Cargando…
The Novel LncRNA WASH5P Inhibits Colorectal Cancer Carcinogenesis via Targeting AKT Signaling Pathway
Emerging evidence has shown that long non-coding RNAs (lncRNAs) play an important role in colorectal cancer (CRC) carcinogenesis, so more specific mechanisms of key lncRNAs in CRC initiation and development are needed. Here, we evaluated the expression profiles of lncRNAs in CRC tissues and identifi...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309812/ https://www.ncbi.nlm.nih.gov/pubmed/35898869 http://dx.doi.org/10.3389/fonc.2022.923425 |
_version_ | 1784753252551622656 |
---|---|
author | Wei, Hongyun Mao, Tao Zhang, Qian Ren, Keyu Qi, Xingsi Zhang, Yunmei Cao, Bin Jin, Yanchun Tian, Zibin Ren, Linlin |
author_facet | Wei, Hongyun Mao, Tao Zhang, Qian Ren, Keyu Qi, Xingsi Zhang, Yunmei Cao, Bin Jin, Yanchun Tian, Zibin Ren, Linlin |
author_sort | Wei, Hongyun |
collection | PubMed |
description | Emerging evidence has shown that long non-coding RNAs (lncRNAs) play an important role in colorectal cancer (CRC) carcinogenesis, so more specific mechanisms of key lncRNAs in CRC initiation and development are needed. Here, we evaluated the expression profiles of lncRNAs in CRC tissues and identified a novel lncRNA generated from the pseudogene Wiskott-Aldrich syndrome protein (WASP) family homolog 5, termed lncRNA WASH5P. However, the role and potential molecular mechanism of this novel lncRNA in diseases, including CRC carcinogenesis, is unknown. Our present study found that WASH5P was significantly downregulated in CRC cell lines and tissues compared with normal controls. The ectopic expression of WASH5P in CRC cells could significantly inhibit CRC cell proliferation, invasion, and migration. In addition, WASH5P could increase the expression of E-cadherin and decrease Vimentin expression. WASH5P-overexpressing CRC cells developed tumors more slowly in different mouse models. Meanwhile, the overexpression of WASH5P could significantly inhibit AKT activation via suppressing AKT phosphorylation. The treatment of PI3K/AKT (phosphatidlinositol 3-kinase /protein kinase B) signaling agonist 740Y-P rescued WASH5P-reduced AKT phosphorylation and abolished the inhibitory effects of WASH5P on cell viability, migration, and invasion. Moreover, 740Y-P restored the WASH5P-induced downregulation of p-AKT and vimentin and the upregulation of E-cadherin via Western blot. In summary, our findings suggested that the novel lncRNA WASH5P might be a potential candidate biomarker and therapeutic target that could inhibit CRC by repressing the AKT signaling pathway. |
format | Online Article Text |
id | pubmed-9309812 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93098122022-07-26 The Novel LncRNA WASH5P Inhibits Colorectal Cancer Carcinogenesis via Targeting AKT Signaling Pathway Wei, Hongyun Mao, Tao Zhang, Qian Ren, Keyu Qi, Xingsi Zhang, Yunmei Cao, Bin Jin, Yanchun Tian, Zibin Ren, Linlin Front Oncol Oncology Emerging evidence has shown that long non-coding RNAs (lncRNAs) play an important role in colorectal cancer (CRC) carcinogenesis, so more specific mechanisms of key lncRNAs in CRC initiation and development are needed. Here, we evaluated the expression profiles of lncRNAs in CRC tissues and identified a novel lncRNA generated from the pseudogene Wiskott-Aldrich syndrome protein (WASP) family homolog 5, termed lncRNA WASH5P. However, the role and potential molecular mechanism of this novel lncRNA in diseases, including CRC carcinogenesis, is unknown. Our present study found that WASH5P was significantly downregulated in CRC cell lines and tissues compared with normal controls. The ectopic expression of WASH5P in CRC cells could significantly inhibit CRC cell proliferation, invasion, and migration. In addition, WASH5P could increase the expression of E-cadherin and decrease Vimentin expression. WASH5P-overexpressing CRC cells developed tumors more slowly in different mouse models. Meanwhile, the overexpression of WASH5P could