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Long non-coding RNAs (lncRNAs) play an important role in gene regulation and are involving in diverse cellular processes. However, their roles in reprogramming of gene expression profiles during lineage commitment and maturation of mesenchymal stem cells (MSCs) remain poorly understood. In the current study, we characterize the expression of a lncRNA, HoxA-AS3, during the differentiation of MSCs. We showed that HoxA-AS3 is increased upon adipogenic induction of MSCs, while HoxA-AS3 remains unaltered during osteogenic induction. Silencing of HoxA-AS3 in MSCs resulted in decreased adipogenesis and expression of adipogenic markers, PPARG, CEBPA, FABP4 and ADIPOQ. Conversely, knockdown of HoxA-AS3 expression in MSCs exhibited an enhanced osteogenesis and osteogenic markers expression, including RUNX2, SP7, COL1A1, IBSP, BGLAP and SPP1. Mechanistically, HoxA-AS3 interacts with Enhancer Of Zeste 2 (EZH2) and is required for H3 lysine-27 trimethylation (H3K27me3) of key osteogenic transcription factor Runx2. Our data reveal that HoxA-AS3 acts as an epigenetic switch that determines the lineage specification of MSC.
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http://dx.doi.org/10.18632/oncotarget.11538 | DOI Listing |
Nature
September 2025
Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Cancer-associated muscle wasting is associated with poor clinical outcomes, but its underlying biology is largely uncharted in humans. Unbiased analysis of the RNAome (coding and non-coding RNAs) with unsupervised clustering using integrative non-negative matrix factorization provides a means of identifying distinct molecular subtypes and was applied here to muscle of patients with colorectal or pancreatic cancer. Rectus abdominis biopsies from 84 patients were profiled using high-throughput next-generation sequencing.
View Article and Find Full Text PDFNat Commun
September 2025
Guangdong Provincial Key Laboratory of Bioengineering Medicine & National Engineering Research Center of Genetic Medicine, Department of Cell Biology and Institute of Biomedicine, Jinan University, Huang-Pu Avenue West 601, Guangzhou, 510632, China.
Gene
September 2025
Institute of Physiology, Medical School, University of Pécs H-7624 Pécs, Hungary. Electronic address:
In this edition of Gene's "Editor's Corner" we summarize the complex interactions of different molecular mechanisms behind the pathogenesis of neonatal hypoxic-ischemic encephalopathy (HIE). The topic is relevant, as the therapeutic options for HIE are limited, it is important to have as much knowledge as possible about the molecular processes underlying the disease. In the recent issue of Gene (Gene 952, 2025, 149363), Wang et al.
View Article and Find Full Text PDFStem Cell Reports
September 2025
Department of Physiology, Anatomy and Genetics, University of Oxford, OX1 3PT Oxford, UK. Electronic address:
Neural stem cells (NSCs) in the subventricular zone (SVZ) produce neurons throughout life. However, the epigenetic mechanisms that maintain NSCs and control neurogenesis remain unclear. We previously showed the long non-coding RNA (lncRNA) Paupar and KAP1 transcription co-factor control neuroblastoma cell growth.
View Article and Find Full Text PDFMutat Res Rev Mutat Res
September 2025
Institute of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address:
To maintain genomic stability, cells have evolved complex mechanisms collectively known as the DNA damage response (DDR), which includes DNA repair, cell cycle checkpoints, apoptosis, and gene expression regulation. Recent studies have revealed that long non-coding RNAs (lncRNAs) are pivotal regulators of the DDR. Beyond their established roles in recruiting repair proteins and modulating gene expression, emerging evidence highlights two particularly intriguing functions.
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