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. 2022 Jul 6;20:298. doi: 10.1186/s12967-022-03496-3

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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. 4 — In vitro studies revealed that HHLA2 overexpression could reverse the inhibition of cellular functions mediated by METTL3 depletion. We further constructed the HHLA2 overexpression cellular models based on the METTL3 depletion in 786-O and ACHN cells. LV-NC, LV-METTL3-shRNA, LV-NC + LV-HHLA2^OE, and LV-METTL3-shRNA + LV-HHLA2^OE cells were involved in the present study. A and B Based on the qRT-PCR results, the expression of METTL3 at the mRNA level was significantly decreased after METTL3 depletion, and HHLA2 mRNA expression level was significantly increased after HHLA2 overexpression upon METTL3 depletion. C Based on the Western blot analysis, METTL3 protein expression was significantly decreased after METTL3 depletion, and HHLA2 protein expression level was significantly increased after HHLA2 overexpression upon METTL3 depletion. D In 786-O cells, after depletion of METTL3, overexpression of HHLA2 could significantly increase the cellular viability. E In ACHN cells, after depletion of METTL3, overexpression of HHLA2 could significantly increase the cellular viability. Un-paired t test and Two-way ANOVA analyses were used respectively. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001, ^****P < 0.0001