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PLCL1 suppresses tumour progression by regulating AMPK/mTOR-mediated autophagy in renal cell carcinoma

Autophagy has been increasingly recognized as a critical regulatory mechanism in the maintenance of cellular homeostasis. A previous study showed that phospholipase C-like protein 1 (PLCL1) is associated with lipid metabolism in renal cell carcinoma (RCC). However, it is unclear whether PLCL1 regula...

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Autores principales: Pan, Zhou, Huang, Jing, Song, Huajie, Xiao, Yusha, Liu, Ting, Zeng, Yan, Zhu, Hengcheng, Yang, Kang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10599749/
https://www.ncbi.nlm.nih.gov/pubmed/37801481
http://dx.doi.org/10.18632/aging.205085
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author Pan, Zhou
Huang, Jing
Song, Huajie
Xiao, Yusha
Liu, Ting
Zeng, Yan
Zhu, Hengcheng
Yang, Kang
author_facet Pan, Zhou
Huang, Jing
Song, Huajie
Xiao, Yusha
Liu, Ting
Zeng, Yan
Zhu, Hengcheng
Yang, Kang
author_sort Pan, Zhou
collection PubMed
description Autophagy has been increasingly recognized as a critical regulatory mechanism in the maintenance of cellular homeostasis. A previous study showed that phospholipase C-like protein 1 (PLCL1) is associated with lipid metabolism in renal cell carcinoma (RCC). However, it is unclear whether PLCL1 regulates autophagy, thereby influencing the progression of RCC. Bioinformatics analysis of five microarray datasets revealed that expression of PLCL1 is decreased in tumours and is positively correlated with prognosis in RCC patients. Three independent public datasets, clinical RCC tissues and RCC cell lines, were validated using real-time qPCR, western blotting and immunohistochemistry. Using wound healing and transwell assays, we observed that elevated PLCL1 levels decreased the migratory distance and the invasive number of 786-O and ACHN cells, but PLCL1 knockdown reversed these changes in 769P cell lines compared to those in controls. The results of flow cytometry analysis indicated that PLCL1 promotes apoptosis. Moreover, transcriptional analysis based on stable overexpression of PLCL1 in 786-O cells revealed that PLCL1 is related to autophagy, and western blotting and autophagic experimental results further verified these findings. Mechanistic investigations confirmed that PLCL1 activates the AMPK/mTOR pathway and interacts with decidual protein induced by progesterone (DEPP). Collectively, our data suggest that PLCL1 functions as a suppressor of RCC progression by activating the AMPK/mTOR pathway, interacting with DEPP, initiating autophagy and inducing apoptosis. PLCL1 may be a promising therapeutic target for the diagnosis and treatment of ccRCC patients.
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spelling pubmed-105997492023-10-26 PLCL1 suppresses tumour progression by regulating AMPK/mTOR-mediated autophagy in renal cell carcinoma Pan, Zhou Huang, Jing Song, Huajie Xiao, Yusha Liu, Ting Zeng, Yan Zhu, Hengcheng Yang, Kang Aging (Albany NY) Research Paper Autophagy has been increasingly recognized as a critical regulatory mechanism in the maintenance of cellular homeostasis. A previous study showed that phospholipase C-like protein 1 (PLCL1) is associated with lipid metabolism in renal cell carcinoma (RCC). However, it is unclear whether PLCL1 regulates autophagy, thereby influencing the progression of RCC. Bioinformatics analysis of five microarray datasets revealed that expression of PLCL1 is decreased in tumours and is positively correlated with prognosis in RCC patients. Three independent public datasets, clinical RCC tissues and RCC cell lines, were validated using real-time qPCR, western blotting and immunohistochemistry. Using wound healing and transwell assays, we observed that elevated PLCL1 levels decreased the migratory distance and the invasive number of 786-O and ACHN cells, but PLCL1 knockdown reversed these changes in 769P cell lines compared to those in controls. The results of flow cytometry analysis indicated that PLCL1 promotes apoptosis. Moreover, transcriptional analysis based on stable overexpression of PLCL1 in 786-O cells revealed that PLCL1 is related to autophagy, and western blotting and autophagic experimental results further verified these findings. Mechanistic investigations confirmed that PLCL1 activates the AMPK/mTOR pathway and interacts with decidual protein induced by progesterone (DEPP). Collectively, our data suggest that PLCL1 functions as a suppressor of RCC progression by activating the AMPK/mTOR pathway, interacting with DEPP, initiating autophagy and inducing apoptosis. PLCL1 may be a promising therapeutic target for the diagnosis and treatment of ccRCC patients. Impact Journals 2023-10-06 /pmc/articles/PMC10599749/ /pubmed/37801481 http://dx.doi.org/10.18632/aging.205085 Text en Copyright: © 2023 Pan et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Pan, Zhou
Huang, Jing
Song, Huajie
Xiao, Yusha
Liu, Ting
Zeng, Yan
Zhu, Hengcheng
Yang, Kang
PLCL1 suppresses tumour progression by regulating AMPK/mTOR-mediated autophagy in renal cell carcinoma
title PLCL1 suppresses tumour progression by regulating AMPK/mTOR-mediated autophagy in renal cell carcinoma
title_full PLCL1 suppresses tumour progression by regulating AMPK/mTOR-mediated autophagy in renal cell carcinoma
title_fullStr PLCL1 suppresses tumour progression by regulating AMPK/mTOR-mediated autophagy in renal cell carcinoma
title_full_unstemmed PLCL1 suppresses tumour progression by regulating AMPK/mTOR-mediated autophagy in renal cell carcinoma
title_short PLCL1 suppresses tumour progression by regulating AMPK/mTOR-mediated autophagy in renal cell carcinoma
title_sort plcl1 suppresses tumour progression by regulating ampk/mtor-mediated autophagy in renal cell carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10599749/
https://www.ncbi.nlm.nih.gov/pubmed/37801481
http://dx.doi.org/10.18632/aging.205085
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