Pathway analysis of cancer-associated microRNA targets.
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.
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.
Hao
H
Yang
Haiyang
H
Zhang
Lin
L
Zhu
Jin
J
Wang
Chenyu
C
Zhang
Donghai
D
Li
D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D058977:Molecular Sequence Annotation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction
D035683:MicroRNAs