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. 2020 Nov 23;39:256. doi: 10.1186/s13046-020-01772-y

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© The Author(s) 2020

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. 8 — VANGL1 stimulated a DNA repair signal, BRAF/TP53BP1/RAD51. A549 and H1299 cells with or without VANGL1 knockdown were exposed to 2 Gy irradiation. a IP assay was performed to detect the interaction between VANGL1 and BRAF protein. Aa: western blot charts; Ab: the bar charts of protein levels. ***P < 0.001 vs. 2 Gy group. Unpaired two-tailed t-tests (n = 3). b CHX was added to block BRAF protein synthesis. Western blot assay was performed to detect BRAF protein level during 0 ~ 16 h. c Western blot assay was performed to detect levels of VANGL1, BRAF, TP53BP1 and RAD51 in A549 and H1299 cells. **P < 0.01 and ***P < 0.001 vs. control group. One-way analysis of variance (ANOVA) with post-hoc Dunnett’s testing (n = 3). d shows the molecular mechanism underlying VANGL1-mediated adaptive response of LUAD to irradiation. Briefly, irradiation increased the m6A level of VANGL1. IGF2BP2/3 increased VANGL1 mRNA stability in a m6A-dependent manner. Irradiation-induced deficiency of miR-29b-3p in turn increased VANGL1 expression. VANGL1 further increases the expression of BRAF and the downstream effectors, TP53BP1 and RAD51, through which VANGL1 promotes DNA repair after it is damage upon irradiation