Xu Guangmeng, Yang Zecheng, Sun Yamin, Dong Hongmei, Ma Jingru
Department of Colorectal Surgery, The Second Hospital of Jilin University, Changchun, 130000, China.
Department of Gastrointestinal Surgery, The Second Hospital of Jilin University, Changchun, 130000, China.
Discov Oncol. 2021 Sep 20;12(1):33. doi: 10.1007/s12672-021-00430-9.
Sphingosine-1-phosphate (S1P), a pleiotropic lipid mediator, participates in various cellular processes during tumorigenesis, including cell proliferation, survival, drug resistance, metastasis, and angiogenesis. S1P is formed by two sphingosine kinases (SphKs), SphK1 and SphK2. The intracellularly produced S1P is delivered to the extracellular space by ATP-binding cassette (ABC) transporters and spinster homolog 2 (SPNS2), where it binds to five transmembrane G protein-coupled receptors to mediate its oncogenic functions (S1PR1-S1PR5). MicroRNAs (miRNAs) are small non-coding RNAs, 21-25 nucleotides in length, that play numerous crucial roles in cancer, such as tumor initiation, progression, apoptosis, metastasis, and angiogenesis via binding to the 3'-untranslated region (3'-UTR) of the target mRNA. There is growing evidence that various miRNAs modulate tumorigenesis by regulating the expression of SphKs, and S1P receptors. We have reviewed various roles of miRNAs, SphKs, S1P, and S1P receptors (S1PRs) in malignancies and how notable miRNAs like miR-101, miR-125b, miR-128, and miR-506, miR-1246, miR-21, miR-126, miR499a, miR20a-5p, miR-140-5p, miR-224, miR-137, miR-183-5p, miR-194, miR181b, miR136, and miR-675-3p, modulate S1P signaling. These tumorigenesis modulating miRNAs are involved in different cancers including breast, gastric, hepatocellular carcinoma, prostate, colorectal, cervical, ovarian, and lung cancer via cell proliferation, invasion, angiogenesis, apoptosis, metastasis, immune evasion, chemoresistance, and chemosensitivity. Therefore, understanding the interaction of SphKs, S1P, and S1P receptors with miRNAs in human malignancies will lead to better insights for miRNA-based cancer therapy.
鞘氨醇-1-磷酸（S1P）是一种多效性脂质介质，在肿瘤发生过程中参与多种细胞过程，包括细胞增殖、存活、耐药性、转移和血管生成。S1P由两种鞘氨醇激酶（SphKs），即SphK1和SphK2形成。细胞内产生的S1P通过ATP结合盒（ABC）转运蛋白和spinster同源物2（SPNS2）被输送到细胞外空间，在那里它与五种跨膜G蛋白偶联受体结合以介导其致癌功能（S1PR1-S1PR5）。微小RNA（miRNA）是长度为21-25个核苷酸的小型非编码RNA，通过与靶mRNA的3'-非翻译区（3'-UTR）结合，在癌症中发挥许多关键作用，如肿瘤起始、进展、凋亡、转移和血管生成。越来越多的证据表明，各种miRNA通过调节SphKs和S1P受体的表达来调节肿瘤发生。我们综述了miRNA、SphKs、S1P和S1P受体（S1PRs）在恶性肿瘤中的各种作用，以及像miR-101、miR-125b、miR-128和miR-506、miR-1246、miR-21、miR-126、miR499a、miR20a-5p、miR-140-5p、miR-224、miR-137、miR-183-5p、miR-194、miR181b、miR136和miR-675-3p等显著的miRNA如何调节S1P信号传导。这些调节肿瘤发生的miRNA通过细胞增殖、侵袭、血管生成、凋亡、转移、免疫逃逸、化疗耐药性和化疗敏感性参与包括乳腺癌、胃癌、肝细胞癌、前列腺癌、结直肠癌、宫颈癌、卵巢癌和肺癌在内的不同癌症。因此，了解SphKs、S1P和S1P受体与miRNA在人类恶性肿瘤中的相互作用将为基于miRNA的癌症治疗带来更好的见解。
