Hypoxia Enhances Activity and Malignant Behaviors of Colorectal Cancer Cells through the STAT3/MicroRNA-19a/PTEN/PI3K/AKT Axis

Hypoxia is a typical microenvironment feature in almost all solid tumors and is frequently associated with growth of cancers including colorectal cancer (CRC). This study focuses on the influence of hypoxic microenvironment on the activity of CRC cells and the molecules involved. CRC cells were cult...

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Autores principales: Yingchun Tang, Xiahui Weng, Chang Liu, Xing Li, Chao Chen
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Lenguaje:EN
Publicado: Hindawi Limited 2021
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Acceso en línea:https://doaj.org/article/3379d82621f24185866592cda52aaa0b
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spelling oai:doaj.org-article:3379d82621f24185866592cda52aaa0b2021-11-22T01:11:38ZHypoxia Enhances Activity and Malignant Behaviors of Colorectal Cancer Cells through the STAT3/MicroRNA-19a/PTEN/PI3K/AKT Axis2210-718510.1155/2021/4132488https://doaj.org/article/3379d82621f24185866592cda52aaa0b2021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/4132488https://doaj.org/toc/2210-7185Hypoxia is a typical microenvironment feature in almost all solid tumors and is frequently associated with growth of cancers including colorectal cancer (CRC). This study focuses on the influence of hypoxic microenvironment on the activity of CRC cells and the molecules involved. CRC cells were cultured under hypoxic conditions for 48 h, after which the proliferation, migration, invasion, and epithelial-mesenchymal transition activities of cells were increased. MicroRNA- (miR-) 19a was significantly upregulated in cells after hypoxia exposure according to a microarray analysis. STAT3 was confirmed as an upstream regulator of miR-19a which bound to the promoter region of miR-19a at the 96 bp/78 bp sites, and miR-19a bound to the PTEN mRNA to activate the PI3K/AKT signaling pathway. Hypoxia exposure induced STAT3 phosphorylation and PTEN knockdown in CRC cells. Silencing of STAT3 reduced the hypoxia-induced activity of CRC cells, whereas the malignant behaviors of cells were restored after miR-19a upregulation but blocked after PTEN overexpression. Similar results were reproduced in vivo where downregulation of STAT3 or overexpression of PTEN suppressed tumor growth and metastasis in nude mice. This study demonstrated that hypoxia augments activity and malignant behaviors of colorectal cancer cells through the STAT3/miR-19a/PTEN/PI3K/AKT axis.Yingchun TangXiahui WengChang LiuXing LiChao ChenHindawi LimitedarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENAnalytical Cellular Pathology, Vol 2021 (2021)
institution DOAJ
collection DOAJ
language EN
topic Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Cytology
QH573-671
spellingShingle Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Cytology
QH573-671
Yingchun Tang
Xiahui Weng
Chang Liu
Xing Li
Chao Chen
Hypoxia Enhances Activity and Malignant Behaviors of Colorectal Cancer Cells through the STAT3/MicroRNA-19a/PTEN/PI3K/AKT Axis
description Hypoxia is a typical microenvironment feature in almost all solid tumors and is frequently associated with growth of cancers including colorectal cancer (CRC). This study focuses on the influence of hypoxic microenvironment on the activity of CRC cells and the molecules involved. CRC cells were cultured under hypoxic conditions for 48 h, after which the proliferation, migration, invasion, and epithelial-mesenchymal transition activities of cells were increased. MicroRNA- (miR-) 19a was significantly upregulated in cells after hypoxia exposure according to a microarray analysis. STAT3 was confirmed as an upstream regulator of miR-19a which bound to the promoter region of miR-19a at the 96 bp/78 bp sites, and miR-19a bound to the PTEN mRNA to activate the PI3K/AKT signaling pathway. Hypoxia exposure induced STAT3 phosphorylation and PTEN knockdown in CRC cells. Silencing of STAT3 reduced the hypoxia-induced activity of CRC cells, whereas the malignant behaviors of cells were restored after miR-19a upregulation but blocked after PTEN overexpression. Similar results were reproduced in vivo where downregulation of STAT3 or overexpression of PTEN suppressed tumor growth and metastasis in nude mice. This study demonstrated that hypoxia augments activity and malignant behaviors of colorectal cancer cells through the STAT3/miR-19a/PTEN/PI3K/AKT axis.
format article
author Yingchun Tang
Xiahui Weng
Chang Liu
Xing Li
Chao Chen
author_facet Yingchun Tang
Xiahui Weng
Chang Liu
Xing Li
Chao Chen
author_sort Yingchun Tang
title Hypoxia Enhances Activity and Malignant Behaviors of Colorectal Cancer Cells through the STAT3/MicroRNA-19a/PTEN/PI3K/AKT Axis
title_short Hypoxia Enhances Activity and Malignant Behaviors of Colorectal Cancer Cells through the STAT3/MicroRNA-19a/PTEN/PI3K/AKT Axis
title_full Hypoxia Enhances Activity and Malignant Behaviors of Colorectal Cancer Cells through the STAT3/MicroRNA-19a/PTEN/PI3K/AKT Axis
title_fullStr Hypoxia Enhances Activity and Malignant Behaviors of Colorectal Cancer Cells through the STAT3/MicroRNA-19a/PTEN/PI3K/AKT Axis
title_full_unstemmed Hypoxia Enhances Activity and Malignant Behaviors of Colorectal Cancer Cells through the STAT3/MicroRNA-19a/PTEN/PI3K/AKT Axis
title_sort hypoxia enhances activity and malignant behaviors of colorectal cancer cells through the stat3/microrna-19a/pten/pi3k/akt axis
publisher Hindawi Limited
publishDate 2021
url https://doaj.org/article/3379d82621f24185866592cda52aaa0b
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AT xiahuiweng hypoxiaenhancesactivityandmalignantbehaviorsofcolorectalcancercellsthroughthestat3microrna19aptenpi3kaktaxis
AT changliu hypoxiaenhancesactivityandmalignantbehaviorsofcolorectalcancercellsthroughthestat3microrna19aptenpi3kaktaxis
AT xingli hypoxiaenhancesactivityandmalignantbehaviorsofcolorectalcancercellsthroughthestat3microrna19aptenpi3kaktaxis
AT chaochen hypoxiaenhancesactivityandmalignantbehaviorsofcolorectalcancercellsthroughthestat3microrna19aptenpi3kaktaxis
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