scholarly journals Long non-coding RNA H19 deficiency ameliorates bleomycin-induced pulmonary inflammation and fibrosis

2020 ◽  
Author(s):  
XIAOYU WAN ◽  
XINBEI TIAN ◽  
JUN DU ◽  
YING LU ◽  
YONGTAO XIAO
Keyword(s):  
Pulmonary Fibrosis ◽  
Pulmonary Inflammation ◽  
Chain Reaction ◽  
Potential Therapeutic Target ◽  
Qrt Pcr ◽  
Stat3 Signaling ◽  
Non Coding Rna ◽  
Poor Understanding ◽  
Polymerase Chain ◽  
Long Non Coding Rna

Abstract Background: The poor understanding of pathogenesis in idiopathic pulmonary fibrosis (IPF) impaired development of effective therapeutic strategies. The aim of the current study is to investigate the roles of long non-coding RNA H19 (lncRNA H19) in the pulmonary inflammation and fibrosis of IPF. Methods: Bleomycin was used to induce pulmonary inflammation and fibrosis in mice. The mRNAs and proteins expression in lung tissues was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. H19 knockout (H19-/-) mice were generated by CRISPR/Cas9.Results: The expression of H19 mRNA was up-regulated in fibrotic lungs patients with IPF as well as in lungs tissues that obtained from bleomycin-treated mice. H19-/- mice suppressed bleomycin-mediated pulmonary inflammation and inhibited the Il6/Stat3 signaling. H19 deficiency ameliorated bleomycin-induced pulmonary fibrosis and repressed the activation of TGF-β/Smad and S1pr2/Sphk2 in the lungs of bleomycin-treated mice. Conclusions: Our data suggests that H19 is a profibrotic lncRNA and a potential therapeutic target for IPF.

scholarly journals Long non-coding RNA H19 deficiency ameliorates bleomycin-induced pulmonary inflammation and fibrosis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoyu Wan ◽  
Xinbei Tian ◽  
Jun Du ◽  
Ying Lu ◽  
Yongtao Xiao
Keyword(s):  
Pulmonary Fibrosis ◽  
Pulmonary Inflammation ◽  
Chain Reaction ◽  
Potential Therapeutic Target ◽  
Qrt Pcr ◽  
Stat3 Signaling ◽  
Non Coding Rna ◽  
Poor Understanding ◽  
Polymerase Chain ◽  
Long Non Coding Rna

Abstract Background The poor understanding of pathogenesis in idiopathic pulmonary fibrosis (IPF) impaired development of effective therapeutic strategies. The aim of the current study is to investigate the roles of long non-coding RNA H19 (lncRNA H19) in the pulmonary inflammation and fibrosis of IPF. Methods Bleomycin was used to induce pulmonary inflammation and fibrosis in mice. The mRNAs and proteins expression in lung tissues was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. H19 knockout (H19−/−) mice were generated by CRISPR/Cas9. Results The expression of H19 mRNA was up-regulated in fibrotic lungs patients with IPF as well as in lungs tissues that obtained from bleomycin-treated mice. H19−/− mice suppressed bleomycin-mediated pulmonary inflammation and inhibited the Il6/Stat3 signaling. H19 deficiency ameliorated bleomycin-induced pulmonary fibrosis and repressed the activation of TGF-β/Smad and S1pr2/Sphk2 in the lungs of bleomycin-treated mice. Conclusions Our data suggests that H19 is a profibrotic lncRNA and a potential therapeutic target for IPF.

scholarly journals Long non-coding RNA H19 deficiency ameliorates bleomycin-induced pulmonary inflammation and fibrosis

2020 ◽  
Author(s):  
XIAOYU WAN ◽  
XINBEI TIAN ◽  
JUN DU ◽  
YING LU ◽  
YONGTAO XIAO
Keyword(s):  
Pulmonary Fibrosis ◽  
Pulmonary Inflammation ◽  
Chain Reaction ◽  
Potential Therapeutic Target ◽  
Qrt Pcr ◽  
Stat3 Signaling ◽  
Non Coding Rna ◽  
Poor Understanding ◽  
Polymerase Chain ◽  
Long Non Coding Rna

Abstract Background: The poor understanding of pathogenesis in idiopathic pulmonary fibrosis (IPF) impaired development of effective therapeutic strategies. The aim of the current study is to investigate the roles of long non-coding RNA H19 (lncRNA H19) in the pulmonary inflammation and fibrosis of IPF. Methods: Bleomycin was used to induce pulmonary inflammation and fibrosis in mice. The mRNAs and proteins expression in lung tissues was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. H19 knockout (H19-/-) mice were generated by CRISPR/Cas9.Results: The expression of H19 mRNA was up-regulated in fibrotic lungs patients with IPF as well as in lungs tissues that obtained from bleomycin-treated mice. H19-/- mice suppressed bleomycin-mediated pulmonary inflammation and inhibited the Il6/Stat3 signaling. H19 deficiency ameliorated bleomycin-induced pulmonary fibrosis and repressed the activation of TGF-β/Smad and S1pr2/Sphk2 in the lungs of bleomycin-treated mice. Conclusions: Our data suggests that H19 is a profibrotic lncRNA and a potential therapeutic target for pulmonary fibrosis.

scholarly journals Long non-coding RNA H19 deficiency ameliorates bleomycin-induced pulmonary inflammation and fibrosis

2020 ◽  
Author(s):  
XIAOYU WAN ◽  
XINBEI TIAN ◽  
JUN DU ◽  
YING LU ◽  
YONGTAO XIAO
Keyword(s):  
Pulmonary Fibrosis ◽  
Pulmonary Inflammation ◽  
Chain Reaction ◽  
Potential Therapeutic Target ◽  
Stat3 Signaling ◽  
Non Coding Rna ◽  
Poor Understanding ◽  
Polymerase Chain ◽  
Long Non Coding Rna

Abstract Background: The poor understanding of pathogenesis in idiopathic pulmonary fibrosis (IPF) impaired development of effective therapeutic strategies. The aim of the current study is to investigate the roles of long non-coding RNA H19 (lncRNA H19) in the pathogenesis of IPF. Methods: Bleomycin was used to induce pulmonary inflammation and fibrosis in mice. The mRNAs and proteins expression in lung tissues was determined by quantitative real-time polymerase chain reaction and western blot. H19 knockout (H19-/-) mice were generated by CRISPR/Cas9 and used to investigate the roles of H19 in the pulmonary inflammation and fibrosis in vivo.Results: The expression of H19 mRNA was up-regulated in fibrotic lungs patients with IPF as well as in lungs tissues that obtained from bleomycin-treated mice. H19-/- mice suppressed bleomycin-mediated pulmonary inflammation and inhibited the Il6/Stat3 signaling. H19 deficiency ameliorated bleomycin-induced pulmonary fibrosis and repressed the activation of TGF-β/Smad and S1pr2/Sphk2 in the lungs of bleomycin-treated mice. Conclusions: Our data suggests that H19 is a profibrotic lncRNA and a potential therapeutic target for pulmonary fibrosis.

scholarly journals Long non-coding RNA H19 deficiency ameliorates bleomycin-induced pulmonary inflammation and fibrosis

2020 ◽  
Author(s):  
XIAOYU WAN ◽  
XINBEI TIAN ◽  
JUN DU ◽  
YING LU ◽  
YONGTAO XIAO
Keyword(s):  
Pulmonary Fibrosis ◽  
Pulmonary Inflammation ◽  
Chain Reaction ◽  
Potential Therapeutic Target ◽  
Stat3 Signaling ◽  
Non Coding Rna ◽  
Poor Understanding ◽  
Polymerase Chain ◽  
Long Non Coding Rna

