Role of Autophagy in the Microenvironment of Oral Squamous Cell Carcinoma

Peña‐Oyarzún, Daniel; Reyes, María Isabel Pávez; Hernández-Cáceres, María Paz; Kretschmar, Catalina; Morselli, Eugenia; Ramírez‐Sarmiento, César A.; Lavandero, Sergio; Torres, Vicente A.; Criollo, Alfredo

doi:10.3389/fonc.2020.602661

Cited by 27 publications

(16 citation statements)

References 105 publications

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“…Autophagy-related genes (ARGs) are molecules that participate in autophagy. In recent studies, many researchers deemed that autophagy is an important process in ORCA [ 6 – 8 ]. Most of the molecular mechanisms which are involved in autophagy regulation deeply participate in signaling pathways that assumed significant roles in ORCA control [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

A Novel Autophagy-Related Prognostic Risk Model and a Nomogram for Survival Prediction of Oral Cancer Patients

Fei

Chen

2022

BioMed Research International

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Background. This study is aimed at constructing a risk signature to predict survival outcomes of ORCA patients. Methods. We identified differentially expressed autophagy-related genes (DEARGs) based on the RNA sequencing data in the TCGA database; then, four independent survival-related ARGs were identified to construct an autophagy-associated signature for survival prediction of ORCA patients. The validity and robustness of the prognostic model were validated by clinicopathological data and survival data. Subsequently, four independent prognostic DEARGs that composed the model were evaluated individually. Results. The expressions of 232 autophagy-related genes (ARGs) in 127 ORCA and 13 control tissues were compared, and 36 DEARGs were filtered out. We performed functional enrichment analysis and constructed protein–protein interaction network for 36 DEARGs. Univariate and multivariate Cox regression analyses were adopted for searching prognostic ARGs, and an autophagy-associated signature for ORCA patients was constructed. Eventually, 4 desirable independent survival-related ARGs (WDR45, MAPK9, VEGFA, and ATIC) were confirmed and comprised the prognostic model. We made use of multiple ways to verify the accuracy of the novel autophagy-related signature for survival evaluation, such as receiver-operator characteristic curve, Kaplan–Meier plotter, and clinicopathological correlational analyses. Four independent prognostic DEARGs that formed the model were also associated with the prognosis of ORCA patients. Conclusions. The autophagy-related risk model can evaluate OS for ORCA patients independently since it is accurate and stable. Four prognostic ARGs that composed the model can be studied deeply for target treatment.

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Section: Introductionmentioning

confidence: 99%

A Novel Autophagy-Related Prognostic Risk Model and a Nomogram for Survival Prediction of Oral Cancer Patients

Fei

Chen

2022

BioMed Research International

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“…Although multiple treatment options are available, such as surgery, radiotherapy, and chemotherapy, the clinical heterogeneity and lack of early detection of HNSC cause the 5-year survival rate to be less than 50% [ 9 ]. Studies have shown that autophagy and ferroptosis are fundamental cellular events, which have been found to affect a variety of characteristics of HNSC, including proliferation, migration, and drug resistance [ 10 , 11 , 12 , 13 ]. While autophagy occurred in tumor cells, the formation of double-membrane autophagic vesicles could be observed by using a transmission electron microscope (TEM) [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Autophagy- and Ferroptosis-Related lncRNAs Functioned through Immune-Related Pathways in Head and Neck Squamous Carcinoma

Guo

Zhang

Shen

et al. 2021

Life

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The interplay between autophagy and ferroptosis has been highlighted as an important event to decide cancer cell fate. However, the underlying mechanisms remain largely unclear. In this study, we systematically explored the expression, prognostic value and functional roles of lncRNA in autophagy and ferroptosis. By a set of bioinformatics analyses, we identified 363 autophagy- and ferroptosis-related lncRNAs (AF-lncRNAs) and found 17 of them are dramatically related to the prognosis of head and neck squamous cell carcinoma (HNSC) patients, named as prognosis-related AF-lncRNAs (PAF-lncRNAs). Based on six key PAF-lncRNAs, a risk score model was developed and used to categorize the TCGA-retrieved HNSC patients into two groups (high-risk vs. low-risk). Functional analysis showed the differentially expressed genes (DEGs) between the two groups were mainly enriched in immune-related pathways and regulated by a PAF-lncRNA-directed ceRNA (competitive endogenous RNA) network. Combined with a variety of immune infiltration analyses, we also found a decreased landscape of immune cell infiltration in high-risk groups. Together, by revealing PAF-lncRNAs with tumor prognostic features functioned through immune-related pathways, our work would contribute to show the pathogenesis of a lncRNA-directed interplay among autophagy, ferroptosis and tumor immunity in HNSC and to develop potential prognostic biomarkers and targets for tumor immunotherapy.

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“…Abnormal autophagy has been associated with cancer and other diseases [ 58 ]. Several studies have demonstrated that autophagy helps cancer cells overcome nutritional limitations and promotes cell growth [ 59 , 60 , 61 ]. Therefore, the inhibition of autophagy in cancer cells appears to be an appropriate treatment strategy.…”

Section: Discussionmentioning

confidence: 99%

Hydroxygenkwanin Increases the Sensitivity of Liver Cancer Cells to Chemotherapy by Inhibiting DNA Damage Response in Mouse Xenograft Models

Chen

Cheng

Shieh

et al. 2021

IJMS

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Molecules involved in DNA damage response (DDR) are often overexpressed in cancer cells, resulting in poor responses to chemotherapy and radiotherapy. Although treatment efficacy can be improved with the concomitant use of DNA repair inhibitors, the accompanying side effects can compromise the quality of life of patients. Therefore, in this study, we identified a natural compound that could inhibit DDR, using the single-strand annealing yeast-cell analysis system, and explored its mechanisms of action and potential as a chemotherapy adjuvant in hepatocellular carcinoma (HCC) cell lines using comet assay, flow cytometry, Western blotting, immunofluorescence staining, and functional analyses. We developed a mouse model to verify the in vitro findings. We found that hydroxygenkwanin (HGK) inhibited the expression of RAD51 and progression of homologous recombination, thereby suppressing the ability of the HCC cell lines to repair DNA damage and enhancing their sensitivity to doxorubicin. HGK inhibited the phosphorylation of DNA damage checkpoint proteins, leading to apoptosis in the HCC cell lines. In the mouse xenograft model, HGK enhanced the sensitivity of liver cancer cells to doxorubicin without any physiological toxicity. Thus, HGK can inhibit DDR in liver cancer cells and mouse models, making it suitable for use as a chemotherapy adjuvant.

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Role of Autophagy in the Microenvironment of Oral Squamous Cell Carcinoma

Cited by 27 publications

References 105 publications

A Novel Autophagy-Related Prognostic Risk Model and a Nomogram for Survival Prediction of Oral Cancer Patients

A Novel Autophagy-Related Prognostic Risk Model and a Nomogram for Survival Prediction of Oral Cancer Patients

Identification of Autophagy- and Ferroptosis-Related lncRNAs Functioned through Immune-Related Pathways in Head and Neck Squamous Carcinoma

Hydroxygenkwanin Increases the Sensitivity of Liver Cancer Cells to Chemotherapy by Inhibiting DNA Damage Response in Mouse Xenograft Models

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