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An In Vitro Protocol for Evaluating MicroRNA Levels, Functions, and Associated Target Genes in Tumor Cells
Published on: May 21, 2019
Pathway analysis of cancer-associated microRNA targets
Hao Yang1, Haiyang Zhang, Lin Zhu
1Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, PR China.
Abstract:
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.
Insights
Cancer-associated microRNAs (CA-miRNAs) regulate key cancer processes post-transcriptionally. This study reveals how CA-miRNAs influence transcription factors and protein kinases, impacting cell signaling pathways crucial for carcinogenesis.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Carcinogenesis involves genetic and epigenetic alterations, with microRNAs (miRNAs) regulating gene expression post-transcriptionally.
- The specific pathways and functions of cancer-associated miRNAs (CA-miRNAs) in carcinogenesis remain incompletely understood.
Purpose of the Study:
- To investigate the role of eleven previously identified CA-miRNAs in cancer-related pathways.
- To analyze the function and pathway relevance of CA-miRNA-targeted genes in the context of carcinogenesis.
Main Methods:
- Function and pathway analysis of genes targeted by eleven selected CA-miRNAs.
- Prediction of CA-miRNA targets and their involvement in canonical cancer pathways.
Main Results:
- CA-miRNAs primarily regulate transcription factors and protein kinases at the post-transcriptional level.
- Target genes are significantly involved in transcriptional regulation, cell differentiation, proliferation, endocytosis, and migration.
- Five canonical pathways were identified as key regulators of core carcinogenesis processes by CA-miRNAs.
Conclusions:
- CA-miRNAs play a significant role in regulating fundamental cancer processes through specific signaling pathways.
- These findings provide a foundation for developing novel therapeutic strategies targeting CA-miRNAs in cancer treatment.
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