Abstract Background: The poor understanding of pathogenesis in idiopathic pulmonary fibrosis (IPF) impaired development of effective therapeutic strategies. The aim of the current study is to investigate the roles of long non-coding RNA H19 (lncRNA H19 ) in the pathogenesis of IPF. Methods: Bleomycin was used to induce pulmonary inflammation and fibrosis in mice. The mRNAs and proteins expression in lung tissues was determined by quantitative real-time polymerase chain reaction and western blot. H19 knockout ( H19 -/- ) mice were generated by CRISPR/Cas9 and used to investigate the roles of H19 in the pulmonary inflammation and fibrosis in vivo . Results: The expression of H19 mRNA was up-regulated in fibrotic lungs patients with IPF as well as in lungs tissues that obtained from bleomycin-treated mice. H19 -/- mice suppressed bleomycin-mediated pulmonary inflammation and inhibited the Il6/Stat3 signaling. H19 deficiency ameliorated bleomycin-induced pulmonary fibrosis and repressed the activation of TGF-β/Smad and S1pr2/Sphk2 in the lungs of bleomycin-treated mice. Conclusions : Our data suggests that H19 is a profibrotic lncRNA and a potential therapeutic target for pulmonary fibrosis.

scholarly journals Long non-coding RNA H19 deficiency ameliorates bleomycin-induced pulmonary inflammation and fibrosis

2020 ◽  
Author(s):  
Xiaoyu Wan ◽  
Xinbei Tian ◽  
Jun Du ◽  
Ying Lu ◽  
Yongtao Xiao
Keyword(s):  
Pulmonary Fibrosis ◽  
Pulmonary Inflammation ◽  
Stat3 Signaling ◽  
Non Coding Rna ◽  
Polymerase Chain ◽  
Lung Regeneration ◽  
Long Non Coding Rna ◽  
Mouse Lungs

Abstract Background: The limited understanding of pathogenesis in idiopathic pulmonary fibrosis (IPF) impaired development of effective therapeutic strategies.The aim of this study was to investigate the role of long non-coding RNA H19 (lncRNA H19) in the progression of IPF. Methods: Bleomycin was used to induce pulmonary fibrosis in mice. The mRNAs and proteins expression in lung tissues with bleomycin-induced pulmonary fibrosis was determined by quantitative real-time polymerase chain reaction and western blot. H19 deficiency (H19-/-) were generated by CRISPR/Cas9 and were used to investigate the roles of H19 in the pulmonary inflammation and fibrosis in vivo.Results: The expression of H19 was up-regulated in fibrotic lungs patients with IPF and mouse lungs obtained from bleomycin-treated mice. H19 deficiency reduced bleomycin-induced pulmonary inflammation and inhibited the activation of Il6/Stat3 signaling. H19 deficiency ameliorated bleomycin-induced pulmonary fibrosis and repressed the activation of TGFβ-Smad and S1pr2/Sphk2 in the lungs of bleomycin-treated mice. H19 depletion attenuated the lung regeneration and reduced expression of activated Egfr. Conclusions: Our data suggest that H19 is a profibrotic lncRNA and a potential therapeutic target for pulmonary fibrosis.

scholarly journals MicroRNA-425-5p modulates osteoporosis by targeting annexin A2

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Guanghua Chen ◽  
Guizhi Huang ◽  
Han Lin ◽  
Xinyou Wu ◽  
Xiaoyan Tan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Cell Apoptosis ◽  
Chain Reaction ◽  
Potential Therapeutic Target ◽  
Treatment Of Osteoporosis ◽  
Qrt Pcr ◽  
Proliferation And Differentiation ◽  
Marrow Mesenchymal Stem Cells ◽  
Polymerase Chain

