Aberrant expressions of miRNA-206 target, FN1, in multifactorial Hirschsprung disease

Gunadi, Gunadi; Budi, Nova Yuli Prasetyo; Kalim, Alvin Santoso; Santiko, Wiwid; Musthofa, Fuad Dheni; Iskandar, Kristy; Makhmudi, Akhmad

doi:10.1186/s13023-018-0973-5

Cited by 20 publications

(17 citation statements)

References 26 publications

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“…A recent study suggested that the expression of THBS1 was modulated by multiple miRNAs (67). Moreover, it's reported that fibronectin 1 ( FN1 ) is crucial to many cellular processes, including cell proliferation, adhesion, migration and differentiation (68, 69), and the expression of FN1 was regulated by miR-1271 (70), miR-9 (71), and miR-206 (72). Similar to previous studies, we identified the negatively regulated miRNA-mRNA pairs in the CS-induced lung cancer, which were implicated in several cancer-related (especially EMT-related) biological process and KEGG pathways in the malignant transformation progress of lung cells induced by CS.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA and mRNA Interaction Network Regulates the Malignant Transformation of Human Bronchial Epithelial Cells Induced by Cigarette Smoke

Wang

Ouyang

et al. 2019

Front. Oncol.

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This study analyzes the correlation and interaction of miRNAs and mRNAs and their biological function in the malignant transformation of BEAS-2B cells induced by cigarette smoke (CS). Normal human bronchial epithelial cells (BEAS-2B) were continuously exposed to CS for 30 passages (S30) to establish an in vitro cell model of malignant transformation. The transformed cells were validated by scratch wound healing assay, transwell migration assay, colony formation and tumorigenicity assay. The miRNA and mRNA sequencing analysis were performed to identify differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) between normal BEAS-2B and S30 cells. The miRNA-seq data of lung cancer with corresponding clinical data obtained from TCGA was used to further identify lung cancer-related DEMs and their correlations with smoking history. The target genes of these DEMs were predicted using the miRDB database, and their functions were analyzed using the online tool “Metascape.” It was found that the migration ability, colony formation rate and tumorigenicity of S30 cells enhanced. A total of 42 miRNAs and 753 mRNAs were dysregulated in S30 cells. The change of expression of top five DEGs and DEMs were consistent with our sequencing results. Among these DEMs, eight miRNAs were found dysregulated in lung cancer tissues based on TCGA data. In these eight miRNAs, six of them including miR-96-5p, miR-93-5p, miR-106-5p, miR-190a-5p, miR-195-5p, and miR-1-3p, were found to be associated with smoking history. Several DEGs, including THBS1, FN1, PIK3R1, CSF1, CORO2B, and PREX1, were involved in many biological processes by enrichment analysis of miRNA and mRNA interaction. We identified the negatively regulated miRNA-mRNA pairs in the CS-induced lung cancer, which were implicated in several cancer-related (especially EMT-related) biological process and KEGG pathways in the malignant transformation progress of lung cells induced by CS. Our result demonstrated the dysregulation of miRNA-mRNA profiles in cigarette smoke-induced malignant transformed cells, suggesting that these miRNAs might contribute to cigarette smoke-induced lung cancer. These genes may serve as biomarkers for predicting lung cancer pathogenesis and progression. They can also be targets of novel anticancer drug development.

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Section: Discussionmentioning

confidence: 99%

MicroRNA and mRNA Interaction Network Regulates the Malignant Transformation of Human Bronchial Epithelial Cells Induced by Cigarette Smoke

Wang

Ouyang

et al. 2019

Front. Oncol.

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“…Numerous studies have reported the regulation of FN1-mediated brosis by miRNAs. Gunadi et al [31] reported that miRNA-206 targeting FN1 is abnormally expressed in multifactorial Hirschsprung's disease and can be used as a potential targeting molecule. Moreover, an interesting phenomenon was found in this study: BSMCs undergo apoptosis after miR-219c-5p is overexpressed.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-219c-5p Regulates Bladder Fibrosis by Targeting FN1

Liu

Ding

et al. 2020

Preprint

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BackgroundWe found that the bladders of multiple sclerosis mice were significantly fibrotic. This study aimed to investigate the relationship between fibronectin 1 (FN1) and bladder fibrosis, as well as the microRNAs involved in FN1 regulation. Methods The degree of bladder smooth muscle fibrosis was observed by immunohistochemistry. In addition, we used quantitative real-time polymerase chain reaction (RT-qPCR) and Western blotting to determine FN1 expression in bladders with different grades of fibrosis. Bioinformatics analysis revealed that miR-199a-3p, miR-219c-5p and miR-3572-3p could inhibit FN1 synthesis. Therefore, miR-199a-3p, miR-219c-5p and miR-3572-3p were overexpressed or knocked down in bladder smooth muscle cells (BSMCs), and the respective transfection and FN1 knockdown efficiencies were detected by RT-qPCR. Only miR-219c-5p overexpression and knockdown produced the expected results. A dual luciferase reporter assay was used to determine the targeting relationship between miR-219c-5p and FN1. Flow cytometry and Cell Counting Kit 8 (CCK8) experiments confirmed that miR-219c-5p reduced FN1 expression and affected the biological activity of smooth muscle cells. Agomir and anagomir of miR-219c-5p were transfected in vivo to observe the change of bladder fibrosis in mice.ResultsWith increasing bladder fibrosis, FN1 expression increased, while miR-199a-3p, miR-219c-5p, and miR-3572-3p expression levels decreased. The RT-qPCR results after transfection showed that only miR-219c-5p could regulate FN1. Indeed, the dual luciferase reporter assay results indicated that miR-219c-5p targeted FN1 directly. CCK8 and cell cycle assays showed that miR-219c-5p overexpression inhibited BSMC proliferation, while miR-219c-5p knockdown promoted BSMC proliferation. An apoptosis assay showed that miR-219c-5p overexpression promoted apoptosis, while miR-219c-5p knockdown inhibited BSMC apoptosis. The agomir and anagomir transfected with miR-219c-5p in vivo found that the bladder fibrosis of the mice in the agomir group was reduced, and the anagomir group was worse.ConclusionsOur findings indicate that FN1 up-regulation and miR-219c-5p down-regulation play an important role in the development of bladder fibrosis, and miR-219c-5p participates in bladder fibrosis by regulating FN1 expression. Thus, a novel antifibrotic function of miR-219c-5p is proposed, which may represent a potential target for the diagnosis and treatment of bladder fibrosis.

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“…A novel anti brotic function of miR-133 was proposed, which represents a potential target for diagnosis and treatment strategies for bladder brosis. Gunadi et al [31] reported that miRNA-206 targeting FN1 is abnormally expressed in multifactorial Hirschsprung's disease and can be used as a potential targeting molecule. Moreover, an interesting phenomenon was found in this study: BSMCs undergo apoptosis after miR-219c-5p is overexpressed.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-219c-5p regulates bladder smooth muscle cell fibrosis by targeting FN1

Liu

Ding

Wang

et al. 2020

Preprint

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Background We found that the bladders of multiple sclerosis mice were significantly fibrotic. This study aimed to investigate the relationship between fibronectin 1 (FN1) and bladder fibrosis, as well as the microRNAs involved in FN1 regulation. Methods The degree of bladder smooth muscle fibrosis was observed by immunohistochemistry. In addition, we used quantitative real-time polymerase chain reaction (RT-qPCR) and Western blotting to determine FN1 expression in bladders with different grades of fibrosis. Bioinformatics analysis revealed that miR-199a-3p, miR-219c-5p and miR-3572-3p could inhibit FN1 synthesis. Therefore, miR-199a-3p, miR-219c-5p and miR-3572-3p were overexpressed or knocked down in bladder smooth muscle cells (BSMCs), and the respective transfection and FN1 knockdown efficiencies were detected by RT-qPCR. Only miR-219c-5p overexpression and knockdown produced the expected results. A dual luciferase reporter assay was used to determine the targeting relationship between miR-219c-5p and FN1. Flow cytometry and Cell Counting Kit 8 (CCK8) experiments confirmed that miR-219c-5p reduced FN1 expression and affected the biological activity of smooth muscle cells. Results With increasing bladder fibrosis, FN1 expression increased, while miR-199a-3p, miR-219c-5p, and miR-3572-3p expression levels decreased. The RT-qPCR results after transfection showed that only miR-219c-5p could regulate FN1. Indeed, the dual luciferase reporter assay results indicated that miR-219c-5p targeted FN1 directly. CCK8 and cell cycle assays showed that miR-219c-5p overexpression inhibited BSMC proliferation, while miR-219c-5p knockdown promoted BSMC proliferation. An apoptosis assay showed that miR-219c-5p overexpression promoted apoptosis, while miR-219c-5p knockdown inhibited BSMC apoptosis. Conclusions Our findings indicate that FN1 upregulation and miR-219c-5p downregulation play an important role in the development of bladder fibrosis, and miR-219c-5p participates in the fibrosis of BSMCs by regulating FN1 expression. Thus, a novel antifibrotic function of miR-219c-5p is proposed, which may represent a potential target for the diagnosis and treatment of bladder fibrosis.

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Aberrant expressions of miRNA-206 target, FN1, in multifactorial Hirschsprung disease

Cited by 20 publications

References 26 publications

MicroRNA and mRNA Interaction Network Regulates the Malignant Transformation of Human Bronchial Epithelial Cells Induced by Cigarette Smoke

MicroRNA and mRNA Interaction Network Regulates the Malignant Transformation of Human Bronchial Epithelial Cells Induced by Cigarette Smoke

MicroRNA-219c-5p Regulates Bladder Fibrosis by Targeting FN1

MicroRNA-219c-5p regulates bladder smooth muscle cell fibrosis by targeting FN1

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