环状 RNA-UBE2G1 通过 miR-373/HIF-1a 轴调控 LPS 诱导的骨关节炎。
CircRNA-UBE2G1 regulates LPS-induced osteoarthritis through miR-373/HIF-1a axis.
机构信息
Department of Orthopedics, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University , Zhengzhou, China.
出版信息
Cell Cycle. 2020 Jul;19(13):1696-1705. doi: 10.1080/15384101.2020.1772545. Epub 2020 May 31.
UNLABELLED
Osteoarthritis (OA) is a very common chronic and degenerative joint disease characterized by persistent destruction of articular cartilage. Recently, increasing evidence showed that circular RNAs (circRNAs) play critical roles in OA progression. However, the functions of circRNAs in OA and their underlying mechanisms of action remain unclear. In the present study, the expression levels of circRNA-UBE2G1 and HIF-1a were significantly increased in OA tissues, whereas miR‑373 expression was downregulated. Function assays showed that circRNA-UBE2G1 inhibition reduced the effects of LPS on C28/I2 cells viability and apoptosis. In terms of mechanism, we revealed that circRNA-UBE2G1 binds to miR‑373 as competing endogenous RNAs (ceRNAs). HIF-1a might act as a target of miR‑373. Moreover, miR‑373 suppression or HIF-1a overexpression restored the effects of circRNA-UBE2G1 downregulation on LPS-induced chondrocytes injury. Collectively, our data suggest that circRNA-UBE2G1 facilitates the progression in the LPS-induced OA cell model via regulating the miR‑373/HIF-1a axis.
ABBREVIATIONS
OA: Osteoarthritis; Circular RNAs; miRNAs: MicroRNAs; Mut: Mutant; WT: Wild type; UTR: Untranslated region.
未加标签
骨关节炎（OA）是一种非常常见的慢性退行性关节疾病，其特征为关节软骨持续破坏。最近，越来越多的证据表明环状 RNA（circRNA）在 OA 进展中发挥关键作用。然而，circRNA 在 OA 中的功能及其作用机制尚不清楚。在本研究中，OA 组织中 circRNA-UBE2G1 和 HIF-1a 的表达水平显著升高，而 miR-373 的表达水平下调。功能分析表明，circRNA-UBE2G1 抑制降低了 LPS 对 C28/I2 细胞活力和凋亡的影响。就机制而言，我们揭示 circRNA-UBE2G1 作为竞争性内源 RNA（ceRNA）与 miR-373 结合。HIF-1a 可能是 miR-373 的靶标。此外，miR-373 抑制或 HIF-1a 过表达恢复了 circRNA-UBE2G1 下调对 LPS 诱导的软骨细胞损伤的作用。总之，我们的数据表明，circRNA-UBE2G1 通过调节 miR-373/HIF-1a 轴促进 LPS 诱导的 OA 细胞模型中的进展。
缩写
OA：骨关节炎；环状 RNA；miRNAs：MicroRNAs；Mut：突变型；WT：野生型；UTR：非翻译区。
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