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Epigenetic silencing of LncRNA LINC00261 promotes c-myc-mediated aerobic glycolysis by regulating miR-222-3p/HIPK2/ERK axis and sequestering IGF2BP1
Long noncoding RNAs have been identified as key regulators in the progression of various cancers. LINC00261 has been reported as a tumor suppressor in multiple cancers. However, its function and underlying mechanisms in pancreatic cancer remain largely unclear. Quantitative real-time PCR was perform...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808938/ https://www.ncbi.nlm.nih.gov/pubmed/33122827 http://dx.doi.org/10.1038/s41388-020-01525-3 |
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author | Zhai, Shuyu Xu, Zhiwei Xie, Junjie Zhang, Jun Wang, Xinjing Peng, Chenghong Li, Hongwei Chen, Hao Shen, Baiyong Deng, Xiaxing |
author_facet | Zhai, Shuyu Xu, Zhiwei Xie, Junjie Zhang, Jun Wang, Xinjing Peng, Chenghong Li, Hongwei Chen, Hao Shen, Baiyong Deng, Xiaxing |
author_sort | Zhai, Shuyu |
collection | PubMed |
description | Long noncoding RNAs have been identified as key regulators in the progression of various cancers. LINC00261 has been reported as a tumor suppressor in multiple cancers. However, its function and underlying mechanisms in pancreatic cancer remain largely unclear. Quantitative real-time PCR was performed to detect RNA expression. In situ hybridization was used to discover the subcellular location. The direct binding of LINC00261 to miR-222-3p was verified using a dual-luciferase reporter assay and RNA immunoprecipitation. LINC00261-binding proteins were detected using an RNA pulldown assay. LINC00261 was downregulated in pancreatic cancer tissues and cell lines. Its reduced expression was correlated with advanced pathological stage and poor prognosis. Forced expression of LINC00261 suppressed pancreatic cancer glycolysis and proliferation and induced cell cycle arrest and apoptosis. Mechanistically, downregulation of LINC00261 was caused by hypermethylation of the CpG island in the promoter region and EZH2-mediated histone H3 lysine 27 trimethylation. Moreover, LINC00261 exerted its biological function by binding to miR-222-3p to activate the HIPK2/ERK/c-myc pathway. In addition, LINC00261 could also reduce c-myc expression by sequestering IGF2BP1. Our study suggests that LINC00261 functions as a tumor suppressor in pancreatic cancer and identifies novel epigenetic and posttranscriptional regulatory mechanisms of LINC00261, which contribute to the targeted therapy of pancreatic cancer. |
format | Online Article Text |
id | pubmed-7808938 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-78089382021-01-21 Epigenetic silencing of LncRNA LINC00261 promotes c-myc-mediated aerobic glycolysis by regulating miR-222-3p/HIPK2/ERK axis and sequestering IGF2BP1 Zhai, Shuyu Xu, Zhiwei Xie, Junjie Zhang, Jun Wang, Xinjing Peng, Chenghong Li, Hongwei Chen, Hao Shen, Baiyong Deng, Xiaxing Oncogene Article Long noncoding RNAs have been identified as key regulators in the progression of various cancers. LINC00261 has been reported as a tumor suppressor in multiple cancers. However, its function and underlying mechanisms in pancreatic cancer remain largely unclear. Quantitative real-time PCR was performed to detect RNA expression. In situ hybridization was used to discover the subcellular location. The direct binding of LINC00261 to miR-222-3p was verified using a dual-luciferase reporter assay and RNA immunoprecipitation. LINC00261-binding proteins were detected using an RNA pulldown assay. LINC00261 was downregulated in pancreatic cancer tissues and cell lines. Its reduced expression was correlated with advanced pathological stage and poor prognosis. Forced expression of LINC00261 suppressed pancreatic cancer glycolysis and proliferation and induced cell cycle arrest and apoptosis. Mechanistically, downregulation of LINC00261 was caused by hypermethylation of the CpG island in the promoter region and EZH2-mediated histone H3 lysine 27 trimethylation. Moreover, LINC00261 exerted its biological function by binding to miR-222-3p to activate the HIPK2/ERK/c-myc pathway. In addition, LINC00261 could also reduce c-myc expression by sequestering IGF2BP1. Our study suggests that LINC00261 functions as a tumor suppressor in pancreatic cancer and identifies novel epigenetic and posttranscriptional regulatory mechanisms of LINC00261, which contribute to the targeted therapy of pancreatic cancer. Nature Publishing Group UK 2020-10-29 2021 /pmc/articles/PMC7808938/ /pubmed/33122827 http://dx.doi.org/10.1038/s41388-020-01525-3 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Zhai, Shuyu Xu, Zhiwei Xie, Junjie Zhang, Jun Wang, Xinjing Peng, Chenghong Li, Hongwei Chen, Hao Shen, Baiyong Deng, Xiaxing Epigenetic silencing of LncRNA LINC00261 promotes c-myc-mediated aerobic glycolysis by regulating miR-222-3p/HIPK2/ERK axis and sequestering IGF2BP1 |
title | Epigenetic silencing of LncRNA LINC00261 promotes c-myc-mediated aerobic glycolysis by regulating miR-222-3p/HIPK2/ERK axis and sequestering IGF2BP1 |
title_full | Epigenetic silencing of LncRNA LINC00261 promotes c-myc-mediated aerobic glycolysis by regulating miR-222-3p/HIPK2/ERK axis and sequestering IGF2BP1 |
title_fullStr | Epigenetic silencing of LncRNA LINC00261 promotes c-myc-mediated aerobic glycolysis by regulating miR-222-3p/HIPK2/ERK axis and sequestering IGF2BP1 |
title_full_unstemmed | Epigenetic silencing of LncRNA LINC00261 promotes c-myc-mediated aerobic glycolysis by regulating miR-222-3p/HIPK2/ERK axis and sequestering IGF2BP1 |
title_short | Epigenetic silencing of LncRNA LINC00261 promotes c-myc-mediated aerobic glycolysis by regulating miR-222-3p/HIPK2/ERK axis and sequestering IGF2BP1 |
title_sort | epigenetic silencing of lncrna linc00261 promotes c-myc-mediated aerobic glycolysis by regulating mir-222-3p/hipk2/erk axis and sequestering igf2bp1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808938/ https://www.ncbi.nlm.nih.gov/pubmed/33122827 http://dx.doi.org/10.1038/s41388-020-01525-3 |
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