FOXP3 activated-LINC01232 accelerates the stemness of non-small cell lung carcinoma by activating TGF-β signaling pathway and recruiting IGF2BP2 to stabilize TGFBR1

Non-small cell lung carcinoma (NSCLC) is one of the most common malignant tumors worldwide with high incidence and mortality. Long non-coding RNAs (lncRNAs) have been reported to affect human cancer progression. The present study aimed to investigate the regulatory role and mechanism of long intergenic nonprotein coding RNA 1232 (LINC01232) in NSCLC cells. RT-qPCR results revealed that LINC01232 expression was high in NSCLC cells. Flow cytometry and sphere formation assays indicated that LINC01232 significantly promoted NSCLC cell stemness. Luciferase reporter assay and ChIP assay validated that forkhead box P3 (FOXP3) could bind to LINC01232 promoter and activate LINC01232 transcription. Further, LINC01232 was certified to activate TGF-beta signaling pathway through regulating transforming growth factor beta receptor 1 (TGFBR1). After RIP and RNA pull down assays, insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) was proven as the RNA-binding protein (RBP) for LINC01232. LINC01232 promoted TGFBR1 mRNA stability via recruiting IGF2BP2. Subsequently, LINC01232 was verified to accelerate NSCLC cell stemness and induce macrophage M2 polarization via upregulating TGFBR1. Taken together, FOXP3 activated-LINC01232 accelerated NSCLC cell stemness by activating TGF-beta signaling pathway and recruiting IGF2BP2 to stabilize TGFBR1, which might offer a rationale for lncRNA-based treatment to NSCLC.

Automated summary

This study revealed that LINC01232 played a regulatory role in NSCLC cells by promoting their stemness through activation of the FOXP3-TGF-beta signaling pathway and recruitment of IGF2BP2 to stabilize TGFBR1.