Department of Critical Care Medicine, Zibo Central Hospital, No. 10, Shanghai Road, Zhangdian District, Zibo City, Shangdong Province, 255000, China.
Funct Integr Genomics. 2024 Aug 20;24(5):140. doi: 10.1007/s10142-024-01411-1.
Acute pancreatitis (AP) is an inflammatory disease of the pancreas and the main cause of hospital admissions for gastrointestinal diseases. Here, the work studied the circular RNA DTNB/microRNA-485-5p/MCL1 axis in AP and hoped to unravel the related mechanism. Caerulein exposure replicated an AP model in AR42J cells, and caerulein-mediated expression of circDTNB, miR-485-5p, and MCL1 was recorded. After exposure, cells were intervened with transfection plasmids and tested for LDH release, apoptosis, and inflammation. To determine the interwork of circDTNB, miR-485-5p, and MCL1, prediction results and verification experiments were conducted. Caerulein exposure reduced circDTNB and MCL1, while elevated miR-485-5p levels in AR42J cells. Upregulating circDTNB protected AR42J cells from caerulein-induced LDH cytotoxicity, apoptosis, and inflammation, but circDTNB upregulation-induced protections could be muffled by inhibiting MCL1. On the contrary, downregulating circDTNB further damaged AR42J cells under caerulein exposure, however, this phenomenon could be partially rescued after silencing miR-485-5p. miR-485-5p was mechanistically verified to be a target of circDTNB to mediate MCL1. Overall, the circDTNB/miR-485-5p/MCL1 axis protects inflammatory response and apoptosis in caerulein-exposed AR42J cells, promisingly identifying circDTNB as a novel molecule for AP treatment.
急性胰腺炎 (AP) 是一种胰腺炎症性疾病,也是胃肠道疾病住院的主要原因。在这里,我们研究了 AP 中的环状 RNA DTNB/miR-485-5p/MCL1 轴,希望阐明其相关机制。雨蛙肽暴露可复制 AR42J 细胞中的 AP 模型,并记录雨蛙肽介导的 circDTNB、miR-485-5p 和 MCL1 的表达。暴露后,用转染质粒干预细胞,并测试 LDH 释放、细胞凋亡和炎症。为了确定 circDTNB、miR-485-5p 和 MCL1 的相互作用,进行了预测结果和验证实验。雨蛙肽暴露降低了 circDTNB 和 MCL1 的水平,而增加了 miR-485-5p 的水平。上调 circDTNB 可保护 AR42J 细胞免受雨蛙肽诱导的 LDH 细胞毒性、细胞凋亡和炎症,但上调 circDTNB 诱导的保护作用可被抑制 MCL1 所掩盖。相反,在雨蛙肽暴露下下调 circDTNB 进一步损害了 AR42J 细胞,但沉默 miR-485-5p 后可部分挽救这种现象。miR-485-5p 被机制验证为 circDTNB 介导 MCL1 的靶标。总的来说,circDTNB/miR-485-5p/MCL1 轴可保护雨蛙肽暴露的 AR42J 细胞中的炎症反应和细胞凋亡,有望将 circDTNB 鉴定为治疗 AP 的新型分子。