LncRNA H19 mediates BMP9-induced angiogenesis in mesenchymal stem cells by promoting the p53-Notch1 angiogenic signaling axis

Du, Chengcheng; Cheng, Qiang; Zhao, Piao; Wang, Claire; Zhu, Zhenglin; Wu, Xiangdong; Gao, Shengqiang; Chen, Bowen; Zou, Jing; Huang, Wei; Liao, Junyi

doi:10.1016/j.gendis.2022.04.013

Cited by 5 publications

(3 citation statements)

References 68 publications

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“…Specifically, in accordance with our findings, we have shown that overexpression of lncH19 enhanced TP53 expression, whereas H19 silencing exerted the opposite effect (Zhuang et al, 2021). In addition, Du et al have found that lncH19 promotes p53 phosphorylation by a direct interaction, an effect that results in increased NOTCH-mediated angiogenesis in mesenchymal stem cells (Du et al, 2023).…”

Section: Discussionsupporting

confidence: 92%

Long non-coding RNA H19 enhances the pro-apoptotic activity of ITF2357 (a histone deacetylase inhibitor) in colorectal cancer cells

Zichittella,

Loria,

Celesia

et al. 2023

Front. Pharmacol.

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Introduction: Long non-coding RNA H19 (lncH19) is highly expressed in colorectal cancer (CRC) and plays critical roles in tumor development, proliferation, metastasis, and drug resistance. Indeed, the expression of lncH19 usually affects the outcomes of chemo-, endocrine, and targeted therapies. ITF2357 (givinostat) is a histone deacetylase inhibitor (HDACi) that revealed a significant anti-tumor action by inducing apoptosis in different tumor models, including leukemia, melanoma, and glioblastoma. However, no data are present in the literature regarding the use of this compound for CRC treatment. Here, we investigate the role of lncH19 in ITF2357-induced apoptosis in CRC cells.Methods: The HCT-116 CRC cell line was stably silenced for H19 to investigate the role of this lncRNA in ITF2357-induced cell death. Cell viability assays and flow cytometric analyses were performed to assess the anti-proliferative and pro-apoptotic effects of ITF2357 in CRC cell lines that are silenced or not for lncH19. RT-PCR and Western blot were used to study the effects of ITF2357 on autophagy and apoptosis markers. Finally, bioinformatics analyses were used to identify miRNAs targeting pro-apoptotic factors that can be sponged by lncH19.Results: ITF2357 increased the expression levels of H19 and reduced HCT-116 cell viability, inducing apoptosis, as demonstrated by the increase in annexin-V positivity, caspase 3 cleavage, and poly (ADP-ribose) polymerase (PARP-1) degradation. Interestingly, the apoptotic effect of ITF2357 was much less evident in lncH19-silenced cells. We showed that lncH19 plays a functional role in the pro-apoptotic activity of the drug by stabilizing TP53 and its transcriptional targets, NOXA and PUMA. ITF2357 also induced autophagy in CRC cells, which was interpreted as a pro-survival response not correlated with lncH19 expression. Furthermore, ITF2357 induced apoptosis in 5-fluorouracil-resistant HCT-116 cells that express high levels of lncH19.Conclusion: This study shows that lncH19 expression contributes to ITF2357-induced apoptosis by stabilizing TP53. Overall, we suggest that lncH19 expression may be exploited to favor HDACi-induced cell death and overcome 5-fluorouracil chemoresistance.

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Section: Discussionsupporting

confidence: 92%

Long non-coding RNA H19 enhances the pro-apoptotic activity of ITF2357 (a histone deacetylase inhibitor) in colorectal cancer cells

Zichittella,

Loria,

Celesia

et al. 2023

Front. Pharmacol.

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“…MSCs have the potential for vascular epithelial differentiation, and MSC-exosomes can promote in situ vascular epithelial cell differentiation and repair vascular damage. MSCs can mediate BMP9 to induce angiogenesis by fostering the p53-Notch1 angiogenesis signaling axis via LncRNA-H19 [ 53 ]. Through the promotion of 17β-estradiol, MSCs express CD31, Akt, and p-Akt proteins, triggering signaling pathways such as MAPK and PI3K-Akt to achieve angiogenesis [ 54 ].…”

Section: Promote Angiogenesis and Improve Microcirculation To Achieve...mentioning

confidence: 99%

Perspectives on Osteoarthritis Treatment with Mesenchymal Stem Cells and Radix Achyranthis Bidentatae

2023

Aging dis

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Knee osteoarthritis, a widespread degenerative condition, impacts a younger population and leads to high disability rates. Nature often provides solutions for aging and disease prevention. Mesenchymal stem cells (MSCs) and Radix Achyranthis Bidentatae (AB) are natural substances with potential. MSCs can transform into various tissues, alleviating symptoms by releasing factors and miRNA, potentially slowing osteoarthritis progression. AB's compositions target knee joint cells, enhancing internal conditions and joint function. Both MSCs and AB share mechanisms for immune regulation, reducing cartilage apoptosis, promoting chondrocyte formation, and addressing osteoporosis. They also influence estrogen and gut flora. This article reviews their roles in treating osteoarthritis, discussing apoptosis reduction, chondrocyte growth, bone enhancement, angiogenesis, and regulation of estrogen and intestinal flora. It explores their relationship and suggests AB's potential in stimulating mesenchymal stem cell repair for knee osteoarthritis treatment.