Abstract Background Studies have shown that the decrease of osteogenic differentiation of bone marrow mesenchymal stem cells (MSC) is an important mechanism of osteoporosis. The object of this study was to explore the role and mechanism of microRNA miR-425-5p in the differentiation of MSC. Methods The expression of miR-425-5p in MSC was detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Cell proliferation, cell cycle and apoptosis were detected by CCK-8 colorimetry and flow cytometry. The expression of TNF were detected by ELISA. Results Our data show that MiR-425-5p could modulate TNF-induced cell apoptosis, proliferation, and differentiation. ANXA2 is also the target of miR-425-5p and ANXA2 was involved in TNF-induced MSC cell apoptosis, proliferation, and differentiation. In addition, MiR-425-5p enhanced osteoporosis in mice. Conclusion MiR-425-5p might serve as a potential therapeutic target for the treatment of osteoporosis.

scholarly journals MicroRNAs και Long non-coding RNAs ως βιοδείκτες στην πρόβλεψη της φαρμακευτικής ανταπόκρισης ασθενών με μεταστατικό ορθοκολικό καρκίνο

2021 ◽  
Author(s):  
Δήμητρα-Ιωάννα Λαμπροπούλου
Keyword(s):  
Fragment Length Polymorphism ◽  
Chain Reaction ◽  
Specific Pcr ◽  
Non Coding Rna ◽  
Allele Specific ◽  
Non Coding Rnas ◽  
Polymerase Chain ◽  
Long Non Coding Rna ◽  
Allele Specific Pcr ◽  
Restriction Fragment Length

