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LINC00511 promotes gastric cancer progression by regulating SOX4 and epigenetically repressing PTEN to activate PI3K/AKT pathway

Gastric cancer (GC) serves as a common malignancy. Long non‐coding RNAs (lncRNAs) have been proven to regulate many cancers, including GC. Long intergenic non‐protein‐coding RNA 511 (LINC00511) has been poorly studied in GC, but its detailed regulatory mechanism has not been identified. Here, LINC00...

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Autores principales: Wang, Qianwei, Mao, Xiang, Luo, Fen, Wang, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500959/
https://www.ncbi.nlm.nih.gov/pubmed/34427967
http://dx.doi.org/10.1111/jcmm.16656
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author Wang, Qianwei
Mao, Xiang
Luo, Fen
Wang, Jun
author_facet Wang, Qianwei
Mao, Xiang
Luo, Fen
Wang, Jun
author_sort Wang, Qianwei
collection PubMed
description Gastric cancer (GC) serves as a common malignancy. Long non‐coding RNAs (lncRNAs) have been proven to regulate many cancers, including GC. Long intergenic non‐protein‐coding RNA 511 (LINC00511) has been poorly studied in GC, but its detailed regulatory mechanism has not been identified. Here, LINC00511 was detected to be highly expressed in GC cells. Functional assays were conducted and uncovered that LINC00511 boosted cell proliferation, migration, stemness and EMT process while inhibiting the apoptosis of GC cells. From a series of mechanism experiments, it was found that at the transcriptional level, LINC00511 recruited EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) to the promoter of PTEN (phosphatase and tensin homolog) and facilitated methylation of PTEN promoter. LINC00511 epigenetically repressed PTEN to activate the PI3K/AKT pathway. Moreover, SRY‐box transcription factor 4 (SOX4) activated the transcription of LINC00511. At the post‐transcriptional level, LINC00511 sponged miR‐195‐5p to elevate SOX4 expression in GC cells. On the whole, the present study disclosed that SOX4‐induced LINC00511 activated SOX4 via competing endogenous RNA (ceRNA) pattern and epigenetically repressed PTEN to activate PI3K/AKT pathway by recruiting EZH2, thus facilitating GC cell proliferation, migration and stemness while inhibiting GC cell apoptosis.
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spelling pubmed-85009592021-10-12 LINC00511 promotes gastric cancer progression by regulating SOX4 and epigenetically repressing PTEN to activate PI3K/AKT pathway Wang, Qianwei Mao, Xiang Luo, Fen Wang, Jun J Cell Mol Med Original Articles Gastric cancer (GC) serves as a common malignancy. Long non‐coding RNAs (lncRNAs) have been proven to regulate many cancers, including GC. Long intergenic non‐protein‐coding RNA 511 (LINC00511) has been poorly studied in GC, but its detailed regulatory mechanism has not been identified. Here, LINC00511 was detected to be highly expressed in GC cells. Functional assays were conducted and uncovered that LINC00511 boosted cell proliferation, migration, stemness and EMT process while inhibiting the apoptosis of GC cells. From a series of mechanism experiments, it was found that at the transcriptional level, LINC00511 recruited EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) to the promoter of PTEN (phosphatase and tensin homolog) and facilitated methylation of PTEN promoter. LINC00511 epigenetically repressed PTEN to activate the PI3K/AKT pathway. Moreover, SRY‐box transcription factor 4 (SOX4) activated the transcription of LINC00511. At the post‐transcriptional level, LINC00511 sponged miR‐195‐5p to elevate SOX4 expression in GC cells. On the whole, the present study disclosed that SOX4‐induced LINC00511 activated SOX4 via competing endogenous RNA (ceRNA) pattern and epigenetically repressed PTEN to activate PI3K/AKT pathway by recruiting EZH2, thus facilitating GC cell proliferation, migration and stemness while inhibiting GC cell apoptosis. John Wiley and Sons Inc. 2021-08-24 2021-10 /pmc/articles/PMC8500959/ /pubmed/34427967 http://dx.doi.org/10.1111/jcmm.16656 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Wang, Qianwei
Mao, Xiang
Luo, Fen
Wang, Jun
LINC00511 promotes gastric cancer progression by regulating SOX4 and epigenetically repressing PTEN to activate PI3K/AKT pathway
title LINC00511 promotes gastric cancer progression by regulating SOX4 and epigenetically repressing PTEN to activate PI3K/AKT pathway
title_full LINC00511 promotes gastric cancer progression by regulating SOX4 and epigenetically repressing PTEN to activate PI3K/AKT pathway
title_fullStr LINC00511 promotes gastric cancer progression by regulating SOX4 and epigenetically repressing PTEN to activate PI3K/AKT pathway
title_full_unstemmed LINC00511 promotes gastric cancer progression by regulating SOX4 and epigenetically repressing PTEN to activate PI3K/AKT pathway
title_short LINC00511 promotes gastric cancer progression by regulating SOX4 and epigenetically repressing PTEN to activate PI3K/AKT pathway
title_sort linc00511 promotes gastric cancer progression by regulating sox4 and epigenetically repressing pten to activate pi3k/akt pathway
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500959/
https://www.ncbi.nlm.nih.gov/pubmed/34427967
http://dx.doi.org/10.1111/jcmm.16656
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