Integrative Analysis of ceRNA Networks in human periodontal ligament stem cells under hypoxia

Oral Dis. 2021 Dec 7. doi: 10.1111/odi.14096. Online ahead of print.

Abstract

Objective: This study aims to investigate the regulatory effect of hypoxia on human periodontal ligament stem cells (PDLSCs) through RNA sequencing (RNA SEQ). Human PDLSCs were cultured in normoxia (20% O2 ) or hypoxia (2% O2 ).

Material and methods: Total RNA was extracted and sequenced. The expression profiles of circRNAs, lncRNAs, and miRNAs were determined, and the lncRNA/circRNA-miRNA-mRNA networks were analyzed.

Results: In total, 15 miRNAs, 449 lncRNAs, and 53 circRNAs were differentially expressed. Among them, 21 circRNAs, 262 lncRNAs, 5 miRNAs, and 5 mRNAs were selected to construct competing endogenous RNA (ceRNA) networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out to explore potential related pathways and regulatory functions. Several ceRNA axes (lncRNA-FTX/circRNA-FAT1-hsa-miR-4781-3p-SMAD5 and circRNA LPAR1-hsa-miR-342-3p-ADAR) may provide a theoretical basis on the study of osteogenic differentiation of PDLSCs under hypoxia.

Conclusion: This study revealed that the expression profiles of circRNAs, lncRNAs, and miRNAs had changed significantly in PDLSCs cultured in 2% O2 ; specific circRNAs/lncRNAs may play a competitive role in the differentiation of PDLSCs.

Keywords: competing endogenous RNAs network; gene expression; human periodontal ligament stem cells; hypoxia; osteogenic differentiation.