Expression profile and bioinformatics analyses of circular RNAs in keloid and normal dermal fibroblasts

Zhang, Zhibin; Yu, Kaihui; Liu, Ougen; Xiong, Yifeng; Yang, Xiongwen; Wang, Shuhua; Zhang, Shulan; Feng, Yueying; Peng, Yating

doi:10.1016/j.yexcr.2019.111799

Cited by 28 publications

(33 citation statements)

References 31 publications

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“…To investigate the expression profile and role of cir-cRNAs KFs, Zhang et al performed high-throughput RNA sequencing technology and screened 411 DE cir-cRNAs with 206 upregulation and 205 downregulation. GO and KEGG pathways enrichment analyses revealed that these DE circRNAs were mainly involved in cell apoptosis, focal adhesion, PI3K-Akt and Rap1 pathway, and metabolic signaling pathway [47]. Similarly, Shi et al performed a circRNA microarray assay to determine cir-cRNA expression in keloid and paired normal skin tissue, finding 52 significantly up-regulated and 24 down-regulated circRNAs in keloid [48].…”

Section: Circrna Expression Profiles In Keloidmentioning

confidence: 99%

“…The expression and abundance of ECM components are altered in KFs, especially the level of collagen. Based on the previous sequencing results, Zhang et al further reported that overexpression of circRNA-0008259 using a lentiviral expression vector, significantly decreased the protein levels of type I and III collagen in KFs, proving that circRNAs were key factors to coordinate collagen hyperplasia and fibroblast proliferation [47]. They speculated that has-circ-0008259/ miR-21-5p might regulate invasion, migration, sphereforming, proliferation, and collagen deposition in KFs [47].…”

Section: Mechanisms Of Circrnas In Keloidmentioning

confidence: 99%

“…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 The genetic pattern in pedigrees with familial keloids revealed that keloid conformed to an autosomal dominant mode of inheritance with incomplete clinical penetrance and variable expression [88].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

“…For example, the up-regulated miR-1225-5p, miR195-5p, miR-513-5p, and the down-regulated miR-6801-3p, miR-4254, and miRNA-412-3p were determined in the serum of patients with keloid through high-throughput sequencing and qRT-PCR verification, advocating that these six serum miRNAs are probable potential diagnostic or predictive biomarkers for further investigation in keloid [33]. Besides, a histopathologic detection found that circRNA-0008259 concentrations were degressive in patients of keloid accompanied by more aggressive collagen deposition in the keloid [47]. Based on characteristics such as highly conserved, stable, resistant to RNase R, and tissue-specific expression, circRNAs might have unparalleled charm and enormous potential in early diagnosis of keloid.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

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Epigenetic modification mechanisms involved in keloid: current status and prospect

Ren

Hou

et al. 2020

Clin Epigenet

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Keloid, a common dermal fibroproliferative disorder, is benign skin tumors characterized by the aggressive fibroblasts proliferation and excessive accumulation of extracellular matrix. However, common therapeutic approaches of keloid have limited effectiveness, emphasizing the momentousness of developing innovative mechanisms and therapeutic strategies. Epigenetics, representing the potential link of complex interactions between genetics and external risk factors, is currently under intense scrutiny. Accumulating evidence has demonstrated that multiple diverse and reversible epigenetic modifications, represented by DNA methylation, histone modification, and non-coding RNAs (ncRNAs), play a critical role in gene regulation and downstream fibroblastic function in keloid. Importantly, abnormal epigenetic modification manipulates multiple behaviors of keloid-derived fibroblasts, which served as the main cellular components in keloid skin tissue, including proliferation, migration, apoptosis, and differentiation. Here, we have reviewed and summarized the present available clinical and experimental studies to deeply investigate the expression profiles and clarify the mechanisms of epigenetic modification in the progression of keloid, mainly including DNA methylation, histone modification, and ncRNAs (miRNA, lncRNA, and circRNA). Besides, we also provide the challenges and future perspectives associated with epigenetics modification in keloid. Deciphering the complicated epigenetic modification in keloid is hopeful to bring novel insights into the pathogenesis etiology and diagnostic/therapeutic targets in keloid, laying a foundation for optimal keloid ending.

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Section: Circrna Expression Profiles In Keloidmentioning

confidence: 99%

Section: Mechanisms Of Circrnas In Keloidmentioning

confidence: 99%

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

See 2 more Smart Citations

Epigenetic modification mechanisms involved in keloid: current status and prospect

Ren

Hou

et al. 2020

Clin Epigenet

View full text Add to dashboard Cite

show abstract

“…A Previous study focused on the regulatory roles of non-coding RNAs during the initiation and progression of keloids (10) and microarray data have indicated aberrantly expressed long non-coding (lnc)RNAs and miRNAs in keloid tissues (14). Furthermore, a previous study reported that circRNAs are aberrantly expressed in keloid fibroblasts compared with healthy controls (15). A complex network of circRNAs and miRNAs are involved in the keloid scarring process (12), suggesting involvement of differentially expressed circRNAs in the scar wound healing process (6).…”

Section: Discussionmentioning

confidence: 99%

Effects of the circ_101238/miR‑138‑5p/CDK6 axis on proliferation and apoptosis keloid fibroblasts

Yang

Li²,

2020

Exp Ther Med

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The formation of keloid scars is normally induced by cutaneous injuries, however, the detailed mechanisms underlying keloid formation remain largely unknown. The present study aimed to investigate the effects of circular RNA_101238 (circ_101238) on the proliferation and apoptosis of keloid fibroblasts and to identify the underlying molecular mechanisms of these effects. Reverse transcription-quantitative (RT-q)PCR was performed to determine the expression levels of circ_101238, microRNA (miRNA/miR)-138-5p and cyclin-dependent kinase 6 (CDK6) in keloids and normal skin tissues. Following transfection with short hairpin (sh)-circ_101238, LV-circ_101238, miR-138-5p mimics, miR-138-5p inhibitors and small interfering (si)-CDK6, cell proliferation was assessed using a cell counting kit-8 assay. Furthermore, cell apoptosis was evaluated via flow cytometric analysis, while a dual-luciferase assay was performed to confirm interactions between circ_101238, miR-138-5p and CDK6. The expression levels of the proliferation marker, CDK6 and apoptosis marker, caspase-3 were determined via RT-qPCR and western blot analyses. The results demonstrated that expression levels of circ_101238 and CDK6 were significantly increased in keloid samples, while miR-138-5p expression was reduced in comparison to normal skin. Furthermore, circ_101238 was demonstrated to bind miR-138-5p, which subsequently targeted CDK6. Proliferative activity and CDK6 expression were significantly decreased in keloid fibroblasts following transfection with sh-circ_101238 or miR-138-5p mimics, while cell apoptosis was markedly increased. Furthermore, co-transfection with miR-138-5p mimics reversed the effects caused by overexpression of circ_101238. Treatment of keloid fibroblasts with si-CDK6 counteracted the biological behavior changes induced by miR-138-5p inhibitors. Additionally, transfection with LV-CDK6 reversed the effects caused by miR-138-5p mimics. Taken together, the results of the present study demonstrated that circ_101238 was upregulated in keloid tissues in comparison with normal tissues and that circ_101238 knockdown inhibited cell proliferation, while promoting apoptosis of keloid fibroblasts via the miR-138-5p/CDK6 axis. These results suggest that circ_101238 may serve as a promising therapeutic candidate for keloid therapy and that circ_101238/miR-138-5p/CDK6 signaling has the potential to regulate the growth of keloid fibroblasts.

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Circular RNA hsa_circ_0043688 serves as a competing endogenous RNA for microRNA‐145‐5p to promote the progression of Keloids via Fibroblast growth factor‐2

Liu

Wang

et al. 2022

Clinical Laboratory Analysis

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Background Keloids are benign fibroproliferative skin tumors. Circular RNA (circRNA) hsa_circ_0043688 has been exhibited to the freakishly expressed in keloid tissues. Here, we aimed to investigate the regulatory network of hsa_circ_0043688 in the pathological process of keloid. Methods Hsa_circ_0043688, microRNA‐145‐5p (miR‐145‐5p), and Fibroblast growth factor‐2 (FGF2) level were detected using RT‐qPCR. Cell viability, proliferation, apoptosis, invasion, and migration were investigated using Cell Counting Kit‐8 (CCK‐8), 5‐ethynyl‐2′‐deoxyuridine (EdU), flow cytometry, transwell, and wound healing assays, respectively. Western blot analysis of protein levels of FGF2, CyclinD1, Collagen I, and Collagen III. After the prediction of Circinteractome and Starbase, their interaction was verified based on a dual‐luciferase reporter and RIP assays. Results Increased hsa_circ_0043688 and FGF2, and decreased miR‐145‐5p in keloids samples and fibroblasts were found. Also, hsa_circ_0043688 absence hindered proliferation, invasion, migration, and boost apoptosis of keloid fibroblasts. In mechanism, hsa_circ_0043688 modulated FGF2 content via sponging miR‐145‐5p. Conclusion Hsa_circ_0043688 knockdown inhibited cell growth and metastasis of keloid fibroblasts via miR‐145‐5p/FGF2, providing a new mechanism to understand the keloid progression.

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Expression profile and bioinformatics analyses of circular RNAs in keloid and normal dermal fibroblasts

Cited by 28 publications

References 31 publications

Epigenetic modification mechanisms involved in keloid: current status and prospect

Epigenetic modification mechanisms involved in keloid: current status and prospect

Effects of the circ_101238/miR‑138‑5p/CDK6 axis on proliferation and apoptosis keloid fibroblasts

Circular RNA hsa_circ_0043688 serves as a competing endogenous RNA for microRNA‐145‐5p to promote the progression of Keloids via Fibroblast growth factor‐2

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