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.
Highlights
MicroRNAs are a class of noncoding small RNAs that negatively regulate the translation and stability of mRNAs
We performed a comprehensive investigation on transcriptional associations between miRNAs and their host genes across 21 cancer types using The Cancer Genome Atlas (TCGA) datasets
We detected 79 consistently and strongly coexpressed miRNA-host pairs across all cancer types, where host genes can be used as a proxy for the expression profiles of the embedded miRNAs
Summary
MicroRNAs (miRNAs) are a class of noncoding small RNAs that negatively regulate the translation and stability of mRNAs. Previous studies have reported contradictory results on co-transcriptional patterns between miRNAs and their host genes. Biomedicines 2021, 9, 1263 interplay between intragenic miRNAs and host genes makes co-transcription patterns even more complicated [9]. Intronic miRNAs play a synergistic or antagonistic role as a partner or enemy to their host genes by targeting the same biological pathways or even the same genes/proteins, which would enhance or decouple the coregulation [13,14,15]. Studies on the transcriptional association of miRNAs and host genes, are very limited in cancer. The Cancer Genome Atlas (TCGA) program has generated multi-omics measurements across thousands of tumors, which provides an unprecedented opportunity to study cancer common and specific co-transcriptional patterns between miRNAs and host genes. Dissecting the relationship between miRNAs and host genes in cancer can provide important information for cancer therapy [28,29], can help avoid the unintentional miRNA ablation [30], and assist in miRNA target prediction [31]
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