The Role of p53-induced miR-145a in Senescence and Osteogenesis of Mesenchymal Stem Cells

Xia, Chao; Jiang, Tianyuan; Wang, Yonghui; Rothenberg, Marc E.; Hu, Yan; Gao, Yanhong

doi:10.21203/rs.3.rs-17497/v1

Cited by 4 publications

(3 citation statements)

References 42 publications

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“… 44 – 46 miR-145-5p seems to play an important role in the cell cycle and cell fate in mesenchymal stem cells as well. Preliminary work has shown that miR-145-5p and p53 work together to affect cell senescence in bone marrow, 47 and to affect the transition from stem cell to ASM under certain morphologic circumstances. 48 Indeed, miR-145-5p is involved in the transition of cells both to and from smooth muscle cells in other tissues.…”

Section: Discussionmentioning

confidence: 99%

COPD-associated miR-145-5p is downregulated in early-decline FEV1 trajectories in childhood asthma

Tiwari

Jiang

Kho

et al. 2021

Journal of Allergy and Clinical Immunology

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Background: Many microRNAs (miRNAs) have been associated with asthma and chronic obstructive pulmonary disease (COPD). Longitudinal lung function growth trajectories of children with asthma—normal growth, reduced growth (RG), early decline (ED), and RG with an ED (RGED)—have been observed, with RG and RGED associated with adverse outcomes, including COPD. Objective: Our aim was to determine whether circulating miRNAs from an early age in children with asthma would be prognostic of reduced lung function growth patterns over the next 16 years. Methods: We performed small RNA sequencing on sera from 492 children aged 5 to 12 years with mild-to-moderate asthma from the CAMP clinical trial, who were subsequently followed for 12 to 16 years. miRNAs were assessed for differential expression between previously assigned lung function growth patterns. Results: We had 448 samples and 259 miRNAs for differential analysis. In a comparison of the normal and the most severe group (ie, normal growth compared with RGED), we found 1 strongly dysregulated miRNA, hsa-miR-145-5p ( P < 8.01E–05). This miR was downregulated in both ED groups (ie, ED and RGED). We verified that miR-145-5p was strongly associated with airway smooth muscle cell growth in vitro . Conclusion: Our results showed that miR-145-5p is associated with the ED patterns of lung function growth leading to COPD in children with asthma and additionally increases airway smooth muscle cell proliferation. This represents a significant extension of our understanding of the role of miR-145-5p in COPD and suggests that reduced expression of miR-145-5p is a risk factor for ED of long-term lung function.

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Section: Discussionmentioning

confidence: 99%

COPD-associated miR-145-5p is downregulated in early-decline FEV1 trajectories in childhood asthma

Tiwari

Jiang

Kho

et al. 2021

Journal of Allergy and Clinical Immunology

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“…This manuscript has been released as a pre-print at (Chao Xia, et al) ( 52 ). We would like to thank Dr.…”

Section: Acknowledgmentsmentioning

confidence: 99%

The p53/miR-145a Axis Promotes Cellular Senescence and Inhibits Osteogenic Differentiation by Targeting Cbfb in Mesenchymal Stem Cells

et al. 2021

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The osteogenic differentiation capacity of senescent bone marrow mesenchymal stem cells (MSCs) is reduced. p53 not only regulates cellular senescence but also functions as a negative regulator in bone formation. However, the role of p53 in MSCs senescence and differentiation has not been extensively explored. In the present study, we investigated the molecular mechanism of p53 in MSCs senescence and osteogenic differentiation. We found that p53 was upregulated during cellular senescence and osteogenic differentiation of MSCs respectively induced by H2O2 and BMP9. Similarly, the expression of p53-induced miR-145a was increased significantly. Furthermore, Overexpression of miR-145a in MSCs promoted cellular senescence and inhibited osteogenic differentiation. Then, we identified that p53-induced miR-145a inhibited osteogenic differentiation by targeting core binding factor beta (Cbfb), and the restoration of Cbfb expression rescued the inhibitory effects of miRNA-145a. In summary, our results indicate that p53/miR-145a axis exert its functions both in promoting senescence and inhibiting osteogenesis of MSCs, and the novel p53/miR-145a/Cbfb axis in osteogenic differentiation of MSCs may represent new targets in the treatment of osteoporosis.

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“…This manuscript has been released as a pre-print at https:// www.researchsquare.com/article/rs-17497/v1 (Chao Xia, et al) (52). We would like to thank Dr.…”

Section: Data Availability Statementmentioning

confidence: 99%

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The Role of p53-induced miR-145a in Senescence and Osteogenesis of Mesenchymal Stem Cells

Cited by 4 publications

References 42 publications

COPD-associated miR-145-5p is downregulated in early-decline FEV1 trajectories in childhood asthma

COPD-associated miR-145-5p is downregulated in early-decline FEV1 trajectories in childhood asthma

The p53/miR-145a Axis Promotes Cellular Senescence and Inhibits Osteogenic Differentiation by Targeting Cbfb in Mesenchymal Stem Cells

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