Σκοπός της παρούσας διδακτορικής διατριβής ήταν η διερεύνηση πιθανής συσχέτισης ανάμεσα στο προφίλ έκφρασης non coding RNA μονονουκλεοτιδικών πολυμορφισμών και στην ανταπόκριση στη θεραπεία ασθενών με μεταστατικό καρκίνο παχέος εντέρου-ορθού (ΚΠΕ-Ο) που λαμβάνουν χημειοθεραπευτικά σχήματα που περιλαμβάνουν την ιρινοτεκάνη, με απώτερο σκοπός την ανάδειξη νέων βιοδεικτών.Ασθενείς, Υλικά και Μέθοδοι: Η διερεύνηση των microRNA πολυμορφισμών έγινε σε γενωμικό DNA που απομονώθηκε από περιφερικό αίμα 105 ασθενών, ενώ η διερεύνηση των lncRNA πολυμορφισμών σε γενωμικό DNA που απομονώθηκε από περιφερικό αίμα 98 ασθενών με μεταστατικό ΚΠΕ-Ο. Η απομόνωση του γενωμικού DNA πραγματοποιήθηκε με τη χρήση του NucleoSpin Blood Kit (Macherey-Nagel, Germany). Η γονοτύπηση των πολυμορφισμών rs11134527 miR-218 και rs1834306 miR-100 έγινε με την τεχνική PCR (Polymerase chain Reaction)-RFLP (Restriction Fragment Length Polymorphism). H γονοτύπηση long non-coding RNA πολυμορφισμών HOTAIR rs4759314 και MALAT1 rs3200401 πραγματοποιήθηκε με την τεχνική AS (Allele Specific)-PCR. Ακολούθησε στατιστική ανάλυση κατά την οποία οι συχνότητες των γονοτύπων συγκρίθηκαν με τη δοκιμασία χ2 με διόρθωση κατά Yates (Yate’s correction). Η απλοτυπική ανάλυση πραγματοποιήθηκε με τη χρήση της διαδικτυακής πλατφόρμας https://www.snpstats.net/preproc.php. Αποτελέσματα: Υπομελέτη microRNA πολυμορφισμών-Δεν παρατηρήθηκαν στατιστικά σημαντικές συσχετίσεις ανάμεσα στην αντικειμενική ανταπόκριση και τους υπο μελέτη γονότυπους. Ωστόσο, οι GA και ΑΑ miR-218 rs11134527 και οι CT και TT του miR-100 rs1834306 συσχετίστηκαν στατιστικώς σημαντικά με την υποομάδα ασθενών που εμφάνισε πρόοδο νόσου. Δεν παρατηρήθηκαν στατιστικώς σημαντικές συσχετίσεις ανάμεσα τους υπό μελέτη γονότυπους και τον κίνδυνο εμφάνισης τοξικότητας. Οι γονότυποι GA και AA rs11134527 συνδέθηκαν στατιστικά περισσότερο με χειρότερη πρόγνωση. Ομοίως, οι rs1834306 CT και TT συσχετίστηκαν με στατιστικά μικρότερη συνολική επιβίωση. Από πολυπαραγοντική ανάλυση αναφορικά με την επίδραση στην επιβίωση, προκύπτει ότι η παρουσία των rs1834306 CT και TT γονοτύπων μπορεί να θεωρηθεί ως ανεξάρτητος προγνωστικός παράγοντας συνολικής επιβίωσης. Υπομελέτη Long non-coding RNA πολυμορφισμών- Δεν ανευρέθηκαν σημαντικές συσχετίσεις μεταξύ της ανταπόκρισης και τους rs4759314 και rs3200401 γονότυπους και απλότυπους. Φορείς των AG και GG γονοτύπων του rs4759314 φαίνεται ότι είναι στατιστικά πιθανότερο να φέρουν KRAS μεταλλάξεις. Ανευρέθηκε μια στατιστικά σημαντική συσχέτιση μεταξύ φορέων των rs3200401 CT/TT αλληλόμορφων και ανάπτυξης τοξικότητας. Δεν παρατηρήθηκαν στατιστικώς σημαντικές συσχετίσεις μεταξύ του πολυμορφισμού rs4759314 και συνολικής επιβίωσης. Ωστόσο, οι CT και TT γονότυποι του rs3200401 συνδέθηκαν σημαντικά με μικρότερη συνολική επιβίωση.Συμπεράσματα: Στην παρούσα μελέτη φάνηκε για πρώτη φορά πιθανή συσχέτιση μεταξύ των πολυμορφισμών miR-218 rs11134527 και miR-100 rs1834306 και ανταπόκρισης σε θεραπευτικά σχήματα που περιλαμβάνουν ιρινοτεκάνη. Επίσης, φάνηκε ότι φορείς του μεταλλαγμένου Α αλληλόμορφου του miR-218 rs11134527 και του μεταλλαγμένου T αλληλόμορφου του miR-100 rs1834306 είναι πιθανό να μην ανταποκριθούν σε σχήματα με ιρινοτεκάνη. Επιπλέον, οι GA/AA γονότυποι του rs11134527 και οι CT/TT του rs1834306 CT/TT συσχετίστηκαν στατιστικώς σημαντικά με μικρότερη συνολική επιβίωση. Αναφορικά με τον πολυμορφισμό rs3200401 MALAT1, φάνηκε για πρώτη φορά πιθανή συσχέτιση με την ανάπτυξη τοξικότητας και τη συνολική επιβίωση των ασθενών. Τέλος, η ανάλυση γονιδιακής έκφρασης έδειξε ότι φορείς του μεταλλαγμένου G αλληλόμορφου του rs4759314 HOTAIR είναι πιθανό να φέρουν επίσης KRAS μεταλλάξεις. Τα αποτελέσματα της μελέτης μας πρέπει να ενισχυθούν από μεγαλύτερης κλίμακας έρευνες με μεγαλύτερα πληθυσμιακά δείγματα, ώστε οι εν λόγω πολυμορφισμοί να μπορέσουν να χρησιμοποιηθούν για θεραπευτικούς και προγνωστικούς σκοπούς στο μέλλον.

scholarly journals Long non-coding RNA LINC00630 facilitates hepatocellular carcinoma progression through recruiting transcription factor E2F1 to up-regulate cyclin-dependent kinase 2 expression

