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A Yin-Yang 1/miR-30a regulatory circuit modulates autophagy in pancreatic cancer cells

BACKGROUND: Autophagy is a highly regulated biological process that mediates the degradation of intracellular components. It is required for tumor cell metabolism and homeostasis. Yin-Yang 1 (YY1) has been reported to be involved in autophagy in several carcinomas. However, its role in autophagy in...

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Autores principales: Yang, Chuang, Zhang, Jing-Jing, Peng, Yun-Peng, Zhu, Yi, Yin, Ling-Di, Wei, Ji-Shu, Gao, Wen-Tao, Jiang, Kui-Rong, Miao, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5649049/
https://www.ncbi.nlm.nih.gov/pubmed/29052509
http://dx.doi.org/10.1186/s12967-017-1308-3
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author Yang, Chuang
Zhang, Jing-Jing
Peng, Yun-Peng
Zhu, Yi
Yin, Ling-Di
Wei, Ji-Shu
Gao, Wen-Tao
Jiang, Kui-Rong
Miao, Yi
author_facet Yang, Chuang
Zhang, Jing-Jing
Peng, Yun-Peng
Zhu, Yi
Yin, Ling-Di
Wei, Ji-Shu
Gao, Wen-Tao
Jiang, Kui-Rong
Miao, Yi
author_sort Yang, Chuang
collection PubMed
description BACKGROUND: Autophagy is a highly regulated biological process that mediates the degradation of intracellular components. It is required for tumor cell metabolism and homeostasis. Yin-Yang 1 (YY1) has been reported to be involved in autophagy in several carcinomas. However, its role in autophagy in pancreatic cancer, one of the deadliest human malignancies, is unknown. Here, we investigated the function of YY1 in pancreatic cancer cells autophagy and its mechanisms of action. METHODS: The activity of cells undergoing autophagy was assessed using transmission electron microscopy, immunofluorescence, and Western blotting. A luciferase activity assay, real-time quantitative polymerase chain reaction (RT-qPCR), and chromatin immunoprecipitation (ChIP) were also used to identify putative downstream targets of YY1. RESULTS: YY1 was confirmed to regulate autophagy in pancreatic cancer cells. It was found to directly regulate the expression of miR-30a, a known modulator of autophagy-associated genes. Furthermore, overexpression of miR-30a attenuated the pro-autophagic effects of YY1. CONCLUSIONS: Cumulatively, our data suggest that miR-30a acts in a feedback loop to modulate the pro-autophagic activities of YY1. Thus, autophagy in pancreatic cancer cells may be regulated, in part, by a tightly coordinated YY1/miR-30a regulatory circuit. These findings provide a potential druggable target for the development of treatments for pancreatic cancer.
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spelling pubmed-56490492017-10-26 A Yin-Yang 1/miR-30a regulatory circuit modulates autophagy in pancreatic cancer cells Yang, Chuang Zhang, Jing-Jing Peng, Yun-Peng Zhu, Yi Yin, Ling-Di Wei, Ji-Shu Gao, Wen-Tao Jiang, Kui-Rong Miao, Yi J Transl Med Research BACKGROUND: Autophagy is a highly regulated biological process that mediates the degradation of intracellular components. It is required for tumor cell metabolism and homeostasis. Yin-Yang 1 (YY1) has been reported to be involved in autophagy in several carcinomas. However, its role in autophagy in pancreatic cancer, one of the deadliest human malignancies, is unknown. Here, we investigated the function of YY1 in pancreatic cancer cells autophagy and its mechanisms of action. METHODS: The activity of cells undergoing autophagy was assessed using transmission electron microscopy, immunofluorescence, and Western blotting. A luciferase activity assay, real-time quantitative polymerase chain reaction (RT-qPCR), and chromatin immunoprecipitation (ChIP) were also used to identify putative downstream targets of YY1. RESULTS: YY1 was confirmed to regulate autophagy in pancreatic cancer cells. It was found to directly regulate the expression of miR-30a, a known modulator of autophagy-associated genes. Furthermore, overexpression of miR-30a attenuated the pro-autophagic effects of YY1. CONCLUSIONS: Cumulatively, our data suggest that miR-30a acts in a feedback loop to modulate the pro-autophagic activities of YY1. Thus, autophagy in pancreatic cancer cells may be regulated, in part, by a tightly coordinated YY1/miR-30a regulatory circuit. These findings provide a potential druggable target for the development of treatments for pancreatic cancer. BioMed Central 2017-10-19 /pmc/articles/PMC5649049/ /pubmed/29052509 http://dx.doi.org/10.1186/s12967-017-1308-3 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Yang, Chuang
Zhang, Jing-Jing
Peng, Yun-Peng
Zhu, Yi
Yin, Ling-Di
Wei, Ji-Shu
Gao, Wen-Tao
Jiang, Kui-Rong
Miao, Yi
A Yin-Yang 1/miR-30a regulatory circuit modulates autophagy in pancreatic cancer cells
title A Yin-Yang 1/miR-30a regulatory circuit modulates autophagy in pancreatic cancer cells
title_full A Yin-Yang 1/miR-30a regulatory circuit modulates autophagy in pancreatic cancer cells
title_fullStr A Yin-Yang 1/miR-30a regulatory circuit modulates autophagy in pancreatic cancer cells
title_full_unstemmed A Yin-Yang 1/miR-30a regulatory circuit modulates autophagy in pancreatic cancer cells
title_short A Yin-Yang 1/miR-30a regulatory circuit modulates autophagy in pancreatic cancer cells
title_sort yin-yang 1/mir-30a regulatory circuit modulates autophagy in pancreatic cancer cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5649049/
https://www.ncbi.nlm.nih.gov/pubmed/29052509
http://dx.doi.org/10.1186/s12967-017-1308-3
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