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. 2022 May 6;21:109. doi: 10.1186/s12943-022-01575-z

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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. 5 — CircMDK functions as a decoy of miR-346 and miR-874-3p to increase ATG16L1 expression. A ceRNA analysis for circMDK by Cytoscape. B Schematic illustration of overlapping target mRNAs of miR-346 and miR-874-3p predicted by MicroCosm, TargetScan, miRDB and miRanda databases. C Relative protein (left) and mRNA (right) levels of ATG16L1 in HCC cells transfected with miR-Ctrl, miR-346 mimic, and miR-874-3p mimic. **p < 0.01. D Relative protein (left) and mRNA (right) levels of ATG16L1 in HCC cells transfected with miR-Ctrl, miR-346 inhibitor, and miR-874-3p inhibitor. **p < 0.01. E Luciferase assay in HCC cells co-transfected WT or mutant (346 Mut/874-3p Mut) ATG16L1 plasmid together with miR-346 and miR-874-3p mimic or miR-Ctrl. **p < 0.01. F Enrichment of ATG16L1 pulled down by biotin-labeled miR-346 and miR-874-3p, or negative control. **p < 0.01. G Relative protein levels of ATG16L1 in four paired HCC samples. pa: para-carcinoma tissues; ca: cancer tissues. H Relative mRNA levels of ATG16L1 in 35 paired HCC samples. mRNA and protein levels of ATG16L1 in four paired HCC samples. ***p < 0.001. I Kaplan–Meier analysis revealed the prognostic values of ATG16L1. J Correlation analysis revealed positive correlation between the levels of circMDK and ATG16L1 mRNA in the tumorous tissues of the 35 HCC patients. K The expression of ATG16L1 in human HCC tissue compared to normal liver tissue. L Relative protein (left) and mRNA (right) levels of ATG16L1 in HCC cells transfected with si-circMDK or si-NC. **p < 0.01. M Relative protein (left) and mRNA (right) levels of ATG16L1 in HCC cells transfected with circMDK overexpression or its empty vector. **p < 0.01. Data are shown as mean ± SD of three independent experiments