LncRNA NEAT1/miR-146a-5p Axis Restores Normal Angiogenesis in Diabetic Foot Ulcers by Targeting mafG

Author:

Architha TCA1ORCID,Juanitaa George Raj1,Vijayalalitha Ramanarayanan1ORCID,Jayasuriya Ravichandran1,Athira Gopinathan2,Balamurugan Ramachandran2,Ganesan Kumar3ORCID,Ramkumar Kunka Mohanram1ORCID

Affiliation:

1. Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Chengalpattu Dt., Tamil Nadu, India

2. SRM Medical Hospital and Research Centre, SRM Institute of Science and Technology, Kattankulathur 603 203, Chengalpattu Dt., Tamil Nadu, India

3. School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong 999077, China

Abstract

Non-healing lesions in diabetic foot ulcers are a significant effect of poor angiogenesis. Epigenetic regulators, mainly lncRNA and miRNA, are recognized for their important roles in disease progression. We deciphered the regulation of lncRNA NEAT1 through the miR-146a-5p/mafG axis in the progression of DFU. A lowered expression of lncRNA NEAT1 was associated with dysregulated angiogenesis through the reduced expression of mafG, SDF-1α, and VEGF in chronic ulcer subjects compared to acute DFU. This was validated by silencing NEAT1 by SiRNA in the endothelial cells which resulted in the transcriptional repression of target genes. Our in silico analysis identified miR-146a-5p as a potential target of lncRNA NEAT1. Further, silencing NEAT1 led to an increase in the levels of miR-146a-5p in chronic DFU subjects. This research presents the role of the lncRNA NEAT1/miR-146a-5p/mafG axis in enhancing angiogenesis in DFU.

Funder

Indian Council of Medical Research

Publisher

MDPI AG

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