Hypoxia-induced autophagy drives colorectal cancer initiation and progression by activating the PRKC/PKC-EZR (ezrin) pathway

Qureshi-Baig, Komal; Kuhn, Diana; Viry, Elodie; Pozdeev, Vitaly I.; Schmitz, Martine; Rodriguez, Fabien; Ullmann, Pit; Koncina, Eric; Nurmik, Martin; Frasquilho, Sónia; Nazarov, Petr V.; Zuegel, Nikolaus; Boulmont, Marc; Karapetyan, Yervand; Antunes, Laurent; Val, Daniel; Mittelbronn, Michel; Janji, Bassam; Haan, Serge; Letellier, Elisabeth

doi:10.1080/15548627.2019.1687213

Cited by 119 publications

(74 citation statements)

References 60 publications

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“…Hypoxia is a typical characteristic observed in the tumor microenvironment and drives the aggressiveness of many tumors, such as hepatocellular carcinoma (Kung-Chun Chiu et al, 2019), colorectal cancer (Qureshi-Baig et al, 2019), and esophageal squamous cell carcinoma (Zhang et al, 2019). Under hypoxic conditions, many transcription factors are activated in tumor cells, inducing various downstream signals regulating cell proliferation, motility, and apoptosis (Semenza, 2012).…”

Section: Introductionmentioning

confidence: 99%

Identification of a Hypoxia-Associated Signature for Lung Adenocarcinoma

Cao

et al. 2020

Front. Genet.

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Background: A hypoxia microenvironment plays a role in the initiation and progression of many cancer types, but its involvement in lung adenocarcinoma is still unclear. This study aimed to explore the potential correlation between hypoxia and lung adenocarcinoma and establish the hypoxia-associated gene signature in lung adenocarcinoma. Methods: Lung adenocarcinoma cases were retrieved from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The genes to be included in the hypoxia-associated signature were selected by performing univariate Cox regression analysis and lasso regression analysis. Then, the gene signature was verified by performing a survival analysis and constructing the multiple receiver operating characteristic (ROC) curve. The CIBERSORT tool was then used to investigate the potential correlation between the gene signature and immune cells. Moreover, a nomogram was constructed and evaluated by calculating the C-index. Results: Four genes (XPNPEP1, ANGPTL4, SLC2A1, and PFKP) were included in the final signature. The results showed that patients in the high-risk group showed worse survival than those in the low-risk group. Moreover, we found two types of immune cells (memory activated CD4 + T cell and M0 macrophages) which showed a significant infiltration in the tissues of the high-risk group patients. Conclusion: The hypoxia-associated gene signature established and validated in this study could be used as a potential prognostic factor in lung adenocarcinoma and may guide the immunotherapy choice.

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Section: Introductionmentioning

confidence: 99%

Identification of a Hypoxia-Associated Signature for Lung Adenocarcinoma

Cao

et al. 2020

Front. Genet.

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“…Hypoxia causes damage to vascular endothelial cells, and endothelial dysfunction disrupts blood flow (Mao et al, 2013;Giannarelli et al, 2014;Zhao et al, 2015). The occurrence and development of vascular endothelial injury is an important Abbreviations: AKT1, AKT serine/threonine kinase 1; CCK-8, cell counting Kit-8; CDK2, cyclin-dependent kinase 2; cDNA, complementary DNA; CI, cerebral infarction; circRNAs, circular RNAs; Ctrl, Control; FBS, fetal bovine serum; FISH, Fluorescence in situ hybridization; miRNA, microRNA; OD, optical density; PDK1, pyruvate dehydrogenase kinase 1; PI, propidium iodide; qRT-PCR, quantitative real-time polymerase chain reaction; SAV1, salvador family WW domain containing protein 1; SD, standard deviation; SDS-PAGE, Sodium dodecyl sulfate-Polyacrylamide gel electrophoresis; siRNA, small interfer RNA; tRNA, tranfer ribonucleic acid; WT, wild type; YAP1, Yes-associated protein 1. cause of many diseases, such as cardiovascular and cerebrovascular diseases, diabetes and tumors (Shan et al, 2017;Qureshi-Baig et al, 2019). Insufficient nutrient supply and hypoxia can cause myocardial infarction and stroke (Lim, 2017;Brait et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

