MiR-124-3p inhibits stomach adenocarcinoma progression by targeting AHR to induce autophagy.

ABSTRACT:

Background

MicroRNA-124-3p (miR-124-3p) has been widely reported as an important tumor-suppressive regulator in multiple malignancies. Nevertheless, its precise biological function in stomach adenocarcinoma (STAD) remains insufficiently clarified.

Methods

We applied large-scale bioinformatics interrogation of The Cancer Genome Atlas (TCGA) STAD cohort, combined with in vitro cellular assays and in vivo xenograft experiments, to explore both the biological significance and molecular mechanisms of miR-124-3p in STAD progression.

Results

MiR-124-3p expression was significantly downregulated in STAD tissues and correlated with advanced pathological stage, poor prognosis, and reduced survival outcomes. Functional investigations confirmed that miR-124-3p directly interacts with the 3'-UTR of the aryl hydrocarbon receptor (AHR) mRNA, suppressing its expression and inducing autophagy. This regulation led to impaired proliferation, migration, and invasiveness of STAD cells. Restoration of AHR expression reversed these tumor-suppressive effects. Moreover, in vivo delivery of miR-124-3p inhibited tumor growth and mitigated cancer-induced cachexia in nude mice.

Conclusion

These findings establish miR-124-3p as a key suppressor of STAD progression via AHR-mediated autophagy, underscoring its promise as both a diagnostic biomarker and a therapeutic candidate.

SUBMITTER: Wan Q 

PROVIDER: S-EPMC12866595 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature