Development of Novel Therapeutic Agents by Inhibition of Oncogenic MicroRNAs
Abstract
:1. Introduction
2. OncomiRs
3. OncomiR-Targeting Strategies
3.1. Targeting an OncomiRs by Specifically Inhibiting Their Mature Form
3.2. Targeting OncomiR by Small Molecules
3.3. Multiple-OncomiR Targeting by a miRNA Sponge
3.4. Targeting the OncomiR Synthesis Pathway by Genome or RNA Editing
4. Challenges
5. Clinical Research Examples of AntimiR Therapeutics in Cancer
6. N-Acetylgalactosamine (GalNac) Conjugation Enhancing the Potency of ASO Therapeutics
7. Concluding Remarks
Acknowledgments
Conflicts of Interest
Abbreviations
3′-UTR | 3′-untranslated region |
ASO | antisense oligonucleotide inhibitor |
Bcl-w | B-cell lymphoma-like protein 2 |
Bim | B-cell lymphoma-like protein 11 |
BRCA1 | breast cancer type 1 susceptibility protein |
C/EBPβ | CCAAT/enhancer-binding protein beta |
Cat-ELISA | catalytic enzyme-linked click chemistry assay |
CDX1 | caudal-type homeobox 1 protein |
CRISPR | clustered regularly interspaced short palindromic repeats |
CRMP4 | collapsin response mediator protein 4 |
CYLD | cylindromatosis |
FADD | Fas-associated protein with a death domain |
FOXO3 | forkhead box O3 |
GalNA | N-acetylgalactosamine |
HOXD10 | homeobox D10 |
HSCC | hypopharyngeal squamous cell carcinoma |
KLF4 | Krüppel-like factor 4 |
LIFR | Leukemia Inhibitory Factor (LIF) receptor alpha |
MAPK | mitogen-activated protein kinase |
NF-κB | nuclear factor-κB |
NOTCH1 | neurogenic locus notch homolog protein 1 precursor |
PAX6 | paired box protein |
PDCD4 | programmed cell death 4 |
PI3K | phosphoinositide 3-kinase |
PRKCD | protein kinase C delta type |
PTCH1 | protein patched homolog 1 |
PTEN | phosphatase and tensin homolog |
Rb1 | retinoblastoma |
RECK | reversion-inducing-cysteine-rich protein with kazal motifs |
SHIP1 | SH-2 containing inositol 5′-polyphosphatase 1 |
SIP1 | Smad-interacting protein 1 |
SOCS1 | suppressor of cytokine signaling 1 |
SPRY2 | sprouty homolog 2 |
TNIP1 | Tumor necrosis factor, alpha-induced protein 3 (TNFAIP3)-interacting protein 1 |
TPM1 | tropomyosin α-1 chain |
TP53/P53 | tumor protein p53 |
ZEB1/ZEB2 | zinc finger E-box-binding homeobox 1/-2 |
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OncomiR | Targets | Cancer Type | Ref. |
---|---|---|---|
miR-9 | E-cadherin, LIFR | Breast cancer | [22,23] |
miR-10b | KLF4, HOXD10, TP53, FOXO3, CYLD, PAX6, PTCH1, NOTCH1, | Glioblastoma, esophageal, breast cancer | [24,25,26] |
miR-21 | PTEN, PDCD4, RECK, TPM1 | Glioblastoma, breast, colorectal, lung, pancreas, liver, gastric, cervical, and hematopoietic cancer | [27,28,29,30,31,32] |
miR-106b/93 | PTEN/Akt pathway | Breast cancer | [33] |
miR-125b | P53 | Lung cancer | [34] |
miR-130a | CRMP4 | Gastric cancer | [35] |
miR-155 | SHIP1, PI3K, FADD, CDX1, C/EBPβ | B-cell cancers, glioma | [36,37,38,39,40] |
miR-181a | PRKCD, Bim | Cervical, breast cancer | [41,42] |
miR-200s | ZEB1, ZEB2, SIP1 | Breast, ovarian cancer | [43,44] |
miR-210-3p | SOCS1, TNIP1, NF-κB | Pancreatic cancer | [45] |
miR-221/222 | PTEN | Breast cancer | [46] |
miR-335 | Rb1, Bcl-w | Ovarian cancer | [47,48] |
miR-498 | BRCA1 | Breast cancer | [49] |
miR-504 | P53, CDK6 | HSCC, neuroblastoma | [50,51] |
miR-1810 | PDCD4 | Colorectal cancer | [52] |
miR-1908 miR-224/452 miR-181/340 | PTEN DPYSL2/KRAS KRAS/MECP2 | Glioblastoma Gastric cancer | [53] [54] |
microRNA | Inhibitor Agent | Type of Disease | Investigation Status | Company/Ref |
---|---|---|---|---|
miR-10b | ASO | Glioblastoma | Preclinical | Regulus Therapeutics [108] |
miR-21 | ASO | HCC, fibrosis | Preclinical | Regulus Therapeutics [109,110] |
miR-155 | LNA-modified | T cell lymphoma and mycosis fungoides | Phase I | miRagen Therapeutics [111] |
miR-221 | ASO | Pancreatic carcinoma | Preclinical | Regulus Therapeutics [110] |
miR-122 | LNA-modified | HCV | Phase II | Santaris Pharma [112,113] |
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Nguyen, D.-D.; Chang, S. Development of Novel Therapeutic Agents by Inhibition of Oncogenic MicroRNAs. Int. J. Mol. Sci. 2018, 19, 65. https://doi.org/10.3390/ijms19010065
Nguyen D-D, Chang S. Development of Novel Therapeutic Agents by Inhibition of Oncogenic MicroRNAs. International Journal of Molecular Sciences. 2018; 19(1):65. https://doi.org/10.3390/ijms19010065
Chicago/Turabian StyleNguyen, Dinh-Duc, and Suhwan Chang. 2018. "Development of Novel Therapeutic Agents by Inhibition of Oncogenic MicroRNAs" International Journal of Molecular Sciences 19, no. 1: 65. https://doi.org/10.3390/ijms19010065