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

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.

Role of microRNAs in Diabetes-Associated Periodontitis: A Scoping Review

“…In PD patients with DM, it induces oxidative stress and inflammation by inhibiting AKT phosphorylation and upregulating the expression of phosphatase and tensin homolog through sponge miRNA-508-3p. [ 33 ]…”

“…An additional 33 papers were excluded after reviewing the titles and abstracts of the remaining 47 papers for the following reasons:1 study involved women with gestational diabetes, 2 studies involved patients with COVID-19, 23 were not relevant to the search question, 2 were not in English, and 5 were literature reviews. Finally, the review included full texts of four in vivo studies in humans,[ 15 , 22 , 23 , 24 ] six studies in animals,[ 25 , 26 , 29 , 31 , 32 , 34 ] four ex vivo studies,[ 27 , 28 , 30 , 33 ] and two studies conducted in vitro experiments followed by assessment in animal models. [ 29 , 32 ] The study selection process is shown in the PRISMA-scR flow diagram [ Figure 1 ].…”

“…[ 31 ] In a few studies, macrophages and human periodontal ligament cells (hPDLCs) were cultured to evaluate the role of miRNA in DM-associated PD. [ 26 , 30 , 32 ] Various miRNAs investigated in these studies were miRNA-126,[ 27 , 32 ] miRNA-147,[ 25 ] miRNA-31,[ 26 ] miRNA-25-3p,[ 31 ] miRNA-508-3p,[ 33 ] SIRT6-miR-216/217 axis,[ 34 ] miRNA-214,[ 28 ] miRNA124-3p,[ 29 ] and miRNA-221 and -222. [ 30 ]…”