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

Qi Guo,Xuehan Zhang,Tao Shen,Xiangting Wang

doi:10.3390/life11080835

Abstract

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.

Highlights

Autophagy-dependent cell death was described as a form of regulated cell death (RCD) that mechanistically depends on the autophagic machinery or components [1]
To identify the autophagy and ferroptosis correlated Long non-coding RNAs (lncRNAs) in head and neck squamous cell carcinoma (HNSC), we used autophagic and ferroptotic genes to construct co-expression networks in HNSC patients acrisk groups were assessed by using the Kaplan–Meier survival analysis with the log-rank test
Our results revealed autophagyand ferroptosis-related lncRNAs, analysis

Summary

Introduction

Autophagy-dependent cell death was described as a form of regulated cell death (RCD) that mechanistically depends on the autophagic machinery or components [1]. An increasing number of discoveries have built strong links between autophagy and various types of RCD, including ferroptosis [2,3,4]. Ferroptosis is an iron-dependent form of regulated cell death, which mainly depends on the accumulation of iron and reactive oxygen species (ROS) [5]. Studies have found that autophagic machinery could contribute to ferroptosis by mediating the degradation of ferritin and some genes that are involved in the crosstalk of ferroptosis and autophagy, and contribute to ferroptotic cancer cell death [4,6]. Autophagy and ferroptosis decides cancer cell fate by activating integrated signaling pathways and influencing gene expression programs [3].

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