Description: Hypertrophic ligamentum flavum (LF) is a main cause responsible for lumbar spinal stenosis (LSS). Various miRNAs and circRNAs might be involved in these pathophysiological processes; however, their exact regulatory mechanisms remain unknown. The present study aimed to elucidate how circRNAs and miRNAs jointly regulate the pathogenesis of LF and LSS, especially focusing on circPDK1 (hsa_circ_0057105), a circRNA which exhibited significantly differential expression in LF tissues between lumbar disc herniation and LSS patients. miRNA-4731, a pivotal target of circPDK1, was suggested by bioinformatics analyses. Further transcriptome analysis in silico prediction potentiated circPDK1-miR-4731-TNXB as a pathway for investigation. Afterward, dual luciferase reporter assay system was performed to validate the direct interactions between these molecules. Colony formation, wound-healing and MTT assays were used for estimating cell proliferation and migration. Protein expresion levels were evaluated using Western-blotting.The expression of TNXB was verified using immunohistochemistry (IHC). Luciferase assays confirmed direct interactions between circPDK1/miR-4731-5p or miR-4731-5p/TNXB. Overexpression of circPDK1 facilitated multiple hypertrophy-promoting properties of LF including proliferation, migration and the expression of fibrosis-related protein (α-SMA, LOXL2, Collagen I and MMP-2); similar results were obtained regarding TNXB whereas miR-4731-5p showed opposite effects. Consistently, circPDK1 induced-expression of TNXB was revealed by IHC; contrary results were observed with miR-4731-5p. Intriguingly, co-overexpression of miR-4731-5p partially reversed the proliferative and fibrosis-prompting effects mediated by overexpression of circPDK1 or TNXB. We propose circPDK1-miR-4731-TNXB as a regulatory axis in LF hypertrophy, which might shed a light on in-depth research of LSS, as well as providing a novel therapeutic target for LF hypertrophy-induced LSS.

Data type: Raw sequence reads

Sample scope: Monoisolate

Relevance: Medical

Release date: 2021-09-10

Last updated: 2021-09-09

Data size: 85.35GB