Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, PR China.
Int J Oncol. 2012 Dec;41(6):2213-26. doi: 10.3892/ijo.2012.1658. Epub 2012 Oct 11.
Carcinogenesis is a multi-step process, which includes oncogene activation, mutation silencing of tumor suppressor genes, impairment of chromosomes or epigenetic changes such as CpG island methylation through various cellular pathways, involving a series of somatic genetic alterations. Furthermore, miRNAs present a mechanism by which genes with diverse functions on multiple pathways can be simultaneously regulated at the post-transcriptional level. However, little is known about the cancer-related pathways through which cancer-associated miRNAs (CA-miRNAs) regulate these processes representing either positive or negative functions in carcinogenesis. This study investigated eleven miRNAs previously identified as cancer-related regulators. Using function and pathway analysis of their targeted genes, the relevance of miRNA regulation in the induction of cancer can be observed. The results showed that CA-miRNAs may function in the post-transcriptional level mainly through manipulating the expression of transcription factors and protein kinases, and target genes for the CA-miRNAs were most prominently predicted to function in the regulation of transcription. Our analysis also highlighted the potential of these CA-miRNAs to regulate the cell differentiation, proliferation, endocytosis and migration signaling logically required to cause a cancer cell mainly through five canonical pathways. Combined with previous cancer studies, the analysis of the relevance between functions of CA-miRNAs and cancer-related pathways exploring different internal carcinogenesis stimuli also revealed the potential of the top five pathways to regulate core carcinogenesis processes. These findings should form a useful knowledge base for potential future development of novel therapeutic treatments.
癌症发生是一个多步骤的过程，包括癌基因激活、肿瘤抑制基因的突变沉默、染色体损伤或表观遗传改变，如 CpG 岛甲基化，通过各种细胞途径，涉及一系列体细胞遗传改变。此外，miRNA 提供了一种机制，通过该机制，具有多种功能的基因可以在多个途径上同时在转录后水平被调节。然而，关于癌症相关 miRNA（CA-miRNA）通过哪些癌症相关途径来调节这些过程，以及这些过程在癌症发生中是发挥积极作用还是消极作用，目前知之甚少。本研究调查了之前确定为癌症相关调节剂的十一种 miRNA。通过对其靶基因的功能和途径分析，可以观察到 miRNA 调节在癌症诱导中的相关性。结果表明，CA-miRNA 可能主要通过操纵转录因子和蛋白激酶的表达在转录后水平发挥作用，CA-miRNA 的靶基因最显著地预测在转录调控中发挥作用。我们的分析还强调了这些 CA-miRNA 调节细胞分化、增殖、内吞和迁移信号的潜力，这些信号逻辑上需要导致癌细胞主要通过五个经典途径。结合以前的癌症研究，对 CA-miRNA 的功能与癌症相关途径之间的相关性的分析，探索不同的内在致癌刺激，也揭示了前五个途径调节核心致癌过程的潜力。这些发现应该为潜在的新治疗方法的未来发展形成一个有用的知识库。