circAFF1 Aggravates Vascular Endothelial Cell Dysfunction Mediated by miR-516b/SAV1/YAP1 Axis

et al. 2020

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Pathological vascular endothelial damage caused by hypoxia is the basis of many vascular-related diseases. However, the role of circular RNA in hypoxic vascular injury is still poorly understood. Here, we found that hypoxia induced AFF1 circular RNA (circAFF1) can activate the SAV1/YAP1 and lead to the dysfunction of vascular endothelial cells. In HUV-EC-C and HBEC-5i cells, circAFF1 was upregulated under CoCl 2 induced hypoxic conditions. The abnormal expression of circAFF1 inhibited the proliferation, tube formation, migration of vascular endothelial cells. The effect of circAFF1 is achieved by the adsorption of miR-516b to release SAV1, which in turn causes the phosphorylation of YAP1. Moreover, we found that the upregulation of circAFF1 in 235 Patients with subarachnoid hemorrhage. Taken together, we clarify the role of circAFF1/miR-516b/SAV1/YAP1 axis in vascular endothelial dysfunction and its potential early diagnostic value of disease caused by hypoxia injury in blood vessels.

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“…Previous studies have demonstrated that autophagy is activated in response to hypoxia and other types of stress, and the activation of autophagy contributes to the tumorigenesis of numerous malignancies, including CRC. For example, hypoxia-induced autophagy promotes the occurrence and progression of CRC via the PRKC/PKC-EZR pathway ( 36 ). Che et al reported that miR-20a suppressed hypoxia-induced autophagy by targeting ATG5/FIP200 in CRC ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Hypoxia‑induced circCCDC66 promotes the tumorigenesis of colorectal cancer via the miR‑3140/autophagy pathway

Jin

Zhong

et al. 2020

Int J Mol Med

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Circular RNAs (circRNAs) have been reported to be involved in the progression of colorectal cancer (CRC). However, the biological role of circCCDC66 in CRC remains unclear. Therefore, the present study aimed to elucidate the mechanisms through which circCCDC66 affects the hypoxia-induced progression of CRC. It was found that hypoxia promoted the progression of CRC and upregulated the expression of circCCDC66. Furthermore, circCCDC66-knockdown reduced viability, migration and invasion, and enhanced the apoptosis of hypoxia-exposed CRC cells. Using the starBase database, it was identified that circCCDC66 may bind to miR-3140. Subsequently, it was confirmed that circCCDC66 serves as a sponge of miR-3140 and the depletion of miR-3140 partly abolished the effects of circCCDC66 on the phenotype of hypoxia-exposed CRC cells. In addition, miR-3140 was validated to inhibit the autophagy pathway. The use of an autophagy inducer partially reversed the miR-3140 overexpression-induced inhibition of the viability and invasion, and the promotion of the apoptosis of hypoxia-exposed CRC cells. In summary, the findings of the present study demonstrated that circCCDC66 facilitates the development of CRC cells under hypoxic conditions via regulation of miR-3140/autophagy. These findings may provide a novel therapeutic option for patients with CRC.

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Hypoxia-induced autophagy drives colorectal cancer initiation and progression by activating the PRKC/PKC-EZR (ezrin) pathway

Cited by 119 publications

References 60 publications

Identification of a Hypoxia-Associated Signature for Lung Adenocarcinoma

Identification of a Hypoxia-Associated Signature for Lung Adenocarcinoma

circAFF1 Aggravates Vascular Endothelial Cell Dysfunction Mediated by miR-516b/SAV1/YAP1 Axis

Hypoxia‑induced circCCDC66 promotes the tumorigenesis of colorectal cancer via the miR‑3140/autophagy pathway

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