Editorial Expression of Concern: MicroRNA-133 controls cardiac hypertrophy

Cardiac hypertrophy is a key pathological step in the progression of heart failure, and researchers have long sought to elucidate its molecular regulatory networks. Around 2007, the role of microRNAs in this field gradually emerged: studies showed that miR-1 and miR-133 play important roles in cardiomyocyte proliferation, differentiation, and hypertrophic growth, and that their expression profiles were broadly altered in agonist-induced hypertrophic cardiomyocytes and pressure-overloaded hearts ^[4]; contemporaneous work also demonstrated that the cardiac-specific miR-208 is required for stress-dependent cardiac growth and the regulation of gene expression ^[3]. Against this backdrop, Carè et al. published a study in Nature Medicine showing that miR-133 and miR-1 were downregulated in mouse and human models of cardiac hypertrophy, that overexpression in vitro suppressed hypertrophy, whereas inhibition of miR-133 with "decoy" sequences or antagomirs significantly induced hypertrophy, and identified target molecules including RhoA, Cdc42, and Nelf-A/WHSC2 ^[2]. This paper has been repeatedly cited in subsequent reviews and became one of the foundational works establishing miR-133's role in cardiac remodeling research ^[1]. Later studies revealed a mutual inhibitory relationship between miR-133 and calcineurin ^[5], and that miR-133 and miR-30 jointly regulate connective tissue growth factor, contributing to cardiac matrix remodeling ^[6].

However, this highly influential paper, published on April 29, 2007, now faces integrity-related concerns. According to PubMed records, the paper has been cited 2339 times ^[7]. On October 28, 2026, the Nature Medicine editors issued an Editorial Expression of Concern, noting problems with the northern blot images in Figure 1c and Figure S2c. Specifically, bands 1 and 2 of the ventricle in Figure 1 are highly similar on both the miR-133 and tRNAMet membranes, and band 1 of the miR-133 atrium is highly similar to ventricle bands 1 and 2; in Figure S2c, ventricle bands 1 and 2 for miR-1 and tRNAMet are also highly similar. Because of the passage of time, the original data are no longer available, and the editors advise readers to interpret these data with caution.

The authors' responses have been inconsistent. Ten authors—Alessandra Carè, Daniele Catalucci, Federica Felicetti, Désirée Bonci, Patrizia Segnalini, Leonardo Elia, Morten Høydal, Kirk Peterson, Carlo Croce, and corresponding author Gianluigi Condorelli—disagreed with the Editorial Expression of Concern; the publisher could not reach Patrizia Segnalini; one of the corresponding authors, Cesare Peschle, has passed away; the remaining authors did not respond to any correspondence from the editors or the publisher.

The significance of this event lies in the fact that the questioned images constitute the original evidence supporting the core conclusion that miR-133 and miR-1 expression changes in hypertrophic myocardium ^[2]. The doubts about their reliability will prompt the field to re-examine the large body of subsequent research built on the framework that miR-133 regulates hypertrophy ^[1][5][6]. At present, the Editorial Expression of Concern is not a retraction, and whether the original conclusions hold remains undetermined; moreover, the absence of original data makes independent verification impossible. How this issue will affect the overall body of evidence in this research direction remains to be seen.