Coordinated regulation of nuclear integrity and STING trafficking by miR-30d suppresses innate immunity in breast cancer
Year: 2026
Type: article
Abstract: Immune evasion is a key driver of tumour evolution and a major barrier to effective cancer therapy, frequently arising through suppression of the cytosolic DNA-sensing cGAS–STING pathway. Here, we identify miR-30d as a post-transcriptional regulator that operates at two mechanistically distinct levels in breast cancer. Upstream, miR-30d maintains nuclear envelope integrity via the LATS2–YAP–Lamin B1 axis, limiting nuclear rupture, genomic damage, and cytosolic DNA leakage that activate cGAS. In parallel, miR-30d impairs STING trafficking from the endoplasmic reticulum to the Golgi, restraining TBK1 activation and downstream signal propagation. Inhibition of miR-30d restores cGAS activation and STING trafficking, enhancing type I interferon response and antitumour immunity, suppressing tumour growth, and improving responsiveness to immune checkpoint blockade. These findings define a miR-30d-regulated nuclear envelope–Golgi axis that restrains innate immune surveillance, and suggest miR-30d inhibition as a potential strategy to overcome immune evasion. Breast cancer cells use a short RNA molecule, miR-30d, to hide from immune attack by muting a cellular DNA-sensing alarm system. Blocking miR-30d reactivates the alarm, slows tumour growth and boosts immunotherapy.
Source: Nature Communications
Authors: Serena Torrini, Suvarna Chatterjee, Alessandra Rustighi, Federica Di Camillo, Valeria Cancila, Rebecca Bertolio, Luca Triboli, Galina Beznoussenko, Zeno Lavagnino, Anna Renzi, Mariano Martelli, Alessia Mattivi, Luca L. Fava, Giulia Canarutto, Silvano Piazza, Cesare Valenti, Claudio Tripodo, Giorgio Scita, Fiamma Mantovani, Giannino Del Sal
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W7223472423
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