MicroRNA-138 regulation promotes the efficacy of oncolytic herpes virus G47Δ for malignant brain tumor therapy.

ABSTRACT: G47Δ, a third-generation oncolytic herpes simplex virus type 1, is a promising therapeutic agent for malignant glioma. We investigated whether inhibition of host microRNA-138 (miR-138), a regulator of the viral immediate-early protein ICP0, could enhance its efficacy. In vitro, miR-138 suppression increased viral protein expression, progeny virus production, and cytotoxicity in human glioblastoma and murine Neuro2a cells, whereas overexpression suppressed these effects. Neuro2a cells stably silenced for miR-138 showed tumor regression in 9 of 13 syngeneic mice, but not in athymic mice or following CD8⁺ T cell depletion, indicating dependence on adaptive immunity. Mechanistically, miR-138 directly targeted signal transducer and activator of transcription 1 (STAT1) mRNA: It

SUBMITTER: Kanayama S 

PROVIDER: S-EPMC12800491 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature