Hypoxia Enhances Activity and Malignant Behaviors of Colorectal Cancer Cells through the STAT3/MicroRNA-19a/PTEN/PI3K/AKT Axis
Autor: | Chao Chen, Xing Li, Yingchun Tang, Chang Liu, Xiahui Weng |
---|---|
Rok vydání: | 2021 |
Předmět: |
STAT3 Transcription Factor
Cancer Research Article Subject Mice Nude Pathology and Forensic Medicine Metastasis Mice Phosphatidylinositol 3-Kinases Downregulation and upregulation Cell Line Tumor microRNA medicine Animals Humans PTEN STAT3 Protein kinase B RC254-282 PI3K/AKT/mTOR pathway QH573-671 biology Chemistry Akt/PKB signaling pathway PTEN Phosphohydrolase Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cell Biology General Medicine medicine.disease Cell Hypoxia MicroRNAs biology.protein Cancer research Heterografts Molecular Medicine Cytology Colorectal Neoplasms Proto-Oncogene Proteins c-akt Signal Transduction Research Article |
Zdroj: | Analytical Cellular Pathology (Amsterdam) Analytical Cellular Pathology, Vol 2021 (2021) |
ISSN: | 2210-7185 2210-7177 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: | |
Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |