miR-451a,也称为MicroRNA-451a,是一种小的非编码RNA,属于MicroRNA家族。MicroRNA是一类长度约22个核苷酸的非编码RNA分子,它们通过与目标mRNA的3'非翻译区(3'UTR)结合,调节基因表达。miR-451a通过抑制目标基因的翻译或促进其降解来发挥其功能,从而影响细胞生长、分化、凋亡和代谢等多种生物学过程。
miR-451a在多种疾病中发挥着重要作用,包括癌症、炎症和代谢性疾病。在癌症中,miR-451a可以作为肿瘤抑制因子或致癌因子。例如,miR-451a在胆管癌中下调,并通过抑制巨噬细胞迁移抑制因子(MIF)介导的PI3K/AKT信号通路,抑制肿瘤的进展[2]。而在头颈部鳞状细胞癌(HNSCC)中,miR-451a在细胞核中富集,并通过激活KDM7A转录,导致西妥昔单抗耐药性[3]。
在炎症方面,miR-451a通过抑制炎症反应,在骨愈合中发挥免疫调节作用。例如,脂肪来源干细胞(ADSC)衍生的外泌体(ADSC-Exos)富含miR-451a,并通过调节巨噬细胞M1/M2表型极化,促进骨组织修复[1]。此外,miR-451a还可以通过靶向IL-6受体(IL-6R)和14-3-3ζ,调节血红蛋白诱导的炎症,从而对溶血性疾病(如疟疾和镰状细胞病)发挥保护作用[4]。
miR-451a还在其他疾病中发挥作用。例如,在心脏疾病中,miR-451a可以保护心肌细胞免受缺氧/再氧合损伤[5]。此外,miR-451a在耳部疾病和听力丧失中也发挥着重要作用,例如,miR-451a在噪声暴露后的血浆水平升高,并与听力丧失相关[6]。
综上所述,miR-451a是一种重要的MicroRNA,参与调节多种生物学过程,包括癌症、炎症和代谢性疾病。miR-451a的功能取决于其目标基因和细胞类型。miR-451a的研究有助于深入理解MicroRNA的生物学功能和疾病发生机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Li, Rui, Li, Dize, Wang, Huanan, Xu, Jie, Ji, Ping. 2022. Exosomes from adipose-derived stem cells regulate M1/M2 macrophage phenotypic polarization to promote bone healing via miR-451a/MIF. In Stem cell research & therapy, 13, 149. doi:10.1186/s13287-022-02823-1. https://pubmed.ncbi.nlm.nih.gov/35395782/
2. Obata, Taisuke, Tsutsumi, Koichiro, Ueta, Eijiro, Okada, Hiroyuki, Otsuka, Motoyuki. 2023. MicroRNA-451a inhibits gemcitabine-refractory biliary tract cancer progression by suppressing the MIF-mediated PI3K/AKT pathway. In Molecular therapy. Nucleic acids, 34, 102054. doi:10.1016/j.omtn.2023.102054. https://pubmed.ncbi.nlm.nih.gov/38111913/
3. Zhai, Peisong, Tong, Tong, Wang, Xiaoning, Zhang, Jianjun, Guo, Haiyan. 2024. Nuclear miR-451a activates KDM7A and leads to cetuximab resistance in head and neck squamous cell carcinoma. In Cellular and molecular life sciences : CMLS, 81, 282. doi:10.1007/s00018-024-05324-x. https://pubmed.ncbi.nlm.nih.gov/38943031/
4. Bashi, Alaijah, Lekpor, Cecilia, Hood, Joshua L, Stiles, Jonathan K, Driss, Adel. 2023. Modulation of Heme-Induced Inflammation Using MicroRNA-Loaded Liposomes: Implications for Hemolytic Disorders Such as Malaria and Sickle Cell Disease. In International journal of molecular sciences, 24, . doi:10.3390/ijms242316934. https://pubmed.ncbi.nlm.nih.gov/38069257/
5. Czosseck, Andreas, Chen, Max M, Hsu, Chuan-Chih, Livkisa, Dora, Lundy, David J. 2024. Extracellular vesicles from human cardiac stromal cells up-regulate cardiomyocyte protective responses to hypoxia. In Stem cell research & therapy, 15, 363. doi:10.1186/s13287-024-03983-y. https://pubmed.ncbi.nlm.nih.gov/39396003/
6. Mahmoudian-Sani, Mohammad-Reza, Mehri-Ghahfarrokhi, Ameneh, Ahmadinejad, Fereshteh, Saidijam, Massoud, Jami, Mohammad-Saeid. 2017. MicroRNAs: effective elements in ear-related diseases and hearing loss. In European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery, 274, 2373-2380. doi:10.1007/s00405-017-4470-6. https://pubmed.ncbi.nlm.nih.gov/28224282/