ArticleFrontiers in pharmacology2026
microRNA-15b modulates stress-induced premature senescence in chronic doxorubicin cardiomyopathy.
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Introduction: Doxorubicin (DOX) is the most widely used anthracycline in hematologic and solid tumors, whose clinical utility is constrained by dose-dependent cumulative cardiotoxicity that can progress to chronic heart failure. Although previously attributed to overt cardiomyocyte loss, emerging evidence indicates that stress-induced premature senescence (SIPS) constitutes the dominant mechanism of chronic cardiotoxicity at clinically relevant concentrations. SIPS is defined by permanent cell cycle arrest, activation of the p53/p21 and p16/Rb tumor suppressor axes, mitochondrial dysfunction, and a senescence-associated secretory phenotype (SASP) that sustains a pro-inflammatory myocardial milieu. Nevertheless, the post-transcriptional mechanisms that govern this process remain incompletely understood. Methods: The post-transcriptional regulation of DOX-induced SIPS was evaluated Results: Sublethal DOX treatment (0.1 μM) suppressed miR-15b expression by approximately 50% in NRVMs, resulting in post-transcriptional derepression of its mitochondrial target, SIRT4. This miR-15b loss triggered a multiparametric SIPS phenotype encompassing accumulation of γH2AX foci, p53/p21 and p16 activation, SASP induction (IL-6, IL-1β, Mcp-1 and Mmp13), lysosomal dysfunction (increased SA-β-Gal staining) and mitochondrial dysfunction. Prophylactic restoration of miR-15b via a synthetic mimetic selectively attenuated the p53/p21 axis, genomic damage foci, lysosomal dysfunction, mitochondrial dysfunction and SASP (IL-6 and IL-1β), without rescuing the p16/Rb pathway. In the female C57BL/6 chronic cardiotoxicity model, the cohort spontaneously stratified into animals completing the protocol (ND; 67%) and a premature death subgroup (PD; 33%). The PD subgroup exhibited the most profound myocardial miR-15b suppression and greater accumulation of SIPS markers, including γH2AX, p16, and reduced Lamin B. Notably, the SASP displayed distinct qualitative profiles between PD and ND animals, suggesting that SASP composition, rather than magnitude alone, determines the cardiotoxic outcome. Conclusion: Collectively, these findings position miR-15b as a key post-transcriptional regulator of DOX-induced SIPS in the cardiomyocyte, whose sustained loss associates with cardiotoxicity severity
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.