Family With Sequence Similarity 83, Member A (FAM83A) inhibits ferroptosis via wnt/β-catenin pathway in Lung Squamous Cell Cancer

Author:

Lu Ming1,Wang Cong2,Zhang Jing3,Wang Hongjiao4,Chen Ruixue5

Affiliation:

1. Qilu Hospital

2. Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University,

3. Tai’an Institute For Food And Drug Control (Tai’an Fiber Inspection Institute)

4. Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University

5. Xintai Hospital of Traditional Chinese Medicine

Abstract

Abstract

Background FAM83A function in LUSC is largely unknown. We detected its prognosis and regulation role in LUSC. Methods The bioinformatics methods were performed initially to predict the expression level and prognostic value of FAM83A mRNA in LUSC. In vitro experiments, such as western blot, colony formation and cell viability assay, lipid ROS, MDA and GSH/GSSG and 4-HNE assay were used for the mechanism validation. Results Results from TCGA and Oncomine databases revealed that FAM83A mRNA expression level was significantly higher in LUSC than that in normal lung tissue. TCGA and GEO databases and our database revealed that FAM83A expression level was independent prognostic factor for both OS and PFS. Besides, FAM83A was significantly associated with higher ability of growth and clonogenicity. Mechanically, FAM83A could promote LUSC cell growth by inhibiting ferroptosis via activating Wnt/β-catenin signaling pathway. Rescue experiment demonstrated the inhibition of wnt/β-catenin pathway could counteract the function of FAM83A. Conclusion FAM83A was overexpressed in LUSC and it could serve as a prognosis prediction biomarker for LUSC. FAM83A promotes LUSC cell growth by inhibiting ferroptosis via activating wnt/β-catenin signaling pathway, which provides a new potential therapeutic target for LUSC treatment.

Publisher

Springer Science and Business Media LLC

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