miR-122 Exerts Inhibitory Effects on Osteoblast Proliferation/Differentiation in Osteoporosis by Activating the PCP4-Mediated JNK Pathway

Meng, Yichen; Lin, Tao; Jiang, Heng; Zheng, Zhaohui; Shu, Lun; Yin, Jing; Ma, Xuelei; Gao, Rui; Zhou, Xuhui

doi:10.1016/j.omtn.2019.11.038

Cited by 33 publications

(25 citation statements)

References 35 publications

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“…A number of studies have demonstrated that miRNAs exhibit roles in numerous biological processes by regulating their mRNA targets, including in cell development, tumorigenesis, cell differentiation and aging (17)(18)(19). In OS, the miRNA expression profile has been extensively studied, and a variety of miRNAs has been identified to play a role in OS, such as miR-422a, miR-145 and miR-194 (20).…”

Section: Introductionmentioning

confidence: 99%

Long non‑coding RNA NR2F1‑AS1 facilitates the osteosarcoma cell malignant phenotype via the miR‑485‑5p/miR‑218‑5p/BIRC5 axis

Jia

Wang

et al. 2020

Oncol Rep

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Long non-coding RNA (lncRNA) NR2F1 antisense RNA 1 (NR2F1-AS1) has been reported to be an oncogene in several cancer types, including osteosarcoma (OS). However, the underlying fundamental molecular mechanism of NR2F1-AS1 in OS remains largely unknown, which the present study aimed to elucidate. The present study demonstrated that NR2F1-AS1 expression is markedly increased in OS, and NR2F1-AS1 was shown to exert oncogenic functions in OS. Further molecular mechanistic studies revealed that microRNA (miR)-485-5p and miR-218-5p were direct targets of NR2F1-AS1. More importantly, miR-485-5p and miR-218-5p exhibited low expression levels and were negatively correlated with NR2F1-AS1 expression in OS tissues. It was then identified that baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) was a direct target of miR-485-5p and miR-218-5p in OS cells. Furthermore, a series of experiments suggested that NR2F1-AS1 affects the proliferation, migration, invasion and apoptosis of OS cells by regulating BIRC5. Finally, it was revealed that silencing of NR2F1-AS1 repressed the OS cell malignant phenotype by binding with miR-485-5p and miR-218-5p, and then downregulating BIRC5 expression, which suggests that the NR2F1-AS1/miR-485-5p/miR-218-5p/BIRC5 axis could be a potential target for treating OS.

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Section: Introductionmentioning

confidence: 99%

Long non‑coding RNA NR2F1‑AS1 facilitates the osteosarcoma cell malignant phenotype via the miR‑485‑5p/miR‑218‑5p/BIRC5 axis

Jia

Wang

et al. 2020

Oncol Rep

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“…The signi cance of c-Jun N-terminal kinase (JNK) has been validated in cell cycle regulation, apoptosis and cellular stress, and it has been also highlighted to participate in osteogenic differentiation of mesenchymal stem cells [11]. More speci cally, miR-122 elicited inhibitory effects on osteoblast proliferation through the JNK pathway [12]. The present study hypothesized that miR-497-5p may enhance the osteoblast differentiation by regulating HMGA2 and the JNK signaling pathway.…”

Section: Introductionmentioning

confidence: 81%

“…Our study also showed that miR-497-5p impaired the JNK signaling potentiation by lowering the extents of JNK phosphorylation, which was also reversed by HMGA2 upregulation. Recently, the JNK signaling pathway inhibitor was revealed to enhance the osteoblast differentiation that hampered by miR-122 mimic [12]. Pre-treatment with MAPK inhibitors reduced the protein expression of Bax promoted by IL-1α in the MC3T3-E1 cells, suggesting that the signi cance of JNK and the p38 MAPK signaling in modulating IL-1α-induced apoptosis and osteoblast differentiation of MC3T3-E1 cells [23].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-497-5p stimulates osteoblast differentiation through HMGA2-mediated JNK signaling pathway