significantly inhibit AKT activation via suppressing AKT phosphorylation. The treatment of PI3K/AKT (phosphatidlinositol 3-kinase /protein kinase B) signaling agonist 740Y-P rescued WASH5P-reduced AKT phosphorylation and abolished the inhibitory effects of WASH5P on cell viability, migration, and invasion. Moreover, 740Y-P restored the WASH5P-induced downregulation of p-AKT and vimentin and the upregulation of E-cadherin via Western blot. In summary, our findings suggested that the novel lncRNA WASH5P might be a potential candidate biomarker and therapeutic target that could inhibit CRC by repressing the AKT signaling pathway. Frontiers Media S.A. 2022-07-11 /pmc/articles/PMC9309812/ /pubmed/35898869 http://dx.doi.org/10.3389/fonc.2022.923425 Text en Copyright © 2022 Wei, Mao, Zhang, Ren, Qi, Zhang, Cao, Jin, Tian and Ren https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Wei, Hongyun Mao, Tao Zhang, Qian Ren, Keyu Qi, Xingsi Zhang, Yunmei Cao, Bin Jin, Yanchun Tian, Zibin Ren, Linlin The Novel LncRNA WASH5P Inhibits Colorectal Cancer Carcinogenesis via Targeting AKT Signaling Pathway |
title | The Novel LncRNA WASH5P Inhibits Colorectal Cancer Carcinogenesis via Targeting AKT Signaling Pathway |
title_full | The Novel LncRNA WASH5P Inhibits Colorectal Cancer Carcinogenesis via Targeting AKT Signaling Pathway |
title_fullStr | The Novel LncRNA WASH5P Inhibits Colorectal Cancer Carcinogenesis via Targeting AKT Signaling Pathway |
title_full_unstemmed | The Novel LncRNA WASH5P Inhibits Colorectal Cancer Carcinogenesis via Targeting AKT Signaling Pathway |
title_short | The Novel LncRNA WASH5P Inhibits Colorectal Cancer Carcinogenesis via Targeting AKT Signaling Pathway |
title_sort | novel lncrna wash5p inhibits colorectal cancer carcinogenesis via targeting akt signaling pathway |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309812/ https://www.ncbi.nlm.nih.gov/pubmed/35898869 http://dx.doi.org/10.3389/fonc.2022.923425 |
work_keys_str_mv | AT weihongyun thenovellncrnawash5pinhibitscolorectalcancercarcinogenesisviatargetingaktsignalingpathway AT maotao thenovellncrnawash5pinhibitscolorectalcancercarcinogenesisviatargetingaktsignalingpathway AT zhangqian thenovellncrnawash5pinhibitscolorectalcancercarcinogenesisviatargetingaktsignalingpathway AT renkeyu thenovellncrnawash5pinhibitscolorectalcancercarcinogenesisviatargetingaktsignalingpathway AT qixingsi thenovellncrnawash5pinhibitscolorectalcancercarcinogenesisviatargetingaktsignalingpathway AT zhangyunmei thenovellncrnawash5pinhibitscolorectalcancercarcinogenesisviatargetingaktsignalingpathway AT caobin thenovellncrnawash5pinhibitscolorectalcancercarcinogenesisviatargetingaktsignalingpathway AT jinyanchun thenovellncrnawash5pinhibitscolorectalcancercarcinogenesisviatargetingaktsignalingpathway AT tianzibin thenovellncrnawash5pinhibitscolorectalcancercarcinogenesisviatargetingaktsignalingpathway AT renlinlin thenovellncrnawash5pinhibitscolorectalcancercarcinogenesisviatargetingaktsignalingpathway AT weihongyun novellncrnawash5pinhibitscolorectalcancercarcinogenesisviatargetingaktsignalingpathway AT maotao novellncrnawash5pinhibitscolorectalcancercarcinogenesisviatargetingaktsignalingpathway AT zhangqian novellncrnawash5pinhibitscolorectalcancercarcinogenesisviatargetingaktsignalingpathway AT renkeyu novellncrnawash5pinhibitscolorectalcancercarcinogenesisviatargetingaktsignalingpathway AT qixingsi novellncrnawash5pinhibitscolorectalcancercarcinogenesisviatargetingaktsignalingpathway AT zhangyunmei novellncrnawash5pinhibitscolorectalcancercarcinogenesisviatargetingaktsignalingpathway AT caobin novellncrnawash5pinhibitscolorectalcancercarcinogenesisviatargetingaktsignalingpathway AT jinyanchun novellncrnawash5pinhibitscolorectalcancercarcinogenesisviatargetingaktsignalingpathway AT tianzibin novellncrnawash5pinhibitscolorectalcancercarcinogenesisviatargetingaktsignalingpathway AT renlinlin novellncrnawash5pinhibitscolorectalcancercarcinogenesisviatargetingaktsignalingpathway |