Comparison of HIF1A-AS1 and HIF1A-AS2 in regulating HIF-1α and the osteogenic differentiation of PDLCs under hypoxia

Abstract

Hypoxia‑inducible factor‑1α (HIF‑1α) is essential for regulating the osteogenic differentiation of periodontal ligament cells (PDLCs). The regulatory mechanism of HIF‑1α transcription is still not clear. Recently, two long non‑coding RNAs, HIF1A antisense RNA 1 (HIF1A‑AS1) and HIF1A antisense RNA 2 (HIF1A‑AS2), were found to regulate HIF‑1α mRNA, but the regulatory mechanisms among HIF‑1α, HIF1A‑AS1 and HIF1A‑AS2 have not been well studied. We hypothesized that HIF1A‑AS1 and HIF1A‑AS2 play important roles in the osteogenic differentiation of PDLCs by regulating HIF‑1α. In the present study, we showed that expression levels of HIF1A‑AS1, HIF1A‑AS2, HIF‑1α and osteogenic biomarkers were time‑dependent under hypoxia. Even though both HIF1A‑AS1 and HIF1A‑AS2 were complementary to HIF‑1α mRNA, only HIF1A‑AS2 showed an inhibitory effect on HIF‑1α in PDLCs. Moreover, HIF‑1α had positive regulatory effects on HIF1A‑AS1 and HIF1A‑AS2. HIF‑1α promoted the osteogenic differentiation of PDLCs, and HIF1A‑AS2 had a negative effect on the osteogenic differentiation of PDLCs. Altogether, the present study revealed the complex relationships among HIF1A‑AS1, HIF1A‑AS2 and HIF‑1α, as well as their roles in regulating the osteogenic differentiation of PDLCs. These findings provide a theoretical basis for promoting periodontal tissue regeneration and repair during orthodontic tooth movement.

Comprehensive transcriptomic profiling reveals SOX7 as an early regulator of angiogenesis in hypoxic human endothelial cells

“…P-value = 5e-6) but not its own promoter or that of HIF1A-AS1 while both regions had consensus HIF binding sites and active chromatin marks ( Figure S7). Combined with our expression profiles, these observations suggest a feedback regulatory role for HIF1A-AS2 and/or EPAS1 in HIF1A expression as seen in periodontal ligament cells ( (38) and renal cell carcinoma and glioblastoma cells (39).…”

RETRACTED ARTICLE: Long non-coding RNA HIF1A-AS2 facilitates adipose-derived stem cells (ASCs) osteogenic differentiation through miR-665/IL6 axis via PI3K/Akt signaling pathway

“…HIF1A-AS2 has already been found upregulated in some cancers; its influence on maintenance of mesenchymal glioblastoma stem-like cells is noteworthy [11]. Chen et al revealed that HIF1A-AS1 and HIF1A-AS2 took part in periodontal ligament cell (PDLC) osteogenic differentiation which was regulated by hypoxia-inducible factor-1α (HIF-1α) [15]. It was primarily proved that HIF1A-AS1 played a role in PDLC osteogenic differentiation and it still needed further research in ASCs.…”

“…HIF1A-AS2 is a kind of lncRNA which facilitates several cancers, such as colorectal cancer, bladder cancer, and glioblastoma [10–12]; it is considered as a diagnostic biomarker of the development in differentiation between diverse breast cancer types [13], as well as an influence on other processes including HUVEC angiogenesis [14]. A recent study revealed that HIF1A-AS1 and HIF1A-AS2 played a role in regulating hypoxia-inducible factor-1α (HIF-1α) and further affected periodontal ligament cell (PDLC) osteogenic differentiation [15]. But the effect of HIF1A-AS2 on ASC osteogenic differentiation still needs more exploration.…”

Altered secretory and neuroprotective function of the choroid plexus in progressive multiple sclerosis

“…HIF1A-AS3 is one of the three antisense genes of HIF1A. Another antisense, HIF1A-AS2, is involved in the regulation of HIF-1ɑ [12,43]. HIF1A-AS2 mRNA was not significantly higher in the CP of progressive MS patients relative to that of controls, suggesting that HIF1A-AS3 may act as an upstream regulator of the hypoxia responses observed in our study.…”