An emerging potential therapeutic target for osteoporosis: LncRNA H19/miR-29a-3p axis

Li, Ziqi; Hong, Zhinan; Zheng, Yuesheng; Dong, Yuhan; He, Wei; Yuan, Ying-Jia; Guo, Junbiao

doi:10.4081/ejh.2020.3155

Cited by 13 publications

(5 citation statements)

References 21 publications

(16 reference statements)

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“…It is also a direct target of TF HIF1α, and its expression can be inhibited by miRNA MIR29a [ 130 , 131 ]. Thirdly, TF FOXA1 has been found to bind to E1 enhancer of gene H19 and correlates with lncRNA gene H19 activation [ 132 ]; lncRNA H19 has been shown to suppress miRNA MIR29a [ 133 ]. Remarkably, in an ARDS mouse model induced by LPS, both expressions of FOXA1 and H19 were upregulated.…”

Section: Resultsmentioning

confidence: 99%

Repurposing Multiple-Molecule Drugs for COVID-19-Associated Acute Respiratory Distress Syndrome and Non-Viral Acute Respiratory Distress Syndrome via a Systems Biology Approach and a DNN-DTI Model Based on Five Drug Design Specifications

Ting

Chen

2022

IJMS

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The coronavirus disease 2019 (COVID-19) epidemic is currently raging around the world at a rapid speed. Among COVID-19 patients, SARS-CoV-2-associated acute respiratory distress syndrome (ARDS) is the main contribution to the high ratio of morbidity and mortality. However, clinical manifestations between SARS-CoV-2-associated ARDS and non-SARS-CoV-2-associated ARDS are quite common, and their therapeutic treatments are limited because the intricated pathophysiology having been not fully understood. In this study, to investigate the pathogenic mechanism of SARS-CoV-2-associated ARDS and non-SARS-CoV-2-associated ARDS, first, we constructed a candidate host-pathogen interspecies genome-wide genetic and epigenetic network (HPI-GWGEN) via database mining. With the help of host-pathogen RNA sequencing (RNA-Seq) data, real HPI-GWGEN of COVID-19-associated ARDS and non-viral ARDS were obtained by system modeling, system identification, and Akaike information criterion (AIC) model order selection method to delete the false positives in candidate HPI-GWGEN. For the convenience of mitigation, the principal network projection (PNP) approach is utilized to extract core HPI-GWGEN, and then the corresponding core signaling pathways of COVID-19-associated ARDS and non-viral ARDS are annotated via their core HPI-GWGEN by KEGG pathways. In order to design multiple-molecule drugs of COVID-19-associated ARDS and non-viral ARDS, we identified essential biomarkers as drug targets of pathogenesis by comparing the core signal pathways between COVID-19-associated ARDS and non-viral ARDS. The deep neural network of the drug–target interaction (DNN-DTI) model could be trained by drug–target interaction databases in advance to predict candidate drugs for the identified biomarkers. We further narrowed down these predicted drug candidates to repurpose potential multiple-molecule drugs by the filters of drug design specifications, including regulation ability, sensitivity, excretion, toxicity, and drug-likeness. Taken together, we not only enlighten the etiologic mechanisms under COVID-19-associated ARDS and non-viral ARDS but also provide novel therapeutic options for COVID-19-associated ARDS and non-viral ARDS.

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Section: Resultsmentioning

confidence: 99%

Repurposing Multiple-Molecule Drugs for COVID-19-Associated Acute Respiratory Distress Syndrome and Non-Viral Acute Respiratory Distress Syndrome via a Systems Biology Approach and a DNN-DTI Model Based on Five Drug Design Specifications

Ting

Chen

2022

IJMS

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“…Furthermore, some contrasting results were reported for the H19 expression in postmenopausal osteoporosis patients. In Xiaoling et al’s research, a significant decrease in H19 was shown [ 59 ], whereas Li et al found significantly a higher expression in this group [ 60 ]. We did not obtain a different H19 expression in patients who suffered from osteoporosis.…”

Section: Discussionmentioning

confidence: 98%

Is H19 RNA a Useful Marker of Acromegaly and Its Complications? A Preliminary Study

