partially abated the inhibitory effects of LINC00649 silencing. In conclusion, LINC00649 promoted the aggressiveness of CRC cells by adjusting the miR-432-5p/HDGF axis. Thus, the LINC00649/miR-432-5p/HDGF pathway may be a promising target for CRC therapy. |
format | Online Article Text |
id | pubmed-8822880 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-88228802022-02-10 Long noncoding RNA LINC00649 functions as a microRNA-432-5p sponge to facilitate tumourigenesis in colorectal cancer by upregulating HDGF Bao, Junjie Bi, Xiaokai Wang, Jingbo Li, Xiaoqiang Mol Med Rep Articles Long intergenic nonprotein coding RNA 649 (LINC00649) is a functional regulator in acute myeloid leukaemia. However, the contribution of LINC00649 in colorectal cancer (CRC) has yet to be confirmed. Accordingly, the present investigation was devoted to exploring the detailed functions of LINC00649 and reveal the mechanisms underlying the LINC00649-induced promotion of CRC progression. LINC00649 expression in CRC was investigated by reverse transcription-quantitative PCR. Knockdown of LINC00649 was achieved using small interfering RNAs or short hairpin RNA, followed by functional experiments. The binding between LINC00649 and microRNA (miR)-432-5p was predicted by a bioinformatics tool, and corroborated by luciferase reporter assay and RNA immunoprecipitation. In the present study, LINC00649 was expressed at a high level in CRC. The aberrant expression of LINC00649 exhibited an inverse association with CRC patient prognosis. Functionally, the downregulation of LINC00649 exerted anticarcinogenic activities in CRC by decreasing cell proliferation, migration, and invasion and inducing cell apoptosis. Furthermore, the growth of CRC cells in vivo was attenuated after LINC00649 deficiency. Mechanistically, LINC00649 functioned as a competitive endogenous RNA by competitively binding to miR-432-5p in CRC cells, inducing an increase in hepatoma-derived growth factor (HDGF). Ultimately, functional rescue experiments highlighted that the exogenous introduction of miR-432-5p inhibitor or HDGF overexpression plasmid partially abated the inhibitory effects of LINC00649 silencing. In conclusion, LINC00649 promoted the aggressiveness of CRC cells by adjusting the miR-432-5p/HDGF axis. Thus, the LINC00649/miR-432-5p/HDGF pathway may be a promising target for CRC therapy. D.A. Spandidos 2022-03 2022-01-26 /pmc/articles/PMC8822880/ /pubmed/35088877 http://dx.doi.org/10.3892/mmr.2022.12620 Text en Copyright: © Bao et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Bao, Junjie Bi, Xiaokai Wang, Jingbo Li, Xiaoqiang Long noncoding RNA LINC00649 functions as a microRNA-432-5p sponge to facilitate tumourigenesis in colorectal cancer by upregulating HDGF |
title | Long noncoding RNA LINC00649 functions as a microRNA-432-5p sponge to facilitate tumourigenesis in colorectal cancer by upregulating HDGF |
title_full | Long noncoding RNA LINC00649 functions as a microRNA-432-5p sponge to facilitate tumourigenesis in colorectal cancer by upregulating HDGF |
title_fullStr | Long noncoding RNA LINC00649 functions as a microRNA-432-5p sponge to facilitate tumourigenesis in colorectal cancer by upregulating HDGF |
title_full_unstemmed | Long noncoding RNA LINC00649 functions as a microRNA-432-5p sponge to facilitate tumourigenesis in colorectal cancer by upregulating HDGF |
title_short | Long noncoding RNA LINC00649 functions as a microRNA-432-5p sponge to facilitate tumourigenesis in colorectal cancer by upregulating HDGF |
title_sort | long noncoding rna linc00649 functions as a microrna-432-5p sponge to facilitate tumourigenesis in colorectal cancer by upregulating hdgf |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8822880/ https://www.ncbi.nlm.nih.gov/pubmed/35088877 http://dx.doi.org/10.3892/mmr.2022.12620 |
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