The Application of Non-Coding RNAs as Biomarkers, Therapies, and Novel Vaccines in Diseases
Abstract
1. Introduction
Types of RNA | Features and Introduction | References |
---|---|---|
tRNAs | These possess a cloverleaf structure, deliver the correct amino acids to the ribosome, and facilitate the formation of polypeptide chains | [8,9] |
rRNAs | The structural components of the ribosome | [10] |
snRNAs | A class of small RNA molecules in the nucleus of eukaryotic cells that are capable of processing pre-mRNAs | [11] |
snoRNAs | Regulatory factors promoting rRNA maturation | [12] |
TERCs | The RNA component of telomerase, which provides a structural scaffold for the assembly of the telomerase complex | [13,14] |
miRNAs | With a length of approximately 19~24 nucleotides (nts), these serve as post-transcriptional regulatory factors of gene expression | [15] |
circRNAs | These lack free ends and have covalently closed loop structures, and can function as miRNA sponges, RNA-binding protein sponges, and translation regulatory factors | [16,17] |
lncRNAs | With a length exceeding 200 nts, these mediate the post-transcriptional control of signal transduction pathways, translation processes, and gene expression | [18] |
siRNAs | These are primarily involved in RNA interference to regulate gene expression | [19] |
piRNAs | These have diverse functions including gene regulation, transposon suppression, epigenetic programming, and antiviral defense, among others | [20,21] |
2. NcRNAs as Diagnostic Biomarkers
2.1. MiRNAs as Biomarkers
2.2. CircRNAs as Biomarkers
2.3. LncRNAs as Biomarkers
3. NcRNAs in Target Therapy
4. NcRNAs in Novel Vaccines
5. Discussions: Challenges and Opportunities
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Related Diseases | Biofluid | Potential Biomarkers | Target Genes/Pathways/Mechanistic Approaches | References |
---|---|---|---|---|
Thyroid Cancer | Plasma | miR-21 and miR-181a-5p | N/A | [75] |
Liver Cancer | CCM and serum | miR-1247-3p | B4GALT3 | [76] |
Breast Cancer | MSC CCM | miR-21-5p | S100A6 | [77] |
Sepsis | Plasma | miR-1-3p | SERP1 | [78] |
Heart Failure | Plasma | miR-146a | IRAK-1, TRAF6, NOX-4 SMAD4, and TGF-β | [79] |
Myocardial Infarction | Cardiac telocyte CCM | miR-21-5p | CDIP1 | [80] |
Alzheimer’s Disease | Plasma | miR-451a and miR-21-5p | N/A | [81] |
Depressive Disorder | Cortical neuron CCM | miR-138 | SIRT1 | [82] |
Duchenne Muscular Dystrophy | DMD cardiomyocytes CCM | miR-339-5p | MDM2, GSK3A and MAP2K3 | [83] |
Gout | Plasma | miR-3146 | Mediates NETs formation | [84] |
Gastric Cancer | Plasma | circ-RanGAP1 | miR-877-3p/VEGFA axis | [85] |
Hepatocellular Carcinoma | HCC CCM | circRNA-100338 | N/A | [86] |
Glioma | GBM CCM | circNEIL3 | Stabilizing IGF2BP3 | [87] |
Myeloma-Related Myocardial Damage | Serum | circ-G042080 | miR-4268/TLR4 axis | [88] |
Alzheimer’s Disease | Serum | circ_0003611 | miR-885-5p/KREMEN1 axis | [89] |
Type 2 Diabetes | Serum | circGlis3 | Regulates GMEB1 degradation and HSP27 phosphorylation | [90] |