2021 ◽  
pp. 096032712110387
Author(s):  
Jian Kang ◽  
Xu Huang ◽  
Weiguo Dong ◽  
Xueying Zhu ◽  
Ming Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Promoter Region ◽  
Cell Cycle Progression ◽  
Cyclin Dependent Kinase ◽  
Chain Reaction ◽  
Cycle Progression ◽  
Non Coding Rna ◽  
Polymerase Chain ◽  
Long Non Coding Rna

This study is aimed to investigate the role of long non-coding RNA 630 (LINC00630) in hepatocellular carcinoma (HCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine LINC00630 expression in HCC cell lines and tissues. After LINC00630 was overexpressed or depleted in HCC cell lines, cell counting kit-8 (CCK-8) assay, BrdU assay, and flow cytometry were conducted for detecting HCC cell multiplication, apoptosis, and cell cycle progression. The catRAPID database was adopted to predict the binding relationship between LINC00630 and E2F transcription factor 1 (E2F1), and RNA pull-down and RNA immunoprecipitation (RIP) assays were carried out to verify this binding relationship. The binding of E2F1 to the cyclin-dependent kinase 2 (CDK2) promoter region was verified by dual-luciferase reporter gene assay and chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR) assay. Western blotting was conducted to detect the protein expression of E2F1 and CDK2 in HCC cells. We report that LINC00630 expression was up-regulated in HCC and was significantly correlated with TNM stage and lymph node metastasis. LINC00630 overexpression facilitated HCC cell proliferation and cell cycle progression and inhibited the cell apoptosis, while LINC00630 knockdown had the opposite effects. LINC00630 directly bounds with E2F1. LINC00630 overexpression enhanced the binding of E2F1 to the CDK2 promoter region, thereby promoting CDK2 transcription, whereas knocking down LINC00630 inhibited CDK2 transcription. Collectively, LINC00630 promoted CDK2 transcription by recruiting E2F1 to the promoter region of CDK2, thereby promoting the malignant progression of HCC. Our data suggest that LINC00630 is a promising molecular target for HCC.

scholarly journals Bidirectional lncRNA Transfer between Cuscuta Parasites and Their Host Plant

2022 ◽  
Vol 23 (1) ◽  
pp. 561
Author(s):  
Yuguo Wu ◽  
Dong Luo ◽  
Longfa Fang ◽  
Qiang Zhou ◽  
Wenxian Liu ◽  
...  
Keyword(s):  
Host Plants ◽  
Target Genes ◽  
Chain Reaction ◽  
Non Coding Rna ◽  
Parasitic System ◽  
Polymerase Chain ◽  
Soybean Plants ◽  
Vascular Connections ◽  
Long Non Coding Rna ◽  
Material Exchange

Dodder species (Cuscuta spp.) are holoparasites that have extensive material exchange with their host plants through vascular connections. Recent studies on cross-species transfer have provided breakthrough insights, but little is known about the interaction mechanisms of the inter-plant mobile substances in parasitic systems. We sequenced the transcriptomes of dodder growing on soybean hosts to characterize the long non-coding RNA (lncRNA) transfer between the two species, and found that lncRNAs can move in high numbers (365 dodder lncRNAs and 14 soybean lncRNAs) in a bidirectional manner. Reverse transcription-polymerase chain reaction further confirmed that individual lncRNAs were trafficked in the dodder–soybean parasitic system. To reveal the potential functions of mobile transcripts, the Gene Ontology terms of mobile lncRNA target genes were predicted, and mobile dodder target genes were found to be mainly enriched in “metabolic process”, “catalytic activity”, “signaling”, and “response to stimulus” categories, whereas mobile soybean target genes were enriched in organelle-related categories, indicating that specific mobile lncRNAs may be important in regulating dodder parasitism. Our findings reveal that lncRNAs are transferred between dodder and its host soybean plants, which may act as critical regulators to coordinate the host–dodder interaction at the whole parasitic level.

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