Translational Regulators in Pulmonary Fibrosis: MicroRNAs, Long Non-Coding RNAs, and Transcript Modifications
Abstract
1. Introduction
2. Mechanisms and Insights into Idiopathic Pulmonary Fibrosis
2.1. Profibrotic Signaling Cascades
2.2. Hallmarks of IPF
2.3. Novel Insights for Translational Regulation of Fibrosis
3. Non-Coding RNAS in Translational Regulation of Fibrosis
3.1. Overview of Non-Coding RNAs
3.2. Antifibrotic Canonical miRNAs
3.3. Antifibrotic Noncanonical miRNAs
3.4. Profibrotic Canonical miRNAs
3.5. Profibrotic Noncanonical miRNAs
3.6. lncRNAs in Idiopathic Pulmonary Fibrosis
Name | Category | Target | Function | Reference |
---|---|---|---|---|
miR-326 | Antifibrotic Canonical | TGF-β1 | Downregulates the TGF-β1-induced activation of the canonical and noncanonical pathways and upregulates SMAD7. | [54,55] |
miR-26a | TβRI and SMAD4 | Downregulates TβRI receptor interaction with TbRII and inhibits the nuclear translocation of p-SMAD3 by targeting SMAD4 | [43,57] | |
miR-9-5p | TβRII | Downregulates TGF-β1 signaling | [58,59] | |
miR-18a-5p | TβRII | Downregulates TGF-β1 signaling | [60] | |
miR-19a, -19b, -20a | TβRII | Downregulates TGF-β1 signaling | [61] | |
miR-153 | TβRII | Downregulates TGF-β1 signaling | [62,63] | |
miR-1343 | TβRI and TβRII | Downregulates TGF-β1 signaling | [64] | |
miR-486-5p | SMAD2 | Inhibits downstream SMAD-dependent effector molecules | [65,66] | |
miR-323a-3p | SMAD2 | Inhibits downstream SMAD-dependent effector molecules | [67] | |
miR-29 | SMAD3 | Inhibits the binding of the SMAD3/SMAD2/SMAD4 complex to the target mRNA and inhibits downstream SMAD-dependent effector molecules | [68,69] | |
miR-27a-3p | SMAD2 and SMAD4 | Inhibits downstream SMAD-dependent effector molecules | [70] | |
miR-17~92 | Antifibrotic Noncanonical | DNMT-1 | Inhibits profibrotic genes and has an epigenetic feedback loop with DNMT-1 to regulate the profibrotic genes | [73] |
miR-19a, -19b, -26b | CTGF | Inhibits downstream ET-1 and thrombin profibrotic effects | [7] | |
miR-27b | Gremlin-1 | Downregulates the profibrotic TGF-β1-induced Gremlin-1 signaling cascade | [75] | |
miR-155 | LXRα and KGF | Downregulates the profibrotic effects of LXRα and KGF-induced EMT | [76] | |
miR-26a | HMGA2 | Downregulates HMGA2-induced EMT | [78,79] | |
let-7d | HMGA2 | Downregulates HMGA2-induced EMT | [81] | |
miR-29 | COL1A1 | Inhibits TGF-β1-induced collagen 1 upregulation | [82] | |
miR-21 | Profibrotic Canonical | SMAD7 | Inhibits the antifibrotic effects of SMAD7, the TGF-β1 canonical pathway inhibitor | [84] |
miR-424 | Profibrotic Noncanonical | SMURF2 | Inhibits the antifibrotic regulation of TGF-β1-induced EMT | [89] |
miR-199a-5p | Caveolin-1 | Inhibits the antifibrotic regulation of TGF-β1 signaling | [91] | |
miR-145 | KLF4 | Inhibits the antifibrotic regulation of α-SMA | [92,94] | |
miR-215-5p | BMPR2 | Inhibits the antifibrotic regulation of TGF-β1 signaling | [96] | |
lncRNA PFI | Antifibrotic Noncanonical | miR-328-3p | Inhibits the profibrotic effects of miR-328-3p | [44,97] |
lncRNA-PCF | Profibrotic Noncanonical | miR-344a-5p | Inhibits the antifibrotic effects of miR-344a-5p | [45] |
lncRNA-PFAR | miR-138 | Inhibits the antifibrotic effects of miR-138 | [99] | |
lncRNA-snhg6 | miR-26a | Inhibits the antifibrotic effects of miR-26a | [43] |
4. Transcript Modifications in Translational Regulation