Rheumatoid Arthritis | Plasma | circRNA_09505 | miR-6089/AKT1/NF-κB axis | [91] |
Systemic Lupus Erythematosus | Plasma | hsa_circ_0000479 | Metabolic and the Wnt signaling pathway | [92] |
Graves’ Disease | Plasma | hsa_circ_0090364 | hsa-miR-378a-3p/IL-6ST/IL21R axis | [93] |
Prostate Cancer | Serum | HOXD-AS1 | miR-361-5p/FOXM1 axis | [94] |
Breast Cancer | Serum | SNHG16 | miR-16–5p/SMAD5 axis | [95] |
Bladder Cancer | Urine | lncBCYRN1 | Activates WNT5A/VEGF-C/VEGFR3 feedforward loop | [96] |
Atherosclerosis | HUVEC CCM | lnc-KCNC3-3:1 | JAK1/STAT3 signaling pathway | [97] |
Heart Failure | Plasma | lncRNA-NRF | N/A | [98] |
Parkinson’s Disease | Plasma | lnc-MKRN2-42:1 | N/A | [99] |
Alzheimer’s Disease | Plasma | BACE1-AS | N/A | [100] |
Osteoarthritis | OA CCM | SNHG7 | miR-34a-5p/SYVN1 axis | [101] |
Crohn’s Disease | Plasma | LUCAT1 | NA | [102] |
Diabetic Retinopathy in Type 2 Diabetes | Plasma | NR1F1-AS2 | Moderates EndMT | [103] |
Drugs | Types | Route of Administration | Target Organ | Mechanism of Action | Related Diseases | FDA and/or EMA Approval Year | References |
---|---|---|---|---|---|---|---|
Fomivirsen | ASO | IVT | Eye | Targeting and silencing the mRNA of CMV IE2 protein | CMV retinitis in immunocompromised patients | FDA (1998) EMA (1999) | [104] |
Pegaptanib | Phosphate oligonucleotide aptamer | IVT | Eye | Inhibiting VEGF-165 | nAMD | FDA (2004) | [111] |
Mipomersen | ASO | SC | Liver | Targeting and silencing the mRNA of apolipoprotein B to reduce LDL levels | HoFH | FDA (2013) EMA (2012) | [112] |
Eteplirsen | ASO | IV | Muscle | Targeting and splicing the pre-mRNA of defective DMD dystrophin protein | DMD | FDA (2016) | [113] |
Nusinersen | ASO | ITH | Central nervous system | Targeting and splicing the pre-mRNA of defective SMN protein | SMA | FDA (2016) EMA (2017) | [114] |
Patisiran | siRNA | IV | Liver | Targeting and silencing the mRNA of TTR protein to prevent the production of TTR protein | ATTR amyloidosis | FDA (2018) | [106] |
Inotersen | ASO | SC | Liver | Targeting and silencing the mRNA of TTR protein to prevent the production of TTR protein | ATTR amyloidosis | FDA (2018) EMA (2018) | [115] |
Givosiran | siRNA | SC | Liver | Targeting and silencing the mRNA of ALAS1 to reduce ALAS1 levels | AHP | FDA (2019) EMA (2020) | [116] |
Golodirsen | ASO | IV | Muscle | Targeting the splicing of DMD pre-mRNA (exon 53 skipping) | DMD | FDA (2019) | [117] |
Volanesorsen | ASO | SC | Liver | Targeting and silencing the mRNA of APOC3 to reduce triglyceride production | FCS | EMA (2019) | [118] |
Viltolarsen | ASO | IV | Muscle | Targeting the splicing of DMD pre-mRNA (exon 53 skipping) | DMD | FDA (2020) | [119] |
Lumasiran | siRNA | SC | Liver | Targeting and silencing the mRNA of HAO1 to reduce GO levels | PH1 | FDA (2020) EMA (2020) | [120] |
Casimersen | ASO | IV | Muscle | Targeting the splicing of DMD pre-mRNA (exon 45 skipping) | DMD | FDA (2021) | [121] |
