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. 2023 Feb 8;21:45. doi: 10.1186/s12951-023-01801-w

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© The Author(s) 2023

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 4 — circCABIN1 promotes cancer stemness. A KEGG pathway analysis demonstrated that positive regulation of stem cell differentiation was involved and might be the downstream of circCABIN1. B GSEA analysis showed that differential genes were mainly enriched in several key stem cell related signal pathways, such as PI3K-Akt and MAPK pathway. C Heat map was performed to analyze the changed key stemness molecules after knockdown of circCABIN1. D The expression of key stemness molecules in LN229 cells were analyzed by western blot after knockdown of circCABIN1. E Fluorescence images showed the expression of circCABIN1 (Red) and ALDH1A3 (Green) in patient samples. Nuclei were counterstained with DAPI (Blue). Scale bar, 50 μm. F Pearson correlation analysis of circCABIN1 and ALDH1A3 (p = 0.0003). G Fluorescence images of patient-derived organoids was to confirm the expression of SOX2 (red) and OCT4 (green) after knockdown of circCABIN1. Nuclei were counterstained with DAPI (blue). Scale bar, 50 μm. H-I Tumorsphere formation assay and colony formation detected GSC’s self-renewal and proliferation ability after knockdown of circCABIN1. J GBM cells administrated with Sen-exo or Res-exo electroporated with circCABIN1^OE/KD were subjected to FACS to detect the proportion of CD44⁺CD133⁺ cells. K Incidences of tumorigenesis of CD45⁺CD133⁺ primary GBM cells (GBM02) infected with circCABIN1^KD in serial transplantation models. **P < 0.01 compared with untreated primary GBM cells in the first inoculation by Fisher’s exact test. L Fluorescence images showed the expression of CD133 (red) and CD44 (green) of brain frozen section from orthotopic GBM xenograft mice in indicated groups. Nuclei were counterstained with DAPI (blue). Scale bar, 10 μm. Results are presented as mean ± SD. *p < 0.05, **p < 0.01 and ***p < 0.001