Department of Intensive Care Unit, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Department of neurosurgery, Medical Center Hospital of QiongLai City, Chengdu, China.
Carcinogenesis. 2022 May 19;43(4):371-381. doi: 10.1093/carcin/bgac004.
Sepsis is characterized by a dysregulated inflammatory response. We aimed to explore the role of the long noncoding RNA urothelial carcinoma associated 1 (lncRNA UCA1)/enhancer of zeste homolog 2 (EZH2)/homeobox A1 (HOXA1) axis in sepsis-induced pneumonia. The sepsis rat models and RLE-6TN cellular sepsis-induced pneumonia models were established using ligation and puncture (CLP) and lipopolysaccharide (LPS). The expression of UCA1, EZH2, and HOXA1 in rat lung tissues and RLE-6TN cells was detected. Then, the CLP rats were respectively treated with lentivirus to upregulate or downregulate the expression of UCA1 and EZH2 to measure their roles in the pathology, apoptosis, inflammation and phosphorylated NF-κB p65(p-p65) levels in CLP rat lung tissues. UCA1 and EZH2 expression was upregulated or downregulated in LPS-induced RLE-6TN cells to explore their effects on cell viability, apoptosis, inflammation and p-p65 levels. The interactions among UCA1, EZH2, and HOXA1 were identified. UCA1 and EZH2 were upregulated whereas HOXA1 was downregulated in CLP rat lung tissues and LPS-induced RLE-6TN cells. Elevated UCA1 or increased EZH2 aggravated pathology and promoted apoptosis, inflammation and phosphorylated NF-κB p-65 levels in CLP rat lung tissues, and inhibited viability while facilitated apoptosis, inflammation and phosphorylated NF-κB p-65 levels in LPS-induced RLE-6TN cells. Silenced EZH2 reversed the effects of UCA1 elevation on sepsis-induced pneumonia. UCA1 suppressed HOXA1 expression through physically interacting with EZH2. UCA1 overexpression upregulates EZH2 to repress HOXA1 expression, thus aggravating the progression of sepsis-induced pneumonia, which could be alleviated by EZH2 inhibition.
脓毒症的特征是炎症反应失调。本研究旨在探讨长链非编码 RNA 尿路上皮癌相关 1（lncRNA UCA1）/增强子的组蛋白 2（EZH2）/同源盒 A1（HOXA1）轴在脓毒症性肺炎中的作用。通过结扎和穿刺（CLP）和脂多糖（LPS）建立脓毒症大鼠模型和 RLE-6TN 细胞脓毒症性肺炎模型。检测大鼠肺组织和 RLE-6TN 细胞中 UCA1、EZH2 和 HOXA1 的表达。然后，用慢病毒分别上调或下调 CLP 大鼠 UCA1 和 EZH2 的表达，以测量它们在 CLP 大鼠肺组织病理、细胞凋亡、炎症和磷酸化 NF-κB p65（p-p65）水平中的作用。用 LPS 诱导 RLE-6TN 细胞上调或下调 UCA1 和 EZH2 的表达，以探讨它们对细胞活力、细胞凋亡、炎症和 p-p65 水平的影响。鉴定 UCA1、EZH2 和 HOXA1 之间的相互作用。CLP 大鼠肺组织和 LPS 诱导的 RLE-6TN 细胞中 UCA1 和 EZH2 上调，而 HOXA1 下调。UCA1 或 EZH2 升高加重 CLP 大鼠肺组织病理，促进细胞凋亡、炎症和磷酸化 NF-κB p-65 水平升高，抑制细胞活力，促进 LPS 诱导的 RLE-6TN 细胞凋亡、炎症和磷酸化 NF-κB p-65 水平升高。沉默 EZH2 逆转了 UCA1 升高对脓毒症性肺炎的影响。UCA1 通过与 EZH2 相互作用抑制 HOXA1 表达。UCA1 过表达上调 EZH2 抑制 HOXA1 表达，从而加重脓毒症性肺炎的进展，EZH2 抑制可缓解。
