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Cell Oncol (Dordr) ; 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31884576


PURPOSE: The etiology of nasopharyngeal carcinoma (NPC) is multifactorial, complex and not fully characterized yet. MicroRNAs (miRNAs or miRs) have been found to contribute to the development and progression of NPC. Here, we aimed to investigate the putative role of miR-129-5p in NPC lymphangiogenesis and lymph node metastasis (LNM), including the involvement of its target gene ZIC2 and the Hedgehog signaling pathway. METHODS: The expression of miR-129-5p and ZIC2 in primary NPC tissues was assessed using RT-qPCR and Western blot analyses, followed by LNM and lymph vessel density (LVD) correlation analyses. A direct interaction between miR-129-5p and ZIC2 was verified using a dual-luciferase reporter assay. Gain- and loss-of-function experiments were conducted to investigate the effects of miR-129-5p and ZIC2 expression on NPC cell invasion, migration and proliferation in vitro, as well as on LDV and LNM in nude mice in vivo. Additionally, RT-qPCR and Western blot analyses were performed to determine the expression levels of Hedgehog signaling pathway-related factors. RESULTS: We found that ZIC2 was highly expressed, and miR-129-5p was lowly expressed, in primary NPC tissues. In addition, we found that miR-129-5p can directly bind to and reduce ZIC2 expression. LVD was found to be negatively correlated with miR-129-5p and to be positively correlated with ZIC2 expression. Concomitantly, we found that miR-129-5p abrogated activation of the Hedgehog signaling pathway via ZIC2 targeting, leading to suppression of NPC cell invasion, migration and proliferation in vitro as well as suppression of LNM and LVD in vivo. CONCLUSIONS: From our data we conclude that miR-129-5p, by decreasing ZIC2 expression, may inhibit NPC lymphangiogenesis and LNM through suppression of the Hedgehog signaling pathway.

J Cell Physiol ; 234(2): 1442-1451, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30132853


Human dental pulp stem cells (hDPSCs) are primarily derived from the pulp tissues of permanent third molar teeth. They were widely used in human bone tissue engineering. It was previously indicated that microRNA (miR) expressions are closely associated with hDPSCs development. However, the specific effect of miR-488 on hDPSCs still remains unclear. In this study, we aimed to investigate effects of miR-488 on the differentiation of hDPSCs into odontoblast cells through the p38 mitogen-activated protein kinases (MAPK) signaling pathway by binding to MAPK1. The hDPSCs were isolated and cultured in vitro. Dual-luciferase reporter gene assay was performed to test the relationship between MAPK1 (p38) and miR-488. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to detect the mRNA and protein expressions of p38 MAPK signaling pathway-related genes (MAPK1, Ras, and Mitogen-activated protein kinase kinase 3/6 [MKK3/6]), along with expressions of dentin Sialophosphoprotein (DSPP), alkaline phosphatase (ALP), and osteonectin (OCN). ALP staining and alizarin red staining were conducted to detect ALP activity and degree of mineralization. Initially, we found that MAPK1 was the target gene of miR-488. Besides, downregulation of miR-488 was observed to stimulate the p38 MAPK signaling pathway and to increase the messenger RNA and protein expressions of DSPP, ALP, and OCN. Furthermore, ALP activity and formation of a mineralized nodule in hDPSCs were enhanced upon downregulation of miR-488. The aforementioned findings provided evidