Sui Rongcui, Shi Wei, Han Shuhui, Fan Xintai, Zhang Xianzhao, Wang Na, Zhang Hao, Xu Anting, Liu Chengcheng
Department of Otolaryngology, The Second Hospital, Cheeloo College of Medicine, Shandong University, 274 Beiyuan Road, Jinan, Shandong, China; National Health Commission Key Laboratory of Otorhinolaryngology, The Second Hospital, Cheeloo College of Medicine, Shandong University, 274 Beiyuan Road, Jinan, Shandong, China.
Department of Otolaryngology, Zhoucun District People's Hospital, 72 Mianhua Shi Road, Zibo, Shandong, China.
Mol Immunol. 2022 Jan;141:236-245. doi: 10.1016/j.molimm.2021.11.017. Epub 2021 Dec 4.
MicroRNAs (miRNAs) play important roles in the regulation of cell proliferation, differentiation, apoptosis, and inflammatory responses. MiR-142-5p is an important inflammation-associated miRNA, whose abnormal expression has been associated with a variety of inflammation-related diseases. However, the role and signaling pathways targeted by miR-142-5p in acquired middle ear cholesteatoma (AMEC) have not been fully elucidated. Cyclin-dependent kinase 5 (CDK5), a special member of the CDK family compared with classic cyclins that plays a critical role in the inflammatory response. In this study, we investigated the roles of miR-142-5p and CDK5 in inflammatory responses in AMEC. Our results revealed that the expression of miR-142-5p was significantly reduced in AMEC, and was negatively correlated with the expression of CDK5 (r=-0.5451). We also found that miR-142-5p can inhibit CDK5 expression by directly target 3' untranslated region (UTR) of CDK5. Additionally, our findings indicated that the increased expression of CDK5 induces the secretion of inflammatory cytokines. In order to further confirm the involvement of miR-142-5p in the regulation of the inflammatory response in AMEC through its inhibitory effect on CDK5 expression, we studied the inflammatory response in HaCaT cells transfected with small interfering RNA against CDK5 (si-CDK5) and a miR-142-5p inhibitor. The results confirmed that miR-142-5p regulates the inflammatory response in AMEC by downregulating CDK5. In summary, miR-142-5p directly inhibits the CDK5-mediated upregulation of inflammatory cytokines in AMEC, which makes it a potential therapeutic target in this disease.
微小RNA（miRNA）在细胞增殖、分化、凋亡及炎症反应的调控中发挥着重要作用。miR-142-5p是一种重要的炎症相关miRNA，其异常表达与多种炎症相关疾病有关。然而，miR-142-5p在获得性中耳胆脂瘤（AMEC）中的作用及靶向的信号通路尚未完全阐明。细胞周期蛋白依赖性激酶5（CDK5）是CDK家族的一个特殊成员，与经典细胞周期蛋白相比，它在炎症反应中起关键作用。在本研究中，我们调查了miR-142-5p和CDK5在AMEC炎症反应中的作用。我们的结果显示，AMEC中miR-142-5p的表达显著降低，且与CDK5的表达呈负相关（r = -0.5451）。我们还发现，miR-142-5p可通过直接靶向CDK5的3'非翻译区（UTR）来抑制CDK5的表达。此外，我们的研究结果表明，CDK5表达的增加会诱导炎性细胞因子的分泌。为了进一步证实miR-142-5p通过抑制CDK5表达参与AMEC炎症反应的调控，我们研究了用针对CDK5的小干扰RNA（si-CDK5）和miR-142-5p抑制剂转染的HaCaT细胞中的炎症反应。结果证实，miR-142-5p通过下调CDK5来调节AMEC中的炎症反应。总之，miR-142-5p直接抑制AMEC中CDK5介导的炎性细胞因子上调，这使其成为该疾病的潜在治疗靶点。
