Table 1.

Advantages and disadvantages of current miRNA inhibitors and enhancer

Methods	Type	Description	Examples	Target/function	Advantages	Limitations
miRNA mimics	Enhancer	miRNA mimic is chemically synthesized ds miRNA like RNA, designed to perform similar functions as endogenous miRNA	Let-7 mimic MRX34 (a miRNA-34a mimic)	Delivery of let-7 mimic decreased the prevalence of K-ras-dependent lung cancers [57] miRNA-34a mimics reduced tumor growth in liver cancer [58]	Predicted to target the same sets of genes because they share the same sequence as natural miRNA [59]	Have immune related adverse effects [60] Causes non-specific changes of gene expression due to higher concentration delivery of mimics inside the cells [61] Often chemically modified for stability which might have different effects than endogenous miRNA [61] Might have negative effects because miRNA mimic complimentary strand acts inappropriately [62]
AntagomiRs	Inhibitor	AntagomiR is chemically synthesized single-stranded RNA and specially developed for inhibiting the function of endogenous miRNA	miR-10b antagomir	miR-10b antagomir reduced target protein, homeobox D10, and lung metastasis of breast cancer [63]	Chemical modification gives them higher affinity to cell membrane and higher stability [64]	Found to cause lowering of white blood cells, increase serum levels of bilirubin, ALT and AST [63]
miRNA sponges	Inhibitor	Contains complementary binding sites for target miRNA but produced within the cell by transgene	CDR1as/ciRS-7-lncRNA ZFAS1	Targets miRNA-7 mediated insulin secretion by islet cells [65] Regulates miR-190a-3p to control the development of cervical cancer [66]	Easy to deliver into difficult-to-transfect cell lines or cells in vivo by viral vector [67] Sponges interact with the mature miRNA, thus clustering of miRNA precursors does not affect their effectiveness [67]	Binds in the seeding region of the miRNA, thus might inhibit many genes by targeting many miRNAs of the same family [67]
LNA-modified antisense oligonucleotides	Inhibitor	RNA analogs in which a methylene connection between the 2′-oxygen and the 4′-carbon “locks” the ribose ring	miR-92a-3p	Inhibits miR-92a-3p induced colon cancer cells proliferation [68] Regulates EMT to prevent miR-205-5p-mediated breast cancer metastasis [69]	Chemical modification gives them more affinity to the target and stability towards endogenous nucleases activity [70]	They would increase nuclease resistance and prevent the targeted probe from degradation; they cannot be inserted at the 5′ terminus of the probe or at the nearby nucleotide [71]

MRX34 liposomal formulation of miR-34a, ALT alanine transaminase, AST aspartate aminotransferase, CDR1 cerebellar degeneration-related protein 1, LNA locked nucleic acid, EMT epithelial-mesenchymal transition