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http://purl.uniprot.org/citations/35551652http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/35551652http://www.w3.org/2000/01/rdf-schema#comment"

Background

Chemoresistance often causes the failure of treatment and death of patients with advanced non-small-cell lung cancer. However, there is still no resistance genes signature and available enriched signaling derived from a comprehensive RNA-Seq data analysis of lung cancer patients that could act as a therapeutic target to re-sensitize the acquired resistant cancer cells to chemo-drugs. Hence, in this study, we aimed to identify the resistance signature for clinical lung cancer patients and explore the regulatory mechanism.

Method

Analysis of RNA-Seq data from clinical lung cancer patients was conducted in R studio to identify the resistance signature. The resistance signature was validated by survival time of lung cancer patients and qPCR in chemo-resistant cells. Cytokine application, small-interfering RNA and pharmacological inhibition approaches were applied to characterize the function and molecular mechanism of EREG and downstream signaling in chemoresistance regulation via stemness.

Results

The RTK and vitamin D signaling were enriched among resistance genes, where 6 genes were validated as resistance signature and associated with poor survival in patients. EREG/ERK signaling was activated by chemo-drugs in NSCLC cells. EREG protein promoted the NSCLC resistance to chemo-drugs by increasing stemness genes expression. Additionally, inhibition of EREG/ErbB had downregulated ERK signaling, resulting in decreased expression of stemness-associated genes and subsequently re-sensitized the resistant NSCLC cells and spheres to chemo-drugs.

Conclusions

These findings revealed 6 resistance genes signature and proved that EREG/ErbB regulated the stemness to maintain chemoresistance of NSCLC via ERK signaling. Therefore, targeting EREG/ErbB might significantly and effectively resolve the chemoresistance issue."xsd:string
http://purl.uniprot.org/citations/35551652http://purl.org/dc/terms/identifier"doi:10.1186/s13287-022-02859-3"xsd:string
http://purl.uniprot.org/citations/35551652http://purl.uniprot.org/core/author"Hu X."xsd:string
http://purl.uniprot.org/citations/35551652http://purl.uniprot.org/core/author"Li H."xsd:string
http://purl.uniprot.org/citations/35551652http://purl.uniprot.org/core/author"Lu Y."xsd:string
http://purl.uniprot.org/citations/35551652http://purl.uniprot.org/core/author"Lee S.H."xsd:string
http://purl.uniprot.org/citations/35551652http://purl.uniprot.org/core/author"Xu W."xsd:string
http://purl.uniprot.org/citations/35551652http://purl.uniprot.org/core/author"Zhang Y."xsd:string
http://purl.uniprot.org/citations/35551652http://purl.uniprot.org/core/author"Zeng R."xsd:string
http://purl.uniprot.org/citations/35551652http://purl.uniprot.org/core/author"Wang X."xsd:string
http://purl.uniprot.org/citations/35551652http://purl.uniprot.org/core/author"Xu J."xsd:string
http://purl.uniprot.org/citations/35551652http://purl.uniprot.org/core/author"Wang X.'"xsd:string
http://purl.uniprot.org/citations/35551652http://purl.uniprot.org/core/author"Yan X."xsd:string
http://purl.uniprot.org/citations/35551652http://purl.uniprot.org/core/author"Jiang R."xsd:string
http://purl.uniprot.org/citations/35551652http://purl.uniprot.org/core/author"Ye T."xsd:string
http://purl.uniprot.org/citations/35551652http://purl.uniprot.org/core/author"Jia L."xsd:string
http://purl.uniprot.org/citations/35551652http://purl.uniprot.org/core/author"Qiu F."xsd:string
http://purl.uniprot.org/citations/35551652http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/35551652http://purl.uniprot.org/core/name"Stem Cell Res Ther"xsd:string
http://purl.uniprot.org/citations/35551652http://purl.uniprot.org/core/pages"197"xsd:string
http://purl.uniprot.org/citations/35551652http://purl.uniprot.org/core/title"Epiregulin increases stemness-associated genes expression and promotes chemoresistance of non-small cell lung cancer via ERK signaling."xsd:string
http://purl.uniprot.org/citations/35551652http://purl.uniprot.org/core/volume"13"xsd:string
http://purl.uniprot.org/citations/35551652http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/35551652
http://purl.uniprot.org/citations/35551652http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/35551652
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