lncRNA Lockd promotes cardiomyocyte proliferation via Eno1/beta-catenin/Myc axis
4 affiliations
- 1Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India
- 2National Institute of Plant Genome Research, New Delhi 110067, India
- 3Toxicology and Experimental Medicine Division, CSIR-Central Drug Research Institute, Lucknow 226031, India
- 4Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
Abstract
Neonatal mouse hearts exhibit a transient regenerative capacity that enables recovery from injury and certain pathological stresses; however, their response to pathological hypertrophic stimuli remains poorly defined. Here, we show that neonatal hearts within the regenerative window are protected from isoproterenol-induced pathological hypertrophy and maintain cardiac function, whereas hearts beyond this window develop hypertrophy and functional impairment. Resistance to hypertrophic stress during the regenerative phase was associated with robust cardiomyocyte proliferation, which was largely absent in the non-regenerative phase. Transcriptomic profiling identified the long non-coding RNA Lockd as the most upregulated transcript during the regenerative window, in an E2F1-dependent manner. Cardiomyocyte-specific AAV9-mediated overexpression of Lockd in non-regenerative neonatal hearts attenuated isoproterenol-induced hypertrophy, preserved cardiac function, and restored cardiomyocyte proliferative capacity. Mechanistically, Lockd directly interacted with and stabilized α-enolase (ENO1), leading to enhanced β-catenin stability, nuclear accumulation, and induction of the pro-proliferative target gene Myc. Consistently, Eno1 knockdown impaired β-catenin signaling, Myc expression, and cardiomyocyte proliferation. These findings identify Lockd as a key mediator of regenerative resistance to pathological hypertrophic stress in the neonatal heart.
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BibTeX
@article{prakash2026lncrna,
title = {{lncRNA Lockd promotes cardiomyocyte proliferation via Eno1/beta-catenin/Myc axis}},
author = {Shakti Prakash and Samprikta Kundu and Ayushi Devendrasingh Chaudhary and Sakshi Chaudhary and Chandan Kumar and Sunaina Kumari and Sandhya Singh and Babita Yadav and Anuj Kumar and V.M. Prajapati and Kumaravelu Jagavelu and Shailesh Kumar and Shashi Kumar Gupta},
journal = {Molecular therapy. Nucleic acids},
year = {2026},
month = oct,
doi = {10.1016/j.omtn.2026.103132},
url = {https://europepmc.org/article/PMC/PMC13717029},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - lncRNA Lockd promotes cardiomyocyte proliferation via Eno1/beta-catenin/Myc axis
AU - Shakti Prakash
AU - Samprikta Kundu
AU - Ayushi Devendrasingh Chaudhary
AU - Sakshi Chaudhary
AU - Chandan Kumar
AU - Sunaina Kumari
AU - Sandhya Singh
AU - Babita Yadav
AU - Anuj Kumar
AU - V.M. Prajapati
AU - Kumaravelu Jagavelu
AU - Shailesh Kumar
AU - Shashi Kumar Gupta
PY - 2026
DA - 2026/10/07
JO - Molecular therapy. Nucleic acids
DO - 10.1016/j.omtn.2026.103132
UR - https://europepmc.org/article/PMC/PMC13717029
AB - Neonatal mouse hearts exhibit a transient regenerative capacity that enables recovery from injury and certain pathological stresses; however, their response to pathological hypertrophic stimuli remains poorly defined. Here, we show that neonatal hearts within the regenerative window are protected from isoproterenol-induced pathological hypertrophy and maintain cardiac function, whereas hearts beyond this window develop hypertrophy and functional impairment. Resistance to hypertrophic stress during the regenerative phase was associated with robust cardiomyocyte proliferation, which was largely absent in the non-regenerative phase. Transcriptomic profiling identified the long non-coding RNA Lockd as the most upregulated transcript during the regenerative window, in an E2F1-dependent manner. Cardiomyocyte-specific AAV9-mediated overexpression of Lockd in non-regenerative neonatal hearts attenuated isoproterenol-induced hypertrophy, preserved cardiac function, and restored cardiomyocyte proliferative capacity. Mechanistically, Lockd directly interacted with and stabilized α-enolase (ENO1), leading to enhanced β-catenin stability, nuclear accumulation, and induction of the pro-proliferative target gene Myc. Consistently, Eno1 knockdown impaired β-catenin signaling, Myc expression, and cardiomyocyte proliferation. These findings identify Lockd as a key mediator of regenerative resistance to pathological hypertrophic stress in the neonatal heart.
SN - 2162-2531
ER -