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Silencing of circCRIM1 Drives IGF2BP1-Mediated NSCLC Immune Evasion.


ABSTRACT:

Objectives

Circular RNAs (circRNAs) have been found to have significant impacts on non-small cell lung cancer (NSCLC) progression through various mechanisms. However, the mechanism of circRNAs modulating tumor immune evasion in NSCLC has yet to be well-revealed.

Materials and methods

Through analyzing the expression profiles of circRNAs in NSCLC tissues, RNA FISH, pull-down assay, mass spectrometry analysis, and RIP, circCRIM1 was identified, and its interaction with IGF2BP1 was confirmed. The effects of circCRIM1 on modulating tumor immune evasion were explored via co-culture in vitro and in tumor xenograft models. Subsequently, we evaluated the regulatory effects of circCRIM1 on IGF2BP1 and screened its target genes through RNA sequencing. Finally, we explored the underlying molecular mechanisms that circCRIM1 could regulate the stability of target mRNA.

Results

circCRIM1 was downregulated in NSCLC, and its expression was positively correlated with favorable prognoses. Furthermore, circCRIM1 was more stable than its linear transcript and was mainly localized in the cytoplasm. Mechanistically, circCRIM1 destabilized HLA-F mRNA via competitive binding to IGF2BP1. Importantly, the overexpression of circCRIM1 suppressed the immune evasion of NSCLC and promoted the expressions of Granzyme B, IFN-γ, and TNF-α of CD8+ T and NK cell in vitro co-culture assays and tumor xenograft models.

Conclusions

This study identifies circCRIM1 as a new tumor suppressor that inhibits tumor immune evasion through a competitive combination with IGF2BP1 to destabilize HLA-F mRNA.

SUBMITTER: Peng W 

PROVIDER: S-EPMC9856323 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Silencing of circCRIM1 Drives IGF2BP1-Mediated NSCLC Immune Evasion.

Peng Wenbei W   Ye Linlin L   Xue Qianqian Q   Wei Xiaoshan X   Wang Zihao Z   Xiang Xuan X   Zhang Siyu S   Zhang Pei P   Wang Haolei H   Zhou Qiong Q  

Cells 20230110 2


<h4>Objectives</h4>Circular RNAs (circRNAs) have been found to have significant impacts on non-small cell lung cancer (NSCLC) progression through various mechanisms. However, the mechanism of circRNAs modulating tumor immune evasion in NSCLC has yet to be well-revealed.<h4>Materials and methods</h4>Through analyzing the expression profiles of circRNAs in NSCLC tissues, RNA FISH, pull-down assay, mass spectrometry analysis, and RIP, circCRIM1 was identified, and its interaction with IGF2BP1 was c  ...[more]

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