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“…Besides, PD‐1 involves in the inhibition of SCAPs differentiation by targeting SHP2 (Li, Li, et al., 2022). Research has shown that multiple receptor molecules, transcription factors and noncoding RNAs interact to form a complex and fine regulatory network of stem cells (Chen & Zhang, 2023; Du et al., 2022; Fan et al., 2021). Therefore, further elucidating the intracellular molecular mechanisms through which the biological characteristics of SCAPs are regulated and finding safe, effective and controllable potential targets are central issues in realizing the clinical application of SCAPs.…”

Section: Introductionmentioning

confidence: 99%

Circ‐ZNF236 mediates stem cells from apical papilla differentiation by regulating LGR4‐induced autophagy

Xiao,

Chen,

et al. 2024

Int Endodontic J

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AimHuman stem cells from the apical papilla (SCAPs) are an appealing stem cell source for tissue regeneration engineering. Circular RNAs (circRNAs) are known to exert pivotal regulatory functions in various cell differentiation processes, including osteogenesis of mesenchymal stem cells. However, few studies have shown the potential mechanism of circRNAs in the odonto/osteogenic differentiation of SCAPs. Herein, we identified a novel circRNA, circ‐ZNF236 (hsa_circ_0000857) and found that it was remarkably upregulated during the SCAPs committed differentiation. Thus, in this study, we showed the significance of circ‐ZNF236 in the odonto/osteogenic differentiation of SCAPs and its underlying regulatory mechanisms.MethodologyThe circular structure of circ‐ZNF236 was identified via Sanger sequencing, amplification of convergent and divergent primers. The proliferation of SCAPs was detected by CCK‐8, flow cytometry analysis and EdU incorporation assay. Western blotting, qRT‐PCR, Alkaline phosphatase (ALP) and Alizarin red staining (ARS) were performed to explore the regulatory effect of circ‐ZNF236/miR‐218‐5p/LGR4 axis in the odonto/osteogenic differentiation of SCAPs in vitro. Fluorescence in situ hybridization, as well as dual‐luciferase reporting assays, revealed that circ‐ZNF236 binds to miR‐218‐5p. Transmission electron microscopy (TEM) and mRFP‐GFP‐LC3 lentivirus were performed to detect the activation of autophagy.ResultsCirc‐ZNF236 was identified as a highly stable circRNA with a covalent closed loop structure. Circ‐ZNF236 had no detectable influence on cell proliferation but positively regulated SCAPs odonto/osteogenic differentiation. Furthermore, circ‐ZNF236 was confirmed as a sponge of miR‐218‐5p in SCAPs, while miR‐218‐5p targets LGR4 mRNA at its 3′‐UTR. Subsequent rescue experiments revealed that circ‐ZNF236 regulates odonto/osteogenic differentiation by miR‐218‐5p/LGR4 in SCAPs. Importantly, circ‐ZNF236 activated autophagy, and the activation of autophagy strengthened the committed differentiation capability of SCAPs. Subsequently, in vivo experiments showed that SCAPs overexpressing circ‐ZNF236 promoted bone formation in a rat skull defect model.ConclusionsCirc‐ZNF236 could activate autophagy through increasing LGR4 expression, thus positively regulating SCAPs odonto/osteogenic differentiation. Our findings suggested that circ‐ZNF236 might represent a novel therapeutic target to prompt the odonto/osteogenic differentiation of SCAPs.

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LncRNA H19 mediates BMP9-induced angiogenesis in mesenchymal stem cells by promoting the p53-Notch1 angiogenic signaling axis

Cited by 5 publications

References 68 publications

Long non-coding RNA H19 enhances the pro-apoptotic activity of ITF2357 (a histone deacetylase inhibitor) in colorectal cancer cells

Long non-coding RNA H19 enhances the pro-apoptotic activity of ITF2357 (a histone deacetylase inhibitor) in colorectal cancer cells

Perspectives on Osteoarthritis Treatment with Mesenchymal Stem Cells and Radix Achyranthis Bidentatae

Circ‐ZNF236 mediates stem cells from apical papilla differentiation by regulating LGR4‐induced autophagy

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