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Pan-Cancer Analysis Reveals Common and Specific Relationships between Intragenic miRNAs and Their Host Genes
Baohong Liu1, Yu Shyr2,3, Qi Liu2,3
1Key Laboratory of Veterinary Parasitology of Gansu Province, State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.
Abstract:
MicroRNAs (miRNAs) are small endogenous non-coding RNAs that play important roles in regulating gene expression. Most miRNAs are located within or close to genes (host). miRNAs and their host genes have either coordinated or independent transcription. We performed a comprehensive investigation on co-transcriptional patterns of miRNAs and host genes based on 4707 patients across 21 cancer types. We found that only 11.6% of miRNA-host pairs were co-transcribed consistently and strongly across cancer types. Most miRNA-host pairs showed a strong coexpression only in some specific cancer types, demonstrating a high heterogenous pattern. For two particular types of intergenic miRNAs, readthrough and divergent miRNAs, readthrough miRNAs showed higher coexpression with their host genes than divergent ones. miRNAs located within non-coding genes had tighter co-transcription with their hosts than those located within protein-coding genes, especially exonic and junction miRNAs. A few precursor miRNAs changed their dominate form between 5' and 3' strands in different cancer types, including miR-486, miR-99b, let-7e, miR-125a, let-7g, miR-339, miR-26a, miR-16, and miR-218, whereas only two miRNAs with multiple host genes switched their co-transcriptional partner in different cancer types (miR-219a-1 with SLC39A7/HSD17B8 and miR-3615 with RAB37/SLC9A3R1). miRNAs generated from distinct precursors (such as miR-125b from miR-125b-1 or miR-125b-2) were more likely to have cancer-dependent main contributors. miRNAs and hosts were less co-expressed in KIRC than other cancer types, possibly due to its frequent VHL mutations. Our findings shed new light on miRNA biogenesis and cancer diagnosis and treatments.
Insights
Most microRNA-host gene pairs show inconsistent co-transcription across 21 cancer types, revealing significant heterogeneity. This study highlights cancer-specific expression patterns and implications for miRNA biogenesis and cancer treatment.
Area of Science:
- Genomics
- Molecular Biology
- Cancer Research
Background:
- MicroRNAs (miRNAs) are small non-coding RNAs crucial for gene expression regulation.
- miRNAs are often transcribed alongside their host genes, influencing their expression patterns.
- Understanding miRNA-host gene co-transcription is vital for deciphering gene regulation in various biological contexts, including cancer.
Purpose of the Study:
- To comprehensively investigate the co-transcriptional patterns between miRNAs and their host genes across diverse cancer types.
- To identify consistent and cancer-specific co-expression relationships between miRNAs and host genes.
- To explore factors influencing miRNA-host gene co-transcription, such as miRNA location and gene type.
Main Methods:
- Analysis of miRNA and host gene expression data from 4707 patients across 21 cancer types.
- Assessment of co-transcriptional patterns, including consistency, strength, and heterogeneity.
- Categorization of miRNAs based on their genomic location (intergenic, intronic) and host gene type (coding, non-coding).
Main Results:
- Only 11.6% of miRNA-host pairs exhibited consistent and strong co-transcription across all cancer types.
- Most miRNA-host pairs displayed cancer-specific co-expression, indicating significant heterogeneity.
- Readthrough intergenic miRNAs showed higher coexpression with hosts than divergent miRNAs; miRNAs in non-coding genes had tighter co-transcription than those in protein-coding genes.
- Specific miRNAs demonstrated strand switching or switched host genes in different cancer types, with notable differences observed in KIRC.
Conclusions:
- MiRNA-host gene co-transcription is highly heterogeneous and largely cancer-dependent.
- The genomic location and type of host gene significantly influence miRNA co-transcription.
- Findings provide insights into miRNA biogenesis, regulation, and potential utility in cancer diagnosis and therapy.
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