CircRNA_0026344 via miR-21 is involved in cigarette smoke-induced autophagy and apoptosis of alveolar epithelial cells in emphysema
CircRNA_0026344 via miR-21 is involved in cigarette smoke-induced autophagy and apoptosis of alveolar epithelial cells in emphysema
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CircRNA_0026344通过miR-21参与香烟烟雾诱导的肺气肿肺泡上皮细胞自噬和凋亡
DOI：
10.1007/s10565-021-09654-5
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发表时间：
2021-09-15
影响因子：
6.1
通讯作者：
Liu, Qizhan
中科院分区：
文献类型：
--
作者：
Zhao, Jing;Xia, Haibo;Liu, Qizhan
香烟烟雾（CS）是室内空气污染的主要来源，是肺气肿的主要危险因素，细胞自噬异常与肺气肿的发病有关。环状rna （circRNAs）通过充当microRNA （miRNA）海绵来影响mrna的表达，但它们在肺气肿进展中的作用尚未确定。在本研究中，CS作用于肺泡上皮细胞，导致miR-21、p-ERK和cleaved-caspase 3水平升高，导致circRNA_0026344和PTEN水平降低，从而诱导自噬和凋亡。miR-21抑制PTEN的表达，PTEN参与自噬和凋亡的调控。此外，在肺泡上皮细胞中，circRNA_0026344的过表达阻断了香烟烟雾提取物（CSE）诱导的自噬和凋亡，但这种阻断可以通过模拟物上调miR-21而逆转。这些结果表明，在肺泡上皮细胞中，CS降低了circRNA_0026344的水平，从而使miR-21抑制miR-21的靶点PTEN，进而激活ERK，从而促进自噬和凋亡，导致肺气肿。因此，对于肺气肿，circRNA_0026344通过海绵miR-21调控PTEN/ERK轴，这与cs诱导的肺泡上皮细胞自噬和凋亡有关。总之，本研究确定了一种新的cs致肺气肿机制，为cs致肺气肿的诊断和治疗提供了有用的信息。
Cigarette smoke (CS), a main source of indoor air pollution, is a primary risk factor for emphysema, and aberrant cellular autophagy is related to the pathogenesis of emphysema. Circular RNAs (circRNAs) affect the expression of mRNAs via acting as microRNA (miRNA) sponges, but their role in emphysema progression is not established. In the present investigation, CS, acting on alveolar epithelial cells, caused higher levels of miR-21, p-ERK, and cleaved-caspase 3 and led to lower levels of circRNA_0026344 and PTEN, which induced autophagy and apoptosis. miR-21 suppressed the expression of PTEN, which was involved in the regulation of autophagy and apoptosis. Further, in alveolar epithelial cells, overexpression of circRNA_0026344 blocked cigarette smoke extract (CSE)-induced autophagy and apoptosis, but this blockage was reversed by upregulation of miR-21 with a mimic. These results demonstrated that, in alveolar epithelial cells, CS decreases circRNA_0026344 levels, which sponge miR-21 to inhibit the miR-21 target, PTEN, which, in turn, activates ERK and thereby promotes autophagy and apoptosis, leading to emphysema. Thus, for emphysema, circRNA_0026344 regulates the PTEN/ERK axis by sponging miR-21, which is associated with the CS-induced autophagy and apoptosis of alveolar epithelial cells. In sum, the present investigation identifies a novel mechanism for CS-induced emphysema and provides information useful for the diagnosis and treatment of CS-induced emphysema.