Pan Zhaohui, Zhang Li, Hu Jing
Department of Gastroenterology, Shijiazhuang People's Hospital, Hebei Medical University, Shijiazhuang, Hebei, China.
Medicine (Baltimore). 2024 Dec 6;103(49):e40568. doi: 10.1097/MD.0000000000040568.
Duodenal ulcer (DU) represents a clinical manifestation and disease state that occurs when the mucosal surface of the duodenum is damaged. The processes of autophagy and apoptosis have been linked to the development of DU, yet the precise roles they play remain unclear. This study aimed to investigate the expression and mechanism of action of microRNAs (miRNA)-137 (miR-137) in DU.
Dysregulated miRNAs and targeted genes were identified from the Gene Expression Omnibus database, and the immune cell infiltration levels were analyzed using CIBERSORT. To confirm the targeting of the miRNAs, we conducted dual luciferase reporter assays in vitro. The detection of cell apoptosis was conducted using flow cytometry. Moreover, quantitative reverse transcription polymerase chain reaction, cell counting kit-8, and Western blot were employed to ascertain the levels of autophagy- and apoptosis-related proteins.
Bioinformatics analysis identified 5 miRNAs, with miR-137 showing the most pronounced dysregulation. Its target gene, BNIP3L, was subsequently identified. In vitro experiments confirmed that miR-137 targeted BNIP3L. The upregulation of miR-137 expression in HIEC-6 cells resulted in the inhibition of BNIP3L expression, a reduction in autophagy, and an increase in apoptosis. A reduction in the expression of miR-137 would have the opposite effect.
miR-137 is upregulated in DU patients and contributes to ulcer progression by inhibiting BNIP3L, reducing autophagy, and promoting apoptosis. Targeting miR-137 could provide a novel therapeutic strategy for DU management.
十二指肠溃疡（DU）是十二指肠黏膜表面受损时出现的一种临床表现和疾病状态。自噬和凋亡过程与DU的发生发展有关，但其确切作用尚不清楚。本研究旨在探讨微小RNA（miRNA）-137（miR-137）在DU中的表达及作用机制。
从基因表达综合数据库中鉴定失调的miRNA和靶向基因，并使用CIBERSORT分析免疫细胞浸润水平。为了证实miRNA的靶向作用，我们在体外进行了双荧光素酶报告基因检测。使用流式细胞术检测细胞凋亡。此外，采用定量逆转录聚合酶链反应、细胞计数试剂盒-8和蛋白质免疫印迹法来确定自噬和凋亡相关蛋白的水平。
生物信息学分析鉴定出5种miRNA，其中miR-137的失调最为明显。随后鉴定出其靶基因BNIP3L。体外实验证实miR-137靶向BNIP3L。HIEC-6细胞中miR-137表达上调导致BNIP3L表达受到抑制，自噬减少，凋亡增加。miR-137表达降低则会产生相反的效果。
DU患者中miR-137上调，通过抑制BNIP3L、减少自噬和促进凋亡促进溃疡进展。靶向miR-137可为DU的治疗提供一种新的策略。
