Cargando…

Role of SIRT1/AMPK signaling in the proliferation, migration and invasion of renal cell carcinoma cells

Renal cell carcinoma (RCC) is a lethal urologic tumor commonly seen in men that best responds to partial nephrectomy. An enhanced understanding of the molecular pathogenesis of RCC can broaden treatment options and tumor prevention strategies. Sirtuin 1 (SIRT1) is a NAD+-dependent deacetylase that r...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Xin, Lu, Youlu, Tuo, Zhouting, Zhou, Huan, Zhang, Ying, Cao, Zhangjun, Peng, Longfei, Yu, Dexin, Bi, Liangkuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082341/
https://www.ncbi.nlm.nih.gov/pubmed/33907836
http://dx.doi.org/10.3892/or.2021.8060
_version_ 1783685828249124864
author Wang, Xin
Lu, Youlu
Tuo, Zhouting
Zhou, Huan
Zhang, Ying
Cao, Zhangjun
Peng, Longfei
Yu, Dexin
Bi, Liangkuan
author_facet Wang, Xin
Lu, Youlu
Tuo, Zhouting
Zhou, Huan
Zhang, Ying
Cao, Zhangjun
Peng, Longfei
Yu, Dexin
Bi, Liangkuan
author_sort Wang, Xin
collection PubMed
description Renal cell carcinoma (RCC) is a lethal urologic tumor commonly seen in men that best responds to partial nephrectomy. An enhanced understanding of the molecular pathogenesis of RCC can broaden treatment options and tumor prevention strategies. Sirtuin 1 (SIRT1) is a NAD+-dependent deacetylase that regulates several bioactive substances, and the present study aimed to identify the role of SIRT1/AMP-activated protein kinase (AMPK) signaling in RCC progression. SIRT1 expression was detected in 100 patients with RCC using tissue microarray immunohistochemistry. SIRT1-knockdown and overexpression were performed via RNA interference and plasmid transfection. Inhibition of AMPK was used for the phenotypic rescue assays to verify whether AMPK was a downstream target of SIRT1. Reverse transcription-quantitative PCR was performed to verify transfection efficiency. Transwell, MTT and flow cytometry apoptosis assays were performed to evaluate the migration, invasion, proliferation and early apoptosis level of RCC cells. SIRT1 and AMPK protein expression in human RCC tissues and cell lines (786-O and ACHN) was detected using western blotting and immunofluorescence staining. The current results, combined with data from The Cancer Genome Atlas database, revealed that SIRT1 expression in RCC tissues was downregulated compared with in adjacent normal tissues. Additionally, high SIRT1 expression was associated with an improved prognosis in patients with RCC. Overexpression of SIRT1 inhibited the proliferation, migration and invasion of RCC cell lines and induced apoptosis, while inhibition of SIRT1 expression had the opposite effects. Further experiments indicated that SIRT1 may serve an anticancer role by upregulating the expression levels of downstream AMPK, thus revealing a potential therapeutic target for RCC.
format Online
Article
Text
id pubmed-8082341
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-80823412021-04-30 Role of SIRT1/AMPK signaling in the proliferation, migration and invasion of renal cell carcinoma cells Wang, Xin Lu, Youlu Tuo, Zhouting Zhou, Huan Zhang, Ying Cao, Zhangjun Peng, Longfei Yu, Dexin Bi, Liangkuan Oncol Rep Articles Renal cell carcinoma (RCC) is a lethal urologic tumor commonly seen in men that best responds to partial nephrectomy. An enhanced understanding of the molecular pathogenesis of RCC can broaden treatment options and tumor prevention strategies. Sirtuin 1 (SIRT1) is a NAD+-dependent deacetylase that regulates several bioactive substances, and the present study aimed to identify the role of SIRT1/AMP-activated protein kinase (AMPK) signaling in RCC progression. SIRT1 expression was detected in 100 patients with RCC using tissue microarray immunohistochemistry. SIRT1-knockdown and overexpression were performed via RNA interference and plasmid transfection. Inhibition of AMPK was used for the phenotypic rescue assays to verify whether AMPK was a downstream target of SIRT1. Reverse transcription-quantitative PCR was performed to verify transfection efficiency. Transwell, MTT and flow cytometry apoptosis assays were performed to evaluate the migration, invasion, proliferation and early apoptosis level of RCC cells. SIRT1 and AMPK protein expression in human RCC tissues and cell lines (786-O and ACHN) was detected using western blotting and immunofluorescence staining. The current results, combined with data from The Cancer Genome Atlas database, revealed that SIRT1 expression in RCC tissues was downregulated compared with in adjacent normal tissues. Additionally, high SIRT1 expression was associated with an improved prognosis in patients with RCC. Overexpression of SIRT1 inhibited the proliferation, migration and invasion of RCC cell lines and induced apoptosis, while inhibition of SIRT1 expression had the opposite effects. Further experiments indicated that SIRT1 may serve an anticancer role by upregulating the expression levels of downstream AMPK, thus revealing a potential therapeutic target for RCC. D.A. Spandidos 2021-06 2021-04-19 /pmc/articles/PMC8082341/ /pubmed/33907836 http://dx.doi.org/10.3892/or.2021.8060 Text en Copyright: © Wang 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
Wang, Xin
Lu, Youlu
Tuo, Zhouting
Zhou, Huan
Zhang, Ying
Cao, Zhangjun
Peng, Longfei
Yu, Dexin
Bi, Liangkuan
Role of SIRT1/AMPK signaling in the proliferation, migration and invasion of renal cell carcinoma cells
title Role of SIRT1/AMPK signaling in the proliferation, migration and invasion of renal cell carcinoma cells
title_full Role of SIRT1/AMPK signaling in the proliferation, migration and invasion of renal cell carcinoma cells
title_fullStr Role of SIRT1/AMPK signaling in the proliferation, migration and invasion of renal cell carcinoma cells
title_full_unstemmed Role of SIRT1/AMPK signaling in the proliferation, migration and invasion of renal cell carcinoma cells
title_short Role of SIRT1/AMPK signaling in the proliferation, migration and invasion of renal cell carcinoma cells
title_sort role of sirt1/ampk signaling in the proliferation, migration and invasion of renal cell carcinoma cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082341/
https://www.ncbi.nlm.nih.gov/pubmed/33907836
http://dx.doi.org/10.3892/or.2021.8060
work_keys_str_mv AT wangxin roleofsirt1ampksignalingintheproliferationmigrationandinvasionofrenalcellcarcinomacells
AT luyoulu roleofsirt1ampksignalingintheproliferationmigrationandinvasionofrenalcellcarcinomacells
AT tuozhouting roleofsirt1ampksignalingintheproliferationmigrationandinvasionofrenalcellcarcinomacells
AT zhouhuan roleofsirt1ampksignalingintheproliferationmigrationandinvasionofrenalcellcarcinomacells
AT zhangying roleofsirt1ampksignalingintheproliferationmigrationandinvasionofrenalcellcarcinomacells
AT caozhangjun roleofsirt1ampksignalingintheproliferationmigrationandinvasionofrenalcellcarcinomacells
AT penglongfei roleofsirt1ampksignalingintheproliferationmigrationandinvasionofrenalcellcarcinomacells
AT yudexin roleofsirt1ampksignalingintheproliferationmigrationandinvasionofrenalcellcarcinomacells
AT biliangkuan roleofsirt1ampksignalingintheproliferationmigrationandinvasionofrenalcellcarcinomacells