Table 4.
Mechanisms and clinical value of ncRNAs in keloid
| ncRNAs | Expression | Target gene | Mechanism | Clinical value | Ref |
|---|---|---|---|---|---|
| miR-152-3p | Upregulation | FOXF1 | MiR-152-3p regulated cell proliferation, invasion and ECM expression through targeting FOXF1 in KFs | A novel and promising molecular target for keloid treatment | [63] |
| miRNA-31 | Upregulation | HIF1AN | MiRNA-31 regulated proliferation, apoptosis, and cell cycle of keloid-derived fibroblasts by mediating HIF1AN/VEGF signaling pathway | A promising therapeutic target in keloid scarring | [64] |
| miR-181a | Upregulation | PHLPP2 | MiR-181a targeted PHLPP2 to augment AKT signaling and regulate proliferation and apoptosis in human KFs | A therapeutic target for treatment of keloids | [65] |
| miR-21 | Upregulation | TGF-β1 | TGF-β1 increased the promoting actions of miR-21 on the proliferation and migration of KFs while attenuating apoptosis | A novel evidence on a theoretical basis for keloid treatment | [66] |
| miR-21 | Upregulation | TGF-β1 | TGF-β1 promoted KFs proliferation and transdifferentiation via up-regulation of miR-21 and PTENAKT signaling pathway | A potential theoretical basis for clinical treatment of keloids | [67] |
| miR-21-5p | Upregulation | PTEN | MiR-21-5p increased the migration, invasion, sphere-forming abilities of keloid keratinocytes, the phenotype of EMT, and cells stemness | A novel therapeutic targets for keloids | [68] |
| miR-21 | Upregulation | FasL | MiR-21 regulated the apoptosis of KFs by caspase-8 and mitochondrial-mediated apoptotic signaling pathway | A therapeutic target for keloids | [69] |
| miR-21 | Upregulation | Smad7 | MiR-21 promoted Col1A1 and Col3A1 expression in keloid-derived fibroblast | A potential target for keloid treatment | [70] |
| miR-196a | Downregulation | COL1A1 and COL3A1 | MiR-196a downregulation increased the collagens expression in KFs | A new therapeutic target for keloid lesions | [71] |
| miR-200b | Downregulation | N/A | MiR-200b inhibited the cell proliferation and promoted apoptosis of fibroblast via TGF-β1/a-SMA signaling | A useful target for hypertrophic scarring management | [72] |
| miR-29a | Downregulation | COL3A1 | MiR-29a markedly reduced Type I and type III collagen mRNA and protein levels | A novel marker for keloids | [73] |
| miR-205-5p | Downregulation | VEGF | MiR-205-5p overexpression induced the cell apoptosis, and inhibited the cell invasion and migration ability in KFs | A potential therapy for prevention and treatment of keloids | [74] |
| miR-141-3p | Downregulation | GAB1 | MiR-141-3p inhibited fibroblast proliferation and migration in keloids | A useful target for keloid management | [75] |
| miR-188-5p | Downregulation | N/A | MiR-1224-5p regulated proliferation, apoptosis, and invasion via the TGF-β1/Smad3 signaling pathway in KFs | A possible new therapeutic strategy for keloids | [76] |
| miR-203 | Downregulation | EGR1 and FGF2 | MiR-203 overexpression resulted in a significant decrease in proliferation, invasion, and ECM production in KFs | A potential role in preventing and treating keloids | [77] |
| miR-152-5p | Downregulation | Smad3 | MiR-152-5p inhibited proliferation and migration and promotes apoptosis via the Erk1/2 and Akt pathways in human KFs | A potential therapeutic target of keloids | [78] |
| miR‑637 | Downregulation | Smad3 | MiR-637 inhibited KFs proliferation and metastasis | A promising therapeutic target in keloids | [79] |
| miR-188-5p | Downregulation | N/A | MiR-188-5p regulated proliferation and invasion via PI3K/Akt/MMP-2/9 signaling in keloids | A potential prognostic marker and therapeutic target for keloids | [80] |
| miR-4417 | Downregulation | CyclinD1 | MiR-4417 suppressed keloid fibrosis growth by inhibiting CyclinD1 | A potential therapeutic target in keloids | [81] |
| miR-1-3p and miR-214-5p | Downregulation | TM4SF1 | MiR-1-3p and miR-214-5p inhibited cell proliferation, migration, and induced apoptosis in HKFs | A potential targets in therapies for keloids | [82] |
| lncRNA-H19 | Upregulation | miR-29a | LncRNA-H19 affected the viability and apoptosis of KFs through COL1A1 signaling | LncRNA-H19 was expected to allow for development of keloid-targeted treatments | [102] |
| lncRNAHOXA11-AS | Upregulation | miR-124-3p | High expression of HOXA11-AS essentially inhibited cell apoptosis and promoted fibroblast-induced angiogenesis via PI3K/Akt signaling pathway | A novel target for keloid therapy | [84] |
| lncRNA CAS1 | Upregulation | N/A | LncRNA-CAS1 promoted calcium channel protein and type I collagen expression, and had a positive effect on cell migration in human KFs | A new therapeutic target for keloids | [85] |
| lncRNA-ATB | Upregulation | miR-200c | Knockdown of lncRNA-ATB decreased autocrine secretion of TGF-β2 | Potential biomarkers and targets for novel diagnostic and therapeutic approaches for keloids | [86] |
| circRNA_0008259 | Downregulation | N/A | Overexpression of circRNA_0008259 inhibited type I and collagen expression | Act as biomarkers of keloid | [47] |
| circCOL3A1-859267 | Downregulation | miR-29c | circCOL3A1-859267 regulated type I collagen expression in fibroblasts | NA | [87] |
The ncRNAs (miRNAs, lncRNAs, and circRNAs) are crucial in the coordination of KFs function and gene transcription, as well as in the pathogenesis and the prognostic value of keloid. ncRNAs non-coding RNAs, miRNAs microRNAs, lncRNAs long non-coding RNAs, circRNAs circular RNAs