CircCDR1as upregulates autophagy under hypoxia to promote tumor cell survival via AKT/ERK½/mTOR signaling pathways in oral squamous cell carcinomas
| Autor: | Xiao Liang, Wenhao Ren, Ling Gao, Zhichao Dou, Shaoming Li, Keqian Zhi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Oncogene Chemistry lcsh:Cytology Immunology Autophagy Cell Cellular homeostasis Cell Biology 03 medical and health sciences Cellular and Molecular Neuroscience stomatognathic diseases 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Downregulation and upregulation 030220 oncology & carcinogenesis Cancer research medicine Viability assay lcsh:QH573-671 Protein kinase B PI3K/AKT/mTOR pathway |
| Zdroj: | Cell Death and Disease, Vol 10, Iss 10, Pp 1-16 (2019) |
| ISSN: | 2041-4889 |
| Popis: | Autophagy, as an important non-selective degradation mechanism, could promote tumor initiation and progression by maintaining cellular homeostasis and the cell metabolism as well as cell viability. CircCDR1as has been shown to function as an oncogene in cancer progression, however, it remains largely unknown as to how autophagy is regulated by circCDR1as in oral squamous cell carcinoma (OSCC). In this study, we validated the functional roles of circCDR1as in regulation of autophagy in OSCC cells and further investigated how circCDR1as contributed to cell survival via up-regulating autophagy under a hypoxic microenvironment by using combination of human tissue model, in vitro cell experiments and in vivo mice model. We found that hypoxia promoted the expression level of circCDR1as in OSCC cells and elevated autophagy. In addition, circCDR1as further increased hypoxia-mediated autophagy by targeting multiple key regulators of autophagy. We revealed that circCDR1as enhanced autophagy in OSCC cells via inhibition of rapamycin (mTOR) activity and upregulation of AKT and ERK½ pathways. Overexpression of circCDR1as enhanced OSCC cells viability, endoplasmic reticulum (ER) stress, and inhibited cell apoptosis under a hypoxic microenvironment. Moreover, circCDR1as promoted autophagy in OSCC cells by sponging miR-671-5p. Collectively, these results revealed that high expression of circCDR1as enhanced the viability of OSCC cells under a hypoxic microenvironment by promoting autophagy, suggesting a novel treatment strategy involving circCDR1as and the inhibition of autophagy in OSCC cells. |
| Databáze: | OpenAIRE |
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