Therapeutic potential of targeting mirnas to prostate cancer tumors: using psma as an active target

Figures & data

Figure 1. miRNA biogenesis and mechanisms of action in posttranscriptional gene regulation. miRNA biogenesis begins with miRNA transcription from DNA via the action of RNA polymerase II to generate primary hairpin miRNA (pri-miRNA). Then, pri-miRNA is cleaved by the RNase III drosha and its binding partner DiGeorge syndrome critical region gene 8 (DGCR8), which recognizes the hairpin structures in pri-miRNA and processes them to form precursor miRNA (pre-miRNA). The resulting pre-miRNA is exported to the cytoplasm by Exportin-5, a Ran-GTP-dependent dsRNA-binding protein. In the cytoplasm, another RNase III enzyme, dicer, further processes pre-miRNA, cleaving its hairpin and thus producing a mature miRNA duplex. Then, one strand is loaded into an argonaute (AGO) family member to form the miRNA-induced silencing complex (RISC) that recognizes the mRNA target via sequence complementarity, resulting in mRNA degradation or translation inhibition.

Figure 2. Summary of the important miRnas involved in PC.

Table 1. Challenges to miRNA usage for targeted drug delivery and possible solutions.

Challenges	Possible Solutions
Degradation of miRNAs by nucleases	Changing the surface charge and improving their stability
Filtration in the spleen and kidneys Destruction by macrophages while in the circulatory system	Chemical modification and/or local administration
Penetration through the cell membrane and extracellular matrix	Active targeting via specific ligands and use of cell-penetrating moieties
Poor endosomal release and intracellular localization problems	Use of conjugating peptides, lytic reactions, or miRNA sponges
Ability to target multiple mRNAs	Local administration and active targeting via specific ligands

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.