Abstract
PurposeThe prognostic role of miR-204-5p (previous ID: miR-204) is varied and inconclusive in diverse types of malignant neoplasm. Therefore, the purposes of the study comprehensively explore the overall prognostic role of miR-204-5p based on high-throughput microRNA sequencing data, and to investigate the potential role of miR-204-5p via bioinformatics approaches.Materials and MethodsThe data of microRNA sequencing and survival were downloaded from The Cancer Genome Atlas (TCGA), and the prognostic value of miR-204-5p was analyzed by using Kaplan-Meier and univariate cox regressions. Then a meta-analysis was conducted with all TCGA data and relevant studies collected from literature. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. The prospective molecular mechanism of miR-204-5p was also assessed at a functional level with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-to-protein interactions (PPI) network.ResultsFrom TCGA data, the prognostic value of miR-204-5p obviously varied among 20 types of cancers. The pooled HR was 0.928 (95% CI: 0.774–1.113, P = 0.386, 6203 cases of malignancies). For the meta-analysis based on 15 studies from literature, the pooled HR was 0.420 (95% CI: 0.306–0.576, P < 0.001, 1783 cases of malignancies) for overall survival (OS). Furthermore, the combined HR from both TCGA and literature was 0.708 (95% CI: 0.600–0.834, P < 0.001, 7986 cases of malignancies). Subgroup analyses revealed that miR-204-5p could act as a prognostic marker in cancers of respiratory system and digestive system. Functional analysis was conducted on genes predicted as targets (n = 2057) after the overlay genes from six out of twelve software were extracted. Two significant KEGG pathways were enriched (hsa04360: Axon guidance and hsa04722: Neurotrophin signaling pathway). PPI network revealed some hub genes/proteins (CDC42, SOS1, PIK3R1, MAPK1, PLCG1, ESR1, MAPK11, and AR).ConclusionsThe current study demonstrates that over-expression of miR-204-5p could be a protective factor for a certain group of cancers. Clinically, the low miR-204-5p level could gain a predictive value for a poor survival in cancers of respiratory system and digestive system. The detailed molecular mechanisms of miR-204-5p remain to be verified.
Highlights
MicroRNAs are a class of noncoding RNAs with about 18–25 nucleotides
For the meta-analysis based on 15 studies from literature, the pooled hazard ratios (HRs) was 0.420 for overall survival (OS)
The combined HR from both The Cancer Genome Atlas (TCGA) and literature was 0.708
Summary
One of the mechanisms through which miRNAs regulate gene expression involves the base-pairing primarily with the 3′-untranslated regions (3′-UTRs), and more rarely with 5′end of their target mRNAs through the “seed” sequences of the miRNAs [1]. MiRNAs can function as a switch and a finetuner of the gene regulatory network, which may consist of hundreds, even thousands of potential target genes [2]. Increasing evidence has shown that imbalance of miRNA expression can lead to a wide variety of diseases, including inheriting diseases, obesity, cardiovascular diseases, anxiety disorder and cancers. Previous scientific evidence indicates that aberrant miRNAs expression exists in numerous cancers, and miRNAs participate in tumorigenesis and progression, functioning as oncogenes or tumor suppressors [3, 4]. The abnormal expression of miRNAs is apparently related to deviant cancerous outcomes, suggesting that miRNAs are potential substantial biomarkers of cancers [5,6,7,8,9,10,11,12,13]
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