Rolla

Jawiarczyk-Przybyłowska

Kolačkov

et al. 2023

Biomedicines

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Acromegaly is a rare endocrine disorder caused by somatotroph pituitary adenoma. Besides its typical symptoms, it contributes to the development of cardiovascular, metabolic, and bone comorbidities. H19 RNA is a long non-coding RNA and it is suspected to be involved in tumorigenesis, cancer progression, and metastasis. H19 RNA is a novel biomarker for the diagnosis and monitoring of neoplasms. Moreover, there might be an association between H19 and cardiovascular and metabolic diseases. We enrolled 32 acromegaly patients and 25 controls. We investigated whether whole blood H19 RNA expression is associated with the diagnosis of acromegaly. Correlations between H19 and tumour dimension, invasiveness, and biochemical and hormonal parameters were evaluated. We analysed the coincidence of acromegaly comorbidities with H19 RNA expression. In the results, we did not observe a statistically significant difference in H19 RNA expression between acromegaly patients and the controls. There were no correlations between H19 and the adenoma size and infiltration and patients’ biochemical and hormonal statuses. In the acromegaly group, hypertension, goitre, and cholelithiasis were observed more frequently. The diagnosis of acromegaly was a factor contributing to the occurrence of dyslipidaemia, goitre, and cholelithiasis. We found an association between H19 and cholelithiasis in acromegaly patients. To conclude, H19 RNA expression is not a relevant marker for diagnosis and monitoring of acromegaly patients. There is a higher risk of hypertension, goitre, and cholelithiasis related to acromegaly. Cholelithiasis is associated with a higher H19 RNA expression.

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“…MiRNA also exerts a significant effect on the regulation of bone inflammation. For example, Li et al ( Li Z et al, 2020 ) pointed out that miR-29a-3p regulates the inflammatory response of osteoclast to affect the occurrence of osteoporosis. The results of our study demonstrated that miR-27a-3p can act as a suppressor of bone formation and destroy the balance of inflammation in bone tissue.…”

Section: Discussionmentioning

confidence: 99%

MiR-27a-3p Targets GLP1R to Regulate Differentiation, Autophagy, and Release of Inflammatory Factors in Pre-Osteoblasts via the AMPK Signaling Pathway

et al. 2022

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Objective: Osteoporosis is caused by the dysregulation of bone homeostasis which is synergistically mediated by osteoclasts and osteoblasts. MiR-27a-3p is a key inhibitor of bone formation. Hence, unearthing the downstream target gene of miR-27a-3p is of great significance to understand the molecular mechanism of osteoporosis.Methods: Bioinformatics analysis was utilized to find the downstream target gene of miR-27a-3p, and dual-luciferase reporter assay was conducted to validate the interplay of miR-27a-3p and GLP1R. Besides, qRT-PCR, Western blot, and enzyme-linked immunosorbent assay (ELISA) were employed to verify the impact of miR-27a-3p on GLP1R expression and the differentiation, autophagy, and inflammatory response of MC3T3-E1 pre-osteoblasts.Results: Dual-luciferase assay validated that miR-27a-3p directly targeted GLP1R. Additionally, posttreatment of MC3T3-E1 cells with miR-27a-3p mimics resulted in a remarkable decrease in expression levels of GLP1R, cell differentiation marker gene, autophagy marker gene, and AMPK. These results indicated that miR-27a-3p targeted GLP1R to inhibit AMPK signal activation and pre-osteoblast differentiation and autophagy, while promoting the release of inflammatory factors.Conclusion: The miR-27a-3p/GLP1R regulatory axis in pre-osteoblasts contributes to understanding the molecular mechanism of osteoporosis.

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An emerging potential therapeutic target for osteoporosis: LncRNA H19/miR-29a-3p axis

Cited by 13 publications

References 21 publications

Repurposing Multiple-Molecule Drugs for COVID-19-Associated Acute Respiratory Distress Syndrome and Non-Viral Acute Respiratory Distress Syndrome via a Systems Biology Approach and a DNN-DTI Model Based on Five Drug Design Specifications

Repurposing Multiple-Molecule Drugs for COVID-19-Associated Acute Respiratory Distress Syndrome and Non-Viral Acute Respiratory Distress Syndrome via a Systems Biology Approach and a DNN-DTI Model Based on Five Drug Design Specifications

Is H19 RNA a Useful Marker of Acromegaly and Its Complications? A Preliminary Study

MiR-27a-3p Targets GLP1R to Regulate Differentiation, Autophagy, and Release of Inflammatory Factors in Pre-Osteoblasts via the AMPK Signaling Pathway

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