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Background  Our previous report demonstrated that genetic ablation of miR-301a reduces  Kras -driven lung tumorigenesis in mice. However, the impact of miR-301a on host anti-tumor immunity remains unexplored. Here we assessed the underlying molecular mechanisms of miR-301a in the tumor microenvironment.    Methods  The differentially expressed genes were identified by using deep sequencing. The immune cell counts, and cytokines expression were analyzed by realtime PCR, immunohistochemistry and flow cytometry. The role of miR-301a/Runx3 in lung tumor was evaluated on cell growth, migration and invasion. The function of miR-301a/Runx3 in regulating tumor microenvironment and tumor metastasis were evaluated in  Kras  transgenic mice and B16/LLC1 syngeneic xenografts tumor models.    Results  In this work, we identified 1166 up-regulated and 475 down-regulated differentially expressed genes in lung tumor tissues between  Kras   LA2   and  miR-301a   −/−   ; Kras   LA2   mice. Immune response and cell cycle were major pathways involved in the protective role of miR-301a deletion in lung tumorigenesis. Overexpression of the miR-301a target, Runx3, was an early event identified in  miR-301a   −/−   ; Kras   LA2   mice compared to  WT-Kras   LA2   mice. We found that miR-301a deletion enhanced CD8 +  T cell accumulation and IFN-γ production in the tumor microenvironment and mediated antitumor immunity. Further studies revealed that miR-301a deficiency in the tumor microenvironment effectively reduced tumor metastasis by elevating Runx3 and recruiting CD8 +  T cells, whereas miR-301a knockdown in tumor cells themselves restrained cell migration by elevating Runx3 expression.    Conclusions  Our findings further underscore that miR-301a facilitates tumor microenvironment antitumor immunity by Runx3 suppression in lung tumorigenesis.    Electronic supplementary material  The online version of this article (10.1186/s12943-019-1024-0) contains supplementary material, which is available to authorized users.

miR-301a promotes lung tumorigenesis by suppressing Runx3