Inclisiran | siRNA | SC | Liver | Targeting PCSK9 to inhibit its synthesis and reduce LDL-C levels | ASCVD | FDA (2021) EMA (2020) | [122] |
Vutrisiran | siRNA | SC | Liver | Targeting and silencing the mRNA of TTR protein to prevent the production of TTR protein | ATTR amyloidosis | FDA (2022) EMA (2022) | [123] |
Nedosiran | siRNA | SC | Liver | Targeting liver LDH mRNA to reduce the expression of LDH | PH1 | FDA (2023) | [124] |
Eplontersen | ASO | SC | Liver | Targeting and silencing the mRNA of TTR protein to prevent the production of TTR protein | ATTR amyloidosis | FDA (2023) | [125] |
Tofersen | ASO | ITH | Muscle | Targeting SOD1 mRNA to reduce the synthesis of SOD1 protein | SOD1-ALS | FDA (2023) EMA (2023) | [126] |
Olezarsen | ASO | SC | Liver | Reducing hepatic synthesis of apolipoprotein C-III to lower plasma triglyceride levels | FCS | FDA (2024) | [127] |
Vaccines | Cyclization Strategy | Delivery | Antigen | References |
---|---|---|---|---|
circRNARBD | Ribozymatic autocatalysis | LNP | SARS-CoV-2 RBD antigen | [149] |
VFLIP-X | T4 RNA ligase | LNP | SARS-CoV-2 spiking protein | [151] |
circRNAOVA-luc-LNP | Ribozymatic autocatalysis | LNP | OVA [257-264]-luciferase | [150] |
CircRNA encoding cytokines | Ribozymatic autocatalysis | LNP | Active IL-15\IL-12\GM-CSF\IFN-α 2b | [152] |
cirA29L, cirA35R, cirB6R, and cirM1R | Ribozymatic autocatalysis | LNP | MPXV proteins A29L, A35R, B6R, and M1R | [153] |
circRNA3×PTPN2 | Ribozymatic autocatalysis | LNP | PTPN2 | [154] |
circRNA-G | Ribozymatic autocatalysis | LNP | Glycoproteins of the RABV vaccine strain SAD-L16 | [155] |
IL12-circRNA | Ribozymatic autocatalysis | LNP | IL-12 | [156] |
circRNA-NA | Ribozymatic autocatalysis | LNP | NA | [157] |
EDIII-Fc circRNA | Ribozymatic autocatalysis | LNP | Dimeric EDIII-Fc fusion | [158] |
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Yang, L.-X.; Li, H.; Cheng, Z.-H.; Sun, H.-Y.; Huang, J.-P.; Li, Z.-P.; Li, X.-X.; Hu, Z.-G.; Wang, J. The Application of Non-Coding RNAs as Biomarkers, Therapies, and Novel Vaccines in Diseases. Int. J. Mol. Sci. 2025, 26, 3055. https://doi.org/10.3390/ijms26073055
Yang L-X, Li H, Cheng Z-H, Sun H-Y, Huang J-P, Li Z-P, Li X-X, Hu Z-G, Wang J. The Application of Non-Coding RNAs as Biomarkers, Therapies, and Novel Vaccines in Diseases. International Journal of Molecular Sciences. 2025; 26(7):3055. https://doi.org/10.3390/ijms26073055
Chicago/Turabian StyleYang, Lu-Xuan, Hui Li, Zhi-Hui Cheng, He-Yue Sun, Jie-Ping Huang, Zhi-Peng Li, Xin-Xin Li, Zhi-Gang Hu, and Jian Wang. 2025. "The Application of Non-Coding RNAs as Biomarkers, Therapies, and Novel Vaccines in Diseases" International Journal of Molecular Sciences 26, no. 7: 3055. https://doi.org/10.3390/ijms26073055
APA StyleYang, L.-X., Li, H., Cheng, Z.-H., Sun, H.-Y., Huang, J.-P., Li, Z.-P., Li, X.-X., Hu, Z.-G., & Wang, J. (2025). The Application of Non-Coding RNAs as Biomarkers, Therapies, and Novel Vaccines in Diseases. International Journal of Molecular Sciences, 26(7), 3055. https://doi.org/10.3390/ijms26073055