guest ::
| Home > Publications database > Myeloid Mir34a suppresses initiation and progression of intestinal and colitis-induced colon cancers in APCmin mice. |
| Home > Publications database > Myeloid Mir34a suppresses initiation and progression of intestinal and colitis-induced colon cancers in APCmin mice. |
| Journal Article | DKFZ-2026-01150 |
; ; ; ;
2026
Nature Publishing Group
London [u.a.]
Abstract: Here we determined whether myeloid Mir34a has a tumor suppressive function in ApcMin/+ mice, a model for intestinal and colon cancer. Myeloid cell-specific deletion of Mir34a in ApcMin/+ mice increased tumor initiation and allowed progression towards invasive carcinomas, which are generally not observed in ApcMin/+ mice. Loss of Mir34a facilitated the polarization of tumor-associated macrophages (TAMs) towards a pro-tumorigenic M2-like state, implying that Mir34a is required to maintain TAMs in a tumor-suppressive state. Also, Mir34a-deficient, bone-marrow-derived macrophages (BMDMs) from ApcMin/+ mice were polarized towards a pro-tumorigenic, M2-like state and displayed enhanced migration when compared to Mir34a-proficient BMDMs. Intestinal tumors in myeloid Mir34a-deficient mice showed elevated expression of several known Mir34a target mRNAs, including Csf1r, Pd-l1, Mmp9, Ccl22, and c-Myc. In addition, the number of immuno-suppressive, pro-tumorigenic CD4+Foxp3+ Treg cells increased in myeloid Mir34a-deficient intestinal tumors. Moreover, ApcMin/+ mice with myeloid-specific deletion of Mir34a had a significantly diminished survival rate. Following the induction of inflammatory colitis, these mice showed enhanced colon cancer initiation and progression towards invasive carcinomas with an increase in M2-like TAMs, N2-like neutrophils and Treg cells. These findings imply that myeloid Mir34a suppresses tumor formation and progression by maintaining myeloid and T-cells in an anti-tumorigenic state. Therefore, the p53-miR-34a axis has a central role in non-tumor cell mediated suppression of intestinal and colon cancers.
Keyword(s): Animals (MeSH) ; MicroRNAs: genetics (MeSH) ; MicroRNAs: metabolism (MeSH) ; Colonic Neoplasms: pathology (MeSH) ; Colonic Neoplasms: genetics (MeSH) ; Colonic Neoplasms: metabolism (MeSH) ; Mice (MeSH) ; Disease Progression (MeSH) ; Colitis: pathology (MeSH) ; Colitis: complications (MeSH) ; Colitis: genetics (MeSH) ; Myeloid Cells: metabolism (MeSH) ; Myeloid Cells: pathology (MeSH) ; Macrophages: metabolism (MeSH) ; Macrophages: pathology (MeSH) ; Adenomatous Polyposis Coli Protein: metabolism (MeSH) ; Adenomatous Polyposis Coli Protein: genetics (MeSH) ; Carcinogenesis: genetics (MeSH) ; Carcinogenesis: pathology (MeSH) ; Mice, Inbred C57BL (MeSH) ; MicroRNAs ; MIRN34a microRNA, mouse ; Adenomatous Polyposis Coli Protein
; 
; 
; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
|
The record appears in these collections: |
