El Founini Younes, Chaoui Imane, Dehbi Hind, El Mzibri Mohammed, Abounader Roger, Guessous Fadila
Unit of Biology and Medical Research, National Center of Energy, Sciences and Nuclear Techniques, Rabat, Morocco.
Cellular and Molecular Pathology Laboratory, Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco.
Microrna. 2021;10(2):109-122. doi: 10.2174/2211536610666210527102522.
Noncoding RNAs have emerged as key regulators of the genome upon gene expression profiling and genome-wide sequencing. Among these noncoding RNAs, microRNAs are short noncoding RNAs that regulate a plethora of functions, biological processes and human diseases by targeting the messenger RNA stability through 3'UTR binding, leading to either mRNA cleavage or translation repression, depending on microRNA-mRNA complementarity degree. Additionally, strong evidence has suggested that dysregulation of miRNAs contributes to the etiology and progression of human cancers, such as lung cancer, the most common and deadliest cancer worldwide. Indeed, by acting as oncogenes or tumor suppressors, microRNAs control all aspects of lung cancer malignancy, including cell proliferation, survival, migration, invasion, angiogenesis, cancer stem cells, immune-surveillance escape, and therapy resistance; and their expressions are often associated with clinical parameters. Moreover, several deregulated microRNAs in lung cancer are carried by exosomes and microvesicles and secreted in body fluids, mainly the circulation, where they conserve their stable forms. Subsequently, seminal efforts have been focused on extracellular microRNAs levels as noninvasive diagnostic and prognostic biomarkers in lung cancer. In this review, focusing on recent literature, we summarize the deregulation, mechanisms of action, functions and highlight clinical applications of miRNAs for better management and design of future lung cancer targeted therapies.
在基因表达谱分析和全基因组测序后,非编码RNA已成为基因组的关键调节因子。在这些非编码RNA中,微小RNA是短的非编码RNA,通过与信使RNA的3'非翻译区(3'UTR)结合来靶向信使RNA的稳定性,从而调节大量功能、生物过程和人类疾病,根据微小RNA与信使RNA的互补程度,导致信使RNA的切割或翻译抑制。此外,有力证据表明,微小RNA的失调与人类癌症的病因和进展有关,如肺癌,它是全球最常见、最致命的癌症。事实上,通过充当癌基因或肿瘤抑制因子,微小RNA控制肺癌恶性肿瘤的各个方面,包括细胞增殖、存活、迁移、侵袭、血管生成、癌症干细胞、免疫监视逃逸和治疗抗性;并且它们的表达通常与临床参数相关。此外,肺癌中几种失调的微小RNA由外泌体和微泡携带并分泌到体液中,主要是循环系统,在那里它们保持稳定的形式。随后,开创性的工作集中在将细胞外微小RNA水平作为肺癌的非侵入性诊断和预后生物标志物。在这篇综述中,我们聚焦于近期文献,总结了微小RNA的失调、作用机制、功能,并着重介绍了其在肺癌更好管理和未来靶向治疗设计中的临床应用。