Kaushik Pankhuri, Kumar Arun
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India.
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India.
Pathol Res Pract. 2022 Jan;229:153741. doi: 10.1016/j.prp.2021.153741. Epub 2021 Dec 18.
Ever since their discovery, microRNAs (miRNAs/miRs) have astonished us by the plethora of processes they regulate, and thus adding another dimension to the gene regulation. They have been implicated in several diseases affecting cardiovascular, neurodegenerative, hepatic, autoimmune and inflammatory functions. A primate specific exonic miRNA, miR-198 has been vastly studied during the past decade, and shown to have a critical role in wound healing. The aberrant expression of miR-198 was first reported in schizophrenia, linking it to neural development. Later, its dysregulation and tumor suppressive role was reported in hepatocellular carcinoma. However, this was just a beginning, and after which there was an explosion of reports linking miR-198 deregulation to cancers and other ailments. The first target to be identified for miR-198 was Cyclin T1 in monocytes affecting HIV1 replication. Depending on the type of cancer, miR-198 has been shown to function either as a tumor suppressor or an oncomir. Interestingly, miR-198 is not only known to regulate multiple targets and pathways, but also is itself regulated by several circular RNAs and long-non-coding RNAs, highlighting a complex regulatory network. This review highlights the currently understood mechanism and regulation of miR-198 in different diseases, and its possible diagnostic and therapeutic potential.
自发现以来,微小RNA(miRNA/miR)就因其调控的众多过程而令我们惊讶不已,从而为基因调控增添了另一个维度。它们与多种影响心血管、神经退行性、肝脏、自身免疫和炎症功能的疾病有关。灵长类动物特有的外显子miRNA miR-198在过去十年中得到了广泛研究,并被证明在伤口愈合中起关键作用。miR-198的异常表达最早在精神分裂症中被报道,将其与神经发育联系起来。后来,其失调和肿瘤抑制作用在肝细胞癌中被报道。然而,这仅仅是个开始,此后大量报道将miR-198失调与癌症和其他疾病联系起来。miR-198第一个被确定的靶点是单核细胞中的细胞周期蛋白T1,它影响HIV1复制。根据癌症类型,miR-198已被证明既可以作为肿瘤抑制因子发挥作用,也可以作为致癌miRNA发挥作用。有趣的是,miR-198不仅已知能调控多个靶点和途径,而且其本身也受几种环状RNA和长链非编码RNA的调控,这突出了一个复杂的调控网络。本综述重点介绍了目前对miR-198在不同疾病中的作用机制和调控的理解,以及其可能的诊断和治疗潜力。