Zhao

Yang

Wang

et al. 2020

Preprint

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Background: Osteoporosis (OP) has the characteristics of the decline in bone mineral density and worsening of bone quality, contributing to higher risk of fractures. Some microRNAs (miRNAs) have been validated as possible mediators of osteoblast differentiation. We herein aimed to clarify whether miR-497-5p regulates differentiation of osteoblasts in MC3T3-E1 cells.Methods: The expression of miR-497-5p in OP patients and controls was measured by RT-qPCR, and its expression changes during osteoblast differentiation were determined as well. The effects of miR-497-5p on differentiation of MC3T3-E1 cells were studied using MTT, ALR staining and ARS staining. The target gene of miR-497-5p was predicted by TargetScan, and the effects of its target gene on differentiation and the pathway involved were investigated.Results: miR-497-5p expression expressed poorly in OP patients and its expression was upregulated during MC3T3-E1 cell differentiation. Overexpression of miR-497-5p promoted mineralized nodule formation and the expression of RUNX2 and OCN. miR-497-5p targeted high mobility group AT-Hook 2 (HMGA2), while upregulation of HMGA2 inhibited osteogenesis induced by miR-497-5p mimic. miR-497-5p significantly impaired the c-Jun NH2-terminal kinase (JNK) pathway, whereas HMGA2 activated this pathway. Activation of the JNK pathway inhibited the stimulative role of miR-497-5p mimic in osteogenesis.Conclusions: miR-497-5p inhibits development of OP by hampering osteogenesis via targeting HMGA2. We hence conclude that targeting miR-497-5p might be an attractive therapeutic option for OP.

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“…Our study also showed that miR-497-5p impaired the JNK signaling potentiation by lowering the extents of JNK phosphorylation, which was also reversed by HMGA2 upregulation. Recently, the JNK signaling pathway inhibitor was revealed to enhance osteoblast differentiation [ 17 ]. Pre-treatment with MAPK inhibitors reduced the protein expression of Bax promoted by IL-1α in the MC3T3-E1 cells, suggesting the significance of JNK and the p38 MAPK signaling in modulating IL-1α-induced apoptosis and osteoblast differentiation of MC3T3-E1 cells [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…The significance of c-Jun N-terminal kinase (JNK) has been validated in cell cycle regulation, apoptosis, and cellular stress, and it has been also highlighted to participate in osteogenic differentiation of mesenchymal stem cells [ 16 ]. More specifically, miR-122 elicited inhibitory effects on osteoblast proliferation through the JNK pathway [ 17 ]. The present study hypothesized that miR-497-5p enhances the osteoblast differentiation by regulating HMGA2 and the JNK signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-497-5p stimulates osteoblast differentiation through HMGA2-mediated JNK signaling pathway

et al. 2020

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Background Osteoporosis (OP) has the characteristics of the decline in bone mineral density and worsening of bone quality, contributing to a higher risk of fractures. Some microRNAs (miRNAs) have been validated as possible mediators of osteoblast differentiation. We herein aimed to clarify whether miR-497-5p regulates the differentiation of osteoblasts in MC3T3-E1 cells. Methods The expression of miR-497-5p in OP patients and controls was measured by RT-qPCR, and its expression changes during osteoblast differentiation were determined as well. The effects of miR-497-5p on the differentiation of MC3T3-E1 cells were studied using MTT, ALR staining, and ARS staining. The target gene of miR-497-5p was predicted by TargetScan, and the effects of its target gene on differentiation and the pathway involved were investigated. Results miR-497-5p expressed poorly in OP patients, and its expression was upregulated during MC3T3-E1 cell differentiation. Overexpression of miR-497-5p promoted mineralized nodule formation and the expression of RUNX2 and OCN. miR-497-5p targeted high mobility group AT-Hook 2 (HMGA2), while the upregulation of HMGA2 inhibited osteogenesis induced by miR-497-5p mimic. miR-497-5p significantly impaired the c-Jun NH2-terminal kinase (JNK) pathway, whereas HMGA2 activated this pathway. Activation of the JNK pathway inhibited the stimulative role of miR-497-5p mimic in osteogenesis. Conclusions miR-497-5p inhibits the development of OP by promoting osteogenesis via targeting HMGA2.

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miR-122 Exerts Inhibitory Effects on Osteoblast Proliferation/Differentiation in Osteoporosis by Activating the PCP4-Mediated JNK Pathway

Cited by 33 publications

References 35 publications

Long non‑coding RNA NR2F1‑AS1 facilitates the osteosarcoma cell malignant phenotype via the miR‑485‑5p/miR‑218‑5p/BIRC5 axis

Long non‑coding RNA NR2F1‑AS1 facilitates the osteosarcoma cell malignant phenotype via the miR‑485‑5p/miR‑218‑5p/BIRC5 axis

MicroRNA-497-5p stimulates osteoblast differentiation through HMGA2-mediated JNK signaling pathway

MicroRNA-497-5p stimulates osteoblast differentiation through HMGA2-mediated JNK signaling pathway

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