Versatile role of miR-24/24-1*/24-2* expression in cancer and other human diseases

Abstract

MiRNAs (miRs) have been proven to be well-validated therapeutic targets. Emerging evidence has demonstrated that intricate, intrinsic and paradoxical functions of miRs are context-dependent because of their multiple upstream regulators, broad spectrum of downstream molecular targets and distinct expression in various tissues, organs and disease states. Targeted therapy has become an emerging field of research. One key for the development of successful miR-based/targeted therapy is to acquire integrated knowledge of its regulatory network and its association with disease phenotypes to identify critical nodes of the underlying pathogenesis. Herein, we systematically summarized the comprehensive role of miR-24-3p (miR-24), along with its passenger strands miR-24-1-5p* (miR-24-1) and miR-24-2-5p* (miR-24-2), emphasizing their microenvironment, intracellular targets, and associated gene networks and regulatory phenotypes in 18 different cancer types and 13 types of other disorders. MiR-24 targets and regulates numerous genes in various cancer types and enhances the expression of several oncogenes (e.g., cMyc, BCL2 and HIF1), which are challenging in terms of druggability. In contrast, several tumor suppressor proteins (p21 and p53) have been reported to be downregulated by miR-24. MiR-24 also regulates the cell cycle and is associated with numerous cancer hallmarks such as apoptosis, proliferation, metastasis, invasion, angiogenesis, autophagy, drug resistance and other diseases pathogenesis. Overall, miR-24 plays an emerging role in the diagnosis, prognosis and pathobiology of various diseases. MiR-24 is a potential target for targeted therapy in the era of precision medicine, which expands the landscape of targetable macromolecules, including undruggable proteins.

Keywords: MiR-24/24-1*/24-2*; regulatory role in cancer and other diseases; target genes and regulatory networks; therapeutic target.

Figure 1

Schematic representation of the miR biogenesis.

Figure 2

Alignment of two different precursors (has-miR-24-1 and has-miR-24-2) of miR-24 located (denoted by orange line) in two distant chromosomal regions (9q22.32 and 19p13.12) in human genome. Both the precursors after processed by RNase-III-type enzymes (Drosha and Dicer) formed identical mature products has-miR-24-3p (miR-24). Sequences and predicted hairpin loop structures of both hsa-miR-24-1 (pri-miR-24-1) and hsa-miR-24-2 (pri-miR-24-2) also represented into the figure. Sequences represented in blue corresponding to guide strand miR-24-3p (miR-24) sequence. Sequences of the sister or passenger or star (*) strand formed (miR-24-1 and miR-24-2) after maturation of both the precursors are represented in green. Red arrows represented the Drosha cleavage site.

Figure 3

Schematic representation of target genes, regulatory pathways and interactive function of miR-24 in different cancer types. Black thick arrow directed from each cancer type indicates the regulatory genes. Gray thick arrow indicates the regulatory cancer phenotypes. Black thin arrow pointed upward and downward indicate the upregulation and downregulation of the corresponding gene’s expression, respectively. Yellow arrow pointed upward and downward indicate the upregulation and downregulation of the corresponding phenotypes, respectively.

Figure 4

Schematic representation of target genes, regulatory pathways and interactive functions of miR-24-1 and miR-24-2 in various cancers and other diseases. Black thick arrow directed the regulatory genes. Gray thick arrow indicates the regulatory phenotypes and biological functions. Black thin arrow pointed upward and downward indicate the upregulation and downregulation of the corresponding gene’s expression, respectively. Yellow arrow pointed upward and downward indicate the upregulation and downregulation of the corresponding phenotypes, respectively.

Figure 5

Schematic representation of target genes, regulatory pathways and interactive functions of miR-24 in different diseases. Black thick arrow directed the regulatory genes. Gray thick arrow indicates the regulatory phenotypes and biological functions. Black thin arrow pointed upward and downward indicate the upregulation and downregulation of the corresponding gene’s expression, respectively. Yellow arrow pointed upward and downward indicate the upregulation and downregulation of the corresponding biological functions, respectively.