Potential Targets and Clinical Value of MiR-224-5p in Cancers of the Digestive Tract

Abstract

Background/Aims: MicroRNAs participate in various biological processes in malignant tumors. However, the mechanisms of miR-224-5p in digestive system cancers are not fully understood. A comprehensive investigation of the clinical value and potential targets of miR-224-5p in cancers of the digestive tract is necessary. Methods: Expression profiling data and related-prognostic data of miR-224-5p were acquired from Gene Expression Omnibus, The Cancer Genome Atlas, ArrayExpress, and published literature. The potential target mRNAs of miR-224-5p were predicted using bioinformatics methods and finally annotated using Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results: MiR-224-5p is up-regulated in digestive system cancers (SMD=0.69, 95% CI: 0.43-0.96, P<0.0001) and exhibits a moderate diagnostic ability (AUC=0.84, 95% CI: 0.80-0.87). Our data also demonstrated that miR-224-5p is statistically significantly correlated with overall survival univariate analysis (HR=1.69, 95% CI: 1.15-2.49, P=0.007) and multivariate analysis (HR=2.39, 95% CI: 1.74-3.30, P<0.0001). In total, 388 potential miR-224-5p target mRNAs were predicted by bioinformatics methods. GO annotation analysis revealed that the top terms of miR-224-5p in biological process, cellular component and molecular function were system development, neuron part, and transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding, respectively. Moreover, eight pathways were identified in KEGG pathway enrichment analysis. Conclusions: MiR-224-5p is up-regulated and has the potential to become a diagnostic and prognostic biomarker in digestive system cancers. MiR-224-5p might play vital roles in cancers of the digestive tract but the exact molecular mechanisms need further study and verification.

LncRNA SNHG4 promotes tumour growth by sponging miR‐224‐3p and predicts poor survival and recurrence in human osteosarcoma

“…It is reported that miR‐224 acts a dual role in cancer. On the one hand, increased expression of miR‐224‐5p harbours the potential to be a diagnostic and prognostic biomarker in digestive system cancers, and is associated with the cisplatin resistance in ovarian carcinoma . On the other hand, miR‐224‐3p represses autophagy in cervical cancer by targeting FIP200 and is downregulated in multidrug‐resistant breast cancer cells .…”

Downregulation of miR‑224‑5p in prostate cancer and its relevant molecular mechanism via TCGA, GEO database and in�silico analyses

“…Previous studies have demonstrated that the abnormal expression of miR-224-5p was a crucial factor in the initiation and progress of tumors. For example, the high expression of miR-224-5p was likely to be involved in the onset of digestive tract malignancy ( 38 ); the expression of miR-224-5p was significantly reduced in mucinous breast cancer ( 39 ); and cell experiments and histologic examination performed by Zheng et al revealed that miR-224-5p exhibited lower expression in uveal melanoma ( 40 ). However, studies on the expression of miR-224-5p in PCa have been limited.…”

Circulating miRNAs in Small Extracellular Vesicles Secreted by a Human Melanoma Xenograft in Mouse Brains

“…Interestingly, most of the target genes discussed above are targeted by the human-specific miR-224-5p, with the exception of TP63, targeted by miR-1246, and STK4, targeted by miR-373-3p. miR-224-5p was initially classified as a tumor suppressor [87], but it is emerging that miR-224-5p could also display oncogenic functions [88][89][90]. Very interestingly, we found that this miRNA is more expressed in the EVs from metastatic melanoma patients compared to primary cases and is absent in the EVs from healthy controls, thus being a potentially interesting biomarker of melanoma progression.…”