miR-205: A Potential Biomedicine for Cancer Therapy

Abstract

microRNAs (miRNAs) are a class of small non-coding RNAs that regulate the expression of their target mRNAs post transcriptionally. miRNAs are known to regulate not just a gene but the whole gene network (signaling pathways). Accumulating evidence(s) suggests that miRNAs can work either as oncogenes or tumor suppressors, but some miRNAs have a dual nature since they can act as both. miRNA 205 (miR-205) is one such highly conserved miRNA that can act as both, oncomiRNA and tumor suppressor. However, most reports confirm its emerging role as a tumor suppressor in many cancers. This review focuses on the downregulated expression of miR-205 and discusses its dysregulation in breast, prostate, skin, liver, gliomas, pancreatic, colorectal and renal cancers. This review also confers its role in tumor initiation, progression, cell proliferation, epithelial to mesenchymal transition, and tumor metastasis. Restoration of miR-205 makes cells more sensitive to drug treatments and mitigates drug resistance. Additionally, the importance of miR-205 in chemosensitization and its utilization as potential biomedicine and nanotherapy is described. Together, this review research article sheds a light on its application as a diagnostic and therapeutic marker, and as a biomedicine in cancer.

Keywords: Targeted Delivery; cancer; miR-205; miRNAs; nanoformulation; tumor suppressor.

Figure 1

(A) Number of peer reviewed articles. Extracted from PubMed, and searched as miR-205, miR-205 in cancer. (B) Pie Chart showing distribution of miR-205 articles with different search criteria. Articles were searched for miR-205 as tumor suppressor in cancer, miR-205 as oncogene in cancer and miR-205 in different cancers.

Figure 2

Role of miR-205 in EMT. Loss of miR-205 is a common phenomenon during the Epithelial to Mesenchymal Transition (EMT). Reversal of EMT is possible once miR-205 is restored in these cells via supplementing it through nanotechnology.

Figure 3

(A) Protein Interaction Network: Network generated by Cytoscape and GeneMANIA was used for the analysis of interaction network. Parameters that were used for networking: Max resultant genes were 20 and max resultant attributes were 10 and the weighing method was automatically selected from weighting methods. (B) Pathway enrichment analysis of key and neighboring proteins. Pathway enrichment analysis and Pie chart of 12 key and 20 neighboring proteins were generated by using ClueGO, a plug-in of Cytoscape (pV ≤ 0.05, with two-sided hypergeometric test and the pV correction is Bonferroni step down).

Figure 4

(A) Preparation of miR-205 loaded MNP nanoformulation. (B) Hemolysis images of miR-205 MNP nanoformulation. Microscopic images showing hemolytic characteristic of human red blood cells. This figure was adopted from our previous publication [215].

Figure 5

Schematic diagram showing restoration of miR-205 through nanoparticles. Delivery of miR-205 with nanoformulations can lead to an enhanced tumor suppressive role of miR-205 in cancer via targeting several signaling pathways/genes.