4.1. Alternative Polyadenylation in Fibrosis
4.2. mRNA Chemical Structure Modifications
5. Clinical Potential of RNA-Based Therapies for Fibrosis
6. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
IPF | Idiopathic pulmonary fibrosis |
miRNA | MicroRNA |
lncRNA | Long non-coding RNA |
ECM | Extracellular matrix |
RBPs | RNA-binding proteins |
TGF-β | Transforming growth factor beta |
PDGF | Platelet-derived growth factor |
CTGF | Connective tissue growth factor |
TNF | Tumor necrosis factor |
WNT | Wingless-related integration site |
FGF | Fibroblast growth factor |
EMT | Epithelial–mesenchymal transition |
IL | Interleukin |
INF | Interferon |
ROS | Reactive oxygen species |
MMP | Matrix metalloproteinase |
TIMP | Tissue inhibitor of matrix metalloproteinase |
VEGF | Vascular endothelial growth factor |
LAP | Latency-associated peptide |
RGD | Arginine-glycine-aspartic acid |
NEU3 | Neuraminidase 3 |
TβRI | Transforming growth factor beta receptor 1 |
TβRII | Transforming growth factor beta receptor 2 |
SMAD | Small mothers against decapentaplegic |
MAPK | Mitogen-activated protein kinase |
PI3K | Phosphatidylinositol 3-kinase |
JNK | c-Jun N-terminal kinase |
ERK | Extracellular signal-related kinase |
RAS | Rat sarcoma virus |
RAF | Rapidly accelerating fibrosarcoma |
P-bodies | Processing bodies |
CAT-1 | Cationic amino acid transporter 1 |
LXRα | Liver X receptor |
KGF | Keratinocyte growth factor |
HMGA2 | High mobility group protein A2 |
COL1A1 | Type 1 collagen |
SMURF2 | SMAD ubiquitin regulatory factor |
CAV1 | Caveolin-1 |
KLF4 | Krüppel-like factor 4 |
BMPR2 | Bone morphogenetic protein receptor 2 |
SRSF | Serine/arginine splicing factor 1 |
MAP3K11 | Mitogen-activated protein kinase kinase kinase |
PFAR | Pulmonary fibrosis-associated RNA |
YAP1 | Yes1-associated transcriptional regulator |
APA | Alternative polyadenylation |
CPSF | Cleavage and polyadenylation specificity factor |
CstF | Cleavage stimulation factor |
CF | Cleavage factor |
m6A | N6-methylation of adenosine |
m1A | N1-methylation of adenosine |
m5C | 5-methylcytosine |
m7G | 7-methyguanosine |
A-to-I | Adenosine to inosine |
PM2.5 | Particulate matter diameter of 2.5 μm or less |
siRNA | Small interfering RNA |
hATTR | Hereditary transthyretin-mediated amyloidosis |
AHP | Acute hepatic porphyria |
PH1 | Primary hyperoxaluria type 1 |
HeFH | Heterozygous familial hypercholesterolemia |
ADME | Absorption, distribution, metabolism, and excretion |
FTO | Fat mass and obesity-associated protein |
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Gill, S.K.; Gomer, R.H. Translational Regulators in Pulmonary Fibrosis: MicroRNAs, Long Non-Coding RNAs, and Transcript Modifications. Cells 2025, 14, 536. https://doi.org/10.3390/cells14070536
Gill SK, Gomer RH. Translational Regulators in Pulmonary Fibrosis: MicroRNAs, Long Non-Coding RNAs, and Transcript Modifications. Cells. 2025; 14(7):536. https://doi.org/10.3390/cells14070536
Chicago/Turabian StyleGill, Sumeen Kaur, and Richard H. Gomer. 2025. "Translational Regulators in Pulmonary Fibrosis: MicroRNAs, Long Non-Coding RNAs, and Transcript Modifications" Cells 14, no. 7: 536. https://doi.org/10.3390/cells14070536
APA StyleGill, S. K., & Gomer, R. H. (2025). Translational Regulators in Pulmonary Fibrosis: MicroRNAs, Long Non-Coding RNAs, and Transcript Modifications. Cells, 14(7), 536. https://doi.org/10.3390/cells14070536