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N6-Methyladenosine Modification of LncRNA DUXAP9 Promotes Renal Cancer Cells Proliferation and Motility by Activating the PI3K/AKT Signaling Pathway

Most localized human renal clear cell carcinoma (ccRCC)-related deaths result from cancer recurrence and metastasis. However, the precise molecular mechanisms largely remain unknown. In recent years, an increasing number of long noncoding RNAs (lncRNAs) have been shown to be vital regulators of tumo...

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Autores principales: Tan, Lei, Tang, Yiming, Li, Hongbo, Li, Pengju, Ye, Yunlin, Cen, Junjie, Gui, Chengpeng, Luo, Junhang, Cao, Jiazheng, Wei, Jinhuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217835/
https://www.ncbi.nlm.nih.gov/pubmed/34168980
http://dx.doi.org/10.3389/fonc.2021.641833
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author Tan, Lei
Tang, Yiming
Li, Hongbo
Li, Pengju
Ye, Yunlin
Cen, Junjie
Gui, Chengpeng
Luo, Junhang
Cao, Jiazheng
Wei, Jinhuan
author_facet Tan, Lei
Tang, Yiming
Li, Hongbo
Li, Pengju
Ye, Yunlin
Cen, Junjie
Gui, Chengpeng
Luo, Junhang
Cao, Jiazheng
Wei, Jinhuan
author_sort Tan, Lei
collection PubMed
description Most localized human renal clear cell carcinoma (ccRCC)-related deaths result from cancer recurrence and metastasis. However, the precise molecular mechanisms largely remain unknown. In recent years, an increasing number of long noncoding RNAs (lncRNAs) have been shown to be vital regulators of tumorigenesis. In this study, we characterized a lncRNA DUXAP9 and the upregulation of DUXAP9 was analyzed by quantitative real-time PCR in 112 pairs of localized ccRCC tumor tissues compared with adjacent normal tissues. Kaplan–Meier curves showed that patients of localized ccRCC with high DUXAP9 expression had poorer overall survival (P<0.01) and progression-free survival (P<0.05) than cases with low DUXAP9 expression. Multivariate Cox regression analysis also showed that high DUXAP9 expression was an independent risk factor for poor prognosis in localized ccRCC (p<0.05). DUXAP9 knockdown in renal cancer cells inhibited renal cancer cells proliferation and motility capacities in vitro and reversed epithelial–mesenchymal transition (EMT), whereas overexpression of DUXAP9 promoted renal cancer cells proliferation and motility capacities in vitro and induced EMT. Pull-down, RNA immunoprecipitation and RNA stability assays (involving actinomycin D) showed that DUXAP9 was methylated at N6-adenosine and binds to IGF2BP2, which increases its stability. DUXAP9 activate PI3K/AKT pathway and Snail expression in renal cancer cells. DUXAP9 may be useful as a prognostic marker and/or therapeutic target in localized ccRCC.
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spelling pubmed-82178352021-06-23 N6-Methyladenosine Modification of LncRNA DUXAP9 Promotes Renal Cancer Cells Proliferation and Motility by Activating the PI3K/AKT Signaling Pathway Tan, Lei Tang, Yiming Li, Hongbo Li, Pengju Ye, Yunlin Cen, Junjie Gui, Chengpeng Luo, Junhang Cao, Jiazheng Wei, Jinhuan Front Oncol Oncology Most localized human renal clear cell carcinoma (ccRCC)-related deaths result from cancer recurrence and metastasis. However, the precise molecular mechanisms largely remain unknown. In recent years, an increasing number of long noncoding RNAs (lncRNAs) have been shown to be vital regulators of tumorigenesis. In this study, we characterized a lncRNA DUXAP9 and the upregulation of DUXAP9 was analyzed by quantitative real-time PCR in 112 pairs of localized ccRCC tumor tissues compared with adjacent normal tissues. Kaplan–Meier curves showed that patients of localized ccRCC with high DUXAP9 expression had poorer overall survival (P<0.01) and progression-free survival (P<0.05) than cases with low DUXAP9 expression. Multivariate Cox regression analysis also showed that high DUXAP9 expression was an independent risk factor for poor prognosis in localized ccRCC (p<0.05). DUXAP9 knockdown in renal cancer cells inhibited renal cancer cells proliferation and motility capacities in vitro and reversed epithelial–mesenchymal transition (EMT), whereas overexpression of DUXAP9 promoted renal cancer cells proliferation and motility capacities in vitro and induced EMT. Pull-down, RNA immunoprecipitation and RNA stability assays (involving actinomycin D) showed that DUXAP9 was methylated at N6-adenosine and binds to IGF2BP2, which increases its stability. DUXAP9 activate PI3K/AKT pathway and Snail expression in renal cancer cells. DUXAP9 may be useful as a prognostic marker and/or therapeutic target in localized ccRCC. Frontiers Media S.A. 2021-06-08 /pmc/articles/PMC8217835/ /pubmed/34168980 http://dx.doi.org/10.3389/fonc.2021.641833 Text en Copyright © 2021 Tan, Tang, Li, Li, Ye, Cen, Gui, Luo, Cao and Wei 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
Tan, Lei
Tang, Yiming
Li, Hongbo
Li, Pengju
Ye, Yunlin
Cen, Junjie
Gui, Chengpeng
Luo, Junhang
Cao, Jiazheng
Wei, Jinhuan
N6-Methyladenosine Modification of LncRNA DUXAP9 Promotes Renal Cancer Cells Proliferation and Motility by Activating the PI3K/AKT Signaling Pathway
title N6-Methyladenosine Modification of LncRNA DUXAP9 Promotes Renal Cancer Cells Proliferation and Motility by Activating the PI3K/AKT Signaling Pathway
title_full N6-Methyladenosine Modification of LncRNA DUXAP9 Promotes Renal Cancer Cells Proliferation and Motility by Activating the PI3K/AKT Signaling Pathway
title_fullStr N6-Methyladenosine Modification of LncRNA DUXAP9 Promotes Renal Cancer Cells Proliferation and Motility by Activating the PI3K/AKT Signaling Pathway
title_full_unstemmed N6-Methyladenosine Modification of LncRNA DUXAP9 Promotes Renal Cancer Cells Proliferation and Motility by Activating the PI3K/AKT Signaling Pathway
title_short N6-Methyladenosine Modification of LncRNA DUXAP9 Promotes Renal Cancer Cells Proliferation and Motility by Activating the PI3K/AKT Signaling Pathway
title_sort n6-methyladenosine modification of lncrna duxap9 promotes renal cancer cells proliferation and motility by activating the pi3k/akt signaling pathway
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217835/
https://www.ncbi.nlm.nih.gov/pubmed/34168980
http://dx.doi.org/10.3389/fonc.2021.641833
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