Circular RNA hsa_circ_0084054 promotes the progression of periodontitis with diabetes via the miR‐508‐3p/PTEN axis

牙周炎 炎症 化学 牙周纤维 牙龈卟啉单胞菌 氧化应激 基因沉默 PTEN公司 分子生物学 癌症研究 细胞凋亡 医学 免疫学 内科学 生物 PI3K/AKT/mTOR通路 生物化学 基因 牙科
作者
Linlin He,Chengcheng Liu,Yiying Liu,Guoping Cheng,Ping Zhang,Shujuan Guo,Yi Ding
出处
期刊:Journal of Periodontal Research [Wiley]
卷期号:58 (4): 827-840 被引量:3
标识
DOI:10.1111/jre.13141
摘要

Abstract Background and Objective Diabetes is an important risk factor for periodontitis, and circular RNA (circRNA) may play an important role in aggravating inflammation and accelerating disease progression by regulating miRNA/mRNA. This study aimed to investigate the role and mechanism of the hsa_circ_0084054/miR‐508‐3p/PTEN axis in the progression of periodontitis with diabetes. Methods First, circRNA sequencing was used to screen the differentially expressed circRNAs of periodontal ligament cells (PDLCs) treated with high glucose and/or Porphyromonas gingivalis lipopolysaccharide (LPS) in vitro, and the overtly differentially expressed hsa_circ_0084054 was selected and was also verified in periodontal ligament (PDL) tissue from periodontitis patients with diabetes. Then, its ring structure was tested by Sanger sequencing, RNase R, and actinomycin D assays. The bioinformatics analysis, dual luciferase reporter assay, and RIP assay were used to explore the interaction of hsa_circ_0084054/miR‐508‐3p/PTEN axis, whose effects on inflammation, oxidative stress, and apoptosis of PDLCs were evaluated through the measurement of inflammatory factors, reactive oxygen species (ROS), total superoxide dismutase (SOD), malondialdehyde (MDA), and Annexin V/PI assay. Results By high‐throughput sequencing, it was found that hsa_circ_0084054 was significantly increased in HG + LPS group compared with control group and LPS group, which was also verified in periodontal ligament (PDL) tissue from periodontitis patients with diabetes. Silencing hsa_circ_0084054 in PDLCs decreased the expression of inflammatory factors (IL‐1β, IL‐6, TNF‐α), the levels of ROS and MDA, and the proportion of apoptotic cells; conversely, SOD activity was enhanced. In addition, we found that hsa_circ_0084054 could up‐regulate the expression of PTEN through sponge miR‐508‐3p to inhibit AKT phosphorylation, finally trigger the aggravation of oxidative stress and inflammation in periodontitis patients with diabetes. Conclusion hsa_circ_0084054 can aggravate inflammation and promote the progression of periodontitis with diabetes by regulating miR‐508‐3p/PTEN signaling axis, which may serve as a new target for the intervention of periodontitis with diabetes.
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