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. 2022 Jan 19;21:24. doi: 10.1186/s12943-022-01501-3

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© The Author(s) 2022

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. 3 — circFARP1 enhances the expression and secretion of LIF in CAFs. A Plot showing the sums of the expression levels of genes regulated by circFARP1. B Top 20 enriched pathways of differential mRNA expression between CAFs and circFRAP1-overexpressing CAFs. C Flow chart for the identification of LIF as the downstream target of circFARP1. D-F The mRNA level (D), protein level (E), and secretion level (F) of LIF in CAFs transfected with vector or circFARP1. G-I Panc-1 and MiaPaCa-2 cells were grown in conditioned medium (CM) from CAFs transfected with empty vector or circFARP1 for 2 weeks and subjected to the indicated experiments. Lenti-LIF shRNA or a neutralizing antibody against LIF was used to deplete LIF in CAF-CM. (G) Sphere formation assays of Panc-1 and MiaPaCa-2 cells with the indicated treatments. Scale bars, 50 μm. (H) Flow cytometry analysis of GEM-induced (10 μM) apoptosis in Panc-1 and MiaPaCa-2 cells with the indicated treatment. (I) western blot analysis of pstat3/stat3, ABCC2, CDA, and SOX2 protein expression in Panc-1 and MiaPaCa-2 cells with the indicated treatment. J-L Panc-1 cells were subcutaneously coinjected with or without CAFs stably transfected with lenti-NC-shRNA, lenti-circFARP1-shRNA or lenti-LIF-shRNA into nude mice followed by GEM treatment (50 mg/kg). UT, untreated Panc-1. J Representative images of xenograft tumors of each group. K Tumor growth curve were shown. L Representative images of IHC for α-SMA, SOX2, ABCC2, and CDA in xenograft tumors. Scale bars, 50 μm. Data are expressed as the mean ± SD. ***p<0.001