MicroRNA let-7i-3p affects osteoblast differentiation in ankylosing spondylitis via targeting PDK1

Sun, Shiyuan; Xu, Ying; Zhu, Zhijun; Kong, Dequn; Liu, Hongming; Zhou, Zhao; Wang, Lei

doi:10.1080/15384101.2021.1930680

Cited by 3 publications

(1 citation statement)

References 37 publications

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“…In recent years, researchers have proposed aberrant expression of miRNAs in AS serves role in regulating osteoblast differentiation ( 17 , 18 ). For example, miR-124 increases osteoblast differentiation of AS fibroblasts via glycogen synthase kinase-3β-mediated Wnt/β-catenin pathway signaling ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

miR‑150‑5p inhibits osteogenic differentiation of fibroblasts in ankylosing spondylitis by targeting VDR

Shi

2022

Exp Ther Med

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Dysregulated microRNAs (miRNAs or miRs) serve potential roles in inflammatory systemic disease, including ankylosing spondylitis (AS). The aim of the present study was to investigate the potential function of miR-150-5p in osteogenic differentiation of AS fibroblasts and its underlying mechanism. The expression of miR-150-5p and vitamin D receptor (VDR) in AS joint capsules and fibroblasts was detected by reverse transcription-quantitative (RT-q)PCR and western blotting. Following overexpression of miR-150-5p, the alteration in osteogenic gene expression was detected by RT-qPCR, western blotting and alkaline phosphatase activity assay, as well as alizarin red staining. The association between miR-150-5p and VDR was confirmed by luciferase assay and rescue experiments were performed. Patients with AS exhibited decreased expression of miR-150-5p in joint capsules. Treatment with bone morphogenic protein 2 (BMP-2) and transforming growth factor-β1 (TGF-β1) led to downregulation of miR-150-5p in AS fibroblasts. Enforced expression of miR-150-5p attenuated osteogenic differentiation of AS fibroblasts. These results demonstrated that miR-150-5p inhibited osteogenic differentiation of AS fibroblasts by targeting VDR. miR-150-5p overexpression decreased osteogenic transformation of fibroblasts by decreasing VDR expression in AS.

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Section: Discussionmentioning

confidence: 99%

miR‑150‑5p inhibits osteogenic differentiation of fibroblasts in ankylosing spondylitis by targeting VDR

Shi

2022

Exp Ther Med

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Let-7i-3p inhibits the cell cycle, proliferation, invasion, and migration of colorectal cancer cells via downregulating CCND1

Chen

et al. 2022

Open Medicine

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Dysregulated microRNAs are closely related to the malignant progression of colorectal cancer (CRC). Although abnormal let-7i-3p expression has been reported in various human cancers, its biological role and potential mechanism in CRC remain unclear. Therefore, the purpose of this study was to investigate the expression and regulation of let-7i-3p in CRC. Here, we demonstrated that let-7i-3p expression was significantly downregulated in three CRC cell lines while CyclinD1 (CCND1) was upregulated compared with the normal colon epithelial FHC cells. Moreover, bioinformatics and luciferase reporter assays revealed that CCND1 was a direct functional target of let-7i-3p. In addition, let-7i-3p overexpression or CCND1 silencing inhibited cell cycle, proliferation, invasion, and migration and diminished the activation of p-ERK in HCT116 cells. However, exogenously expressing CCND1 alleviated these effects. Taken together, our findings may provide new insight into the pathogenesis of CRC and let-7i-3p/CCND1 might function as new therapeutic targets for CRC.

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Pdk3’s role in RANKL-induced osteoclast differentiation: insights from a bone marrow macrophage model

Zhang,

Wang,

2024

PeerJ

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Background Osteoporosis (OP) is a chronic disease characterized by decreased bone mass, loss of skeletal structural integrity and increased susceptibility to fracture. Available studies have shown that the pyruvate dehydrogenase kinase (PDK) family is associated with osteoclastogenesis and bone loss, but the specific role of Pdk3 in bone pathology has not been systematically investigated. Methods A cell OP model was established in receptor activator for nuclear factor-κB Ligand (RANKL)-induced bone marrow macrophages (BMMs). Hereafter, the expression levels of Pdk3 and osteoclastogenesis feature genes including nuclear factor of activated T cells 1 (Nfatc1), Cathepsin K (Ctsk), osteoclast associated Ig-like receptor (Oscar) in BMMs-derived osteoclasts were examined based on real-time quantitative PCR and western blotting methods. Further, the phosphorylation of ERK, P65 and JAK/STAT and their correlation was Pdk3 was gauged. In particular, changes in the activity of these signaling pathways were observed by silencing experiments of the Pdk3 gene (using small interfering RNA). Finally, the effects of Pdk3 gene silencing on signaling pathway activity, osteoclastogenesis, and related inflammatory and apoptotic indicators were observed by transfection with PDK3-specific siRNA. Results Following RANKL exposure, the levels of Pdk3 and osteoclastogenesis feature genes were all elevated, and a positive correlation between Pdk3 and osteoclastogenesis feature genes was seen. Meanwhile, ERK, P65 and JAK/STAT phosphorylation was increased by RANKL, and Pdk3 was confirmed to be positively correlated with the phosphorylation of ERK, P65 and JAK/STAT. Additionally, in RANKL-exposed osteoclasts, Pdk3 knockdown diminished the phosphorylation of ERK, P65 and JAK/STAT, reduced the expressions of osteoclastogenesis feature genes. Importantly, knockdown of Pdk3 also reduced the expression of inflammatory cytokines and resulted in elevated levels of Bax and Casp3 expression, as well as downregulation of Bcl2 expression. Conclusion This study reveals for the first time the role of Pdk3 in RANKL-induced osteoclastogenesis and OP. These findings provide a foundation for future studies on the role of Pdk3 in other bone diseases and provide new ideas for the development of OP therapeutics targeting Pdk3.

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MicroRNA let-7i-3p affects osteoblast differentiation in ankylosing spondylitis via targeting PDK1

Cited by 3 publications

References 37 publications

miR‑150‑5p inhibits osteogenic differentiation of fibroblasts in ankylosing spondylitis by targeting VDR

miR‑150‑5p inhibits osteogenic differentiation of fibroblasts in ankylosing spondylitis by targeting VDR

Let-7i-3p inhibits the cell cycle, proliferation, invasion, and migration of colorectal cancer cells via downregulating CCND1

Pdk3’s role in RANKL-induced osteoclast differentiation: insights from a bone marrow macrophage model

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