长链非编码 RNA-CCAT1/miR-152-3p 通过调节 ERK 信号通路参与 CSE 诱导的 HBE 细胞炎症。
LncRNA-CCAT1/miR-152-3p is involved in CSE-induced inflammation in HBE cells via regulating ERK signaling pathway.
机构信息
Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China; Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China.
Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China; Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China.
出版信息
Int Immunopharmacol. 2022 Aug;109:108818. doi: 10.1016/j.intimp.2022.108818. Epub 2022 May 3.
Emerging studies have noted that dysregulated long non-coding RNAs (lncRNAs) are implicated in the pathological processes of chronic obstructive pulmonary disease (COPD). LncRNA colon cancer-associated transcript 1 (CCAT1) plays well-defined roles in the inflammatory progression. The study aims to figure out the effect and regulatory mechanism of CCAT1 in the cigarette smoke induced inflammation in COPD. The results showed that CCAT1 was highly expressed in lung tissues of smokers with COPD compared with never-smokers without COPD. In human bronchial epithelial (HBE) cells, cigarette smoke extract (CSE) treatment led to an increase in CCAT1 expression in a dose- and time- dependent manner. Functional experiments showed that knockdown of CCAT1 amelioratedCSE-inducedinflammation. Mechanistically, CCAT1 directly targeted miR-152-3p, and miR-152-3p overexpression reversed the pro-inflammatory effects of CCAT1 on HBE cells. Subsequently, miR-152-3p was found to regulate ERK signaling pathway. PD98059, an ERK specific inhibitor, reversed miR-152-3p knockdown mediated inflammation in HBE cells. In addition, CCAT1 acted as a sponge for miR-152-3p to positively regulate ERK signaling pathway. Overall, current findings suggest that CCAT1 promoted inflammation by activating ERK signal pathway via sponging miR-152-3p in CSE-treated HBE cells. These results may provide a novel therapeutic target for alleviating cigarette smoke mediated airway inflammation.
新兴研究表明，失调的长非编码 RNA（lncRNA）与慢性阻塞性肺疾病（COPD）的病理过程有关。lncRNA 结肠癌相关转录物 1（CCAT1）在炎症进展中发挥明确作用。本研究旨在探讨 CCAT1 在 COPD 患者香烟烟雾诱导的炎症中的作用及其调控机制。结果表明，与无 COPD 的从不吸烟者相比，COPD 吸烟者的肺组织中 CCAT1 表达水平较高。在人支气管上皮（HBE）细胞中，香烟烟雾提取物（CSE）处理以剂量和时间依赖的方式导致 CCAT1 表达增加。功能实验表明，敲低 CCAT1 可改善 CSE 诱导的炎症。机制上，CCAT1 直接靶向 miR-152-3p，miR-152-3p 的过表达逆转了 CCAT1 对 HBE 细胞的促炎作用。随后，发现 miR-152-3p 调节 ERK 信号通路。ERK 特异性抑制剂 PD98059 逆转了 miR-152-3p 敲低介导的 HBE 细胞炎症。此外，CCAT1 作为 miR-152-3p 的海绵体，通过正向调节 ERK 信号通路发挥作用。总之，目前的研究结果表明，CCAT1 通过在 CSE 处理的 HBE 细胞中海绵吸附 miR-152-3p 来激活 ERK 信号通路，从而促进炎症。这些结果可能为减轻香烟烟雾介导的气道炎症提供新的治疗靶点。
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