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  • Title: Circ-HSP90A expedites cell growth, stemness, and immune evasion in non-small cell lung cancer by regulating STAT3 signaling and PD-1/PD-L1 checkpoint.
    Author: Lei J, Zhu J, Hui B, Jia C, Yan X, Jiang T, Wang X.
    Journal: Cancer Immunol Immunother; 2023 Jan; 72(1):101-124. PubMed ID: 35750765.
    Abstract:
    BACKGROUND: Circular RNAs (circRNAs) are important participators in tumor progression for their stable structure and high tissue-specific expression. The purpose of this research was to clarify the potential and mechanism of a novel circRNA-circ-HSP90A in non-small cell lung cancer (NSCLC). METHODS: Biological potentials of circ-HSP90A in NSCLC were measured by functional assays. Molecular interaction was assessed by bioinformatics analysis and mechanical assays. RESULTS: Results depicted that circ-HSP90A was cyclization from its host gene heat shock protein 90 alpha (HSP90A) and was up-regulated in NSCLC cells. Circ-HSP90A depletion retarded proliferation, migration, invasion, and immune evasion. Mechanistically, circ-HSP90A recruited ubiquitin specific peptidase 30 (USP30) to stabilize HSP90A and then stimulated the signal transducer and activator of transcription 3 (STAT3) signaling. Meanwhile, circ-HSP90A sponged miR-424-5p to programmed cell death ligand 1 (PD-L1). CONCLUSIONS: Our study firstly showed that circ-HSP90A promoted cell growth, stemness, and immune evasion in NSCLC through regulating STAT3 signaling and programmed cell death 1 (PD-1)/PD-L1 checkpoint, mirroring that targeting circ-HSP90A might become a novel target of immunotherapy in NSCLC.
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