Long non-coding RNA HOXA11-AS induces type I collagen synthesis to stimulate keloid formation via sponging miR-124-3p and activation of Smad5 signaling

Jin, Jun; Zhai, Hong-feng; Jia, Zhenhua; Luo, Xiao‐Hua

doi:10.1152/ajpcell.00319.2018

Cited by 37 publications

(33 citation statements)

References 30 publications

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“…In our analysis, many genes such as SMAD5, CAV1, JAG1, ROCK1 and STAT3 were positively predicted as downstream targets of miR-124, which was regarded as a potential miRNA binding site of hsa_circ_0029633. Previous studies have demonstrated that miR-124 plays a key role in multiple diseases including IPF by targeting SMAD5, CAV1, JAG1, ROCK1 or STAT3 [37][38][39][40][41][42], which is consistent with our findings. Previous studies have also shown that FOXC1 and HSPA1A are direct target genes of miR-223 [43,44], and these genes contribute to the pathogenesis of IPF via activating various signaling pathways.…”

Section: Discussionsupporting

confidence: 93%

Potential function and molecular mechanism of circRNAs involved in idiopathic pulmonary fibrosis

Wang²,

Tao³

et al. 2020

Preprint

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Background: Recent studies have found a regulatory role of circular RNAs (circRNAs) in the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, the function and underlying molecular mechanism of circRNAs involved in IPF are uncertain and incomplete. This study aimed to further provide some critical information for the circRNA function in IPF using bioinformatic analysis.Methods: We searched in the NCBI (National Center for Biotechnology Information) Gene Expression Omnibus (GEO) database to find the circRNA expression profiles of human IPF. The microarray data GSE102660 was obtained and differentially expressed circRNAs were identified through R software.Results: 6 significantly up-regulated and 13 significantly down-regulated circRNAs were identified involved in the pathogenesis of IPF. The binding sites of miRNAs for each differentially expressed circRNA were also predicted and circRNA-miRNA-mRNA networks were constructed for the most upregulated hsa_circ_0004099 and down-regulated hsa_circ_0029633. In addition, GO and KEGG enrichment analysis revealed the molecular function and enriched pathways of the target genes of circRNAs in IPF.Conclusion: These findings suggest that candidate circRNAs might serve an important role in the pathogenesis of IPF. Therefore, these circRNAs might be potential biomarkers for diagnosis and promising targets for treatment of IPF, which still need further verification in vivo and in vitro.

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Section: Discussionsupporting

confidence: 93%

Potential function and molecular mechanism of circRNAs involved in idiopathic pulmonary fibrosis

Wang²,

Tao³

et al. 2020

Preprint

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“…Similarly, previous studies have reported that non-coding RNAs, including miR-152-3p, miR-21 and miR-203 are differently expressed in keloid samples, which may contribute to the formation of keloids ( 18-20 ). Furthermore, lncRNA HOXA11-AS has been demonstrated to regulate the progression of keloids via miR-124-3p/Smad5 signaling ( 21 ). A recent study reported the involvement of the circRNAs and miRNAs regulatory networks during keloid scarring ( 22 ).…”

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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“…Liang et al (26) also reported that miR-124 may regulate the EMT process by targeting snail family transcriptional repressor 2 to promote breast cancer metastasis, while Cui et al (27) suggested that miR-124 may induce hepatocellular carcinoma metastasis by targeting Slug. Additionally, homeoboxA11 has been shown to induce the formation of type I collagen in scars via the activation of miR-124-3p and the SMAD signaling pathway in the cavernous body (28). Thus, miR-124 contributes to the formation of fibrotic tissue in a variety of diseases by responding to the TGF-β and EMT signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Detection of microRNA expression levels based on microarray analysis for classification of idiopathic pulmonary fibrosis

Zheng

et al. 2020

Exp Ther Med

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The etiology and pathophysiological mechanisms of idiopathic pulmonary fibrosis (IPF) are yet to be fully elucidated; however, mining of disease-related microRNAs (miRNAs/miRs) has improved the understanding of the progression of IPF. The aim of the current study was to screen miRNAs associated with IPF using three mathematical algorithms: One-way ANOVA, least absolute shrinkage and selector operation (LASSO) and support vector machinerecursive feature elimination (SVM-RFE). Using ANOVA, three miRNAs and two miRNAs were selected with opposite expression patterns in moderate and severe IPF, respectively. In total, two algorithms, LASSO and SVM-RFE, were used to perform feature selection of miRNAs. miRNAs from patients were also extracted from formalin-fixed paraffin-embedded tissues and detected using reverse transcription-quantitative PCR (RT-qPCR). The intersection of the three algorithms (ANOVA, LASSO and SVM-RFE) was taken as the final result of the miRNA candidates. Three miRNA candidates, including miR-124, hsa-miR-524-5p and hsa-miR-194 were therefore used as biomarkers. The receiver operating characteristic model demonstrated favorable discrimination between IPF and control groups, with an area under the curve of 78.5%. Moreover, RT-qPCR results indicated that miR-124, hsa-miR-524-5p, hsa-miR-194 and hsa-miR-133a were differentially expressed between patients with IPF and age-matched men without fibrotic lung disease. The target genes of these miRNAs were further predicted and Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed. Collectively, the present results suggested that the identified miRNAs associated with IPF may be useful biomarkers for the diagnosis of this disease.

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Long non-coding RNA HOXA11-AS induces type I collagen synthesis to stimulate keloid formation via sponging miR-124-3p and activation of Smad5 signaling

Cited by 37 publications

References 30 publications

Potential function and molecular mechanism of circRNAs involved in idiopathic pulmonary fibrosis

Potential function and molecular mechanism of circRNAs involved in idiopathic pulmonary fibrosis

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

Detection of microRNA expression levels based on microarray analysis for classification of idiopathic pulmonary fibrosis

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