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.

CircCRIM1 promotes intrahepatic cholangiocarcinoma progression by inhibiting ferroptosis via miR-124-5p/TXNRD1 axis

“…In our previous study, through ICC tissue sequencing, we demonstrated that the expression level of circCRIM1 (hsa_circ_0007386) is signi cantly higher in ICC tissues and ICC cell lines. CircCRIM1 is formed by reverse clipping of the parental gene CRIM1, and CRIM1 clipping has been reported to form a variety of circRNAs, which have been con rmed to be involved in the malignant progression of tumors [4,15,16]. Therefore, we speculate that circCRIM1 may participate in the malignant process of ICC.…”

Circ_0007386 Promotes the Progression of Hepatocellular Carcinoma Through the miR-507/ CCNT2 Axis

“… 9 In another report, circ_0002346 inhibited tumor immune evasion through a competitive combination with IGF2BP1 to mediate non-small cell lung cancer immune evasion. 19 Even in HCC, circCRIM1 (hsa_circ_0002346) has been reported to be a ceRNA that promotes HCC proliferation and angiogenesis. 12 In general, CRIM1-derived circRNAs play an important role in cancers, and some have even become therapeutic targets or prognostic factors; however, their roles in HCC have not been fully elucidated.…”

CircCRIM1/microRNA‐141‐3p/thioredoxin‐binding protein axis mediates neuronal apoptosis after cerebral ischemia‐reperfusion

“…For example, circCRIM1 can function as a ceRNA to promote nasopharyngeal carcinoma metastasis and docetaxel chemoresistance through upregulating FOXQ1 11 . CircCRIM1 knockdown drives IGF2BP1‐mediated immune evasion in non‐small cell lung cancer 12 . CircCRIM1 mediates proliferation, migration, and invasion of trophoblast cells in preeclampsia 13 .…”

“…11 CircCRIM1 knockdown drives IGF2BP1-mediated immune evasion in non-small cell lung cancer. 12 CircCRIM1 mediates proliferation, migration, and invasion of trophoblast cells in preeclampsia. 13 Importantly, a recent high-throughput sequencing analysis of focal cerebral ischemia manifests circCRIM1 is abnormally elevated in the middle cerebral artery occlusion-reperfusion (MCAO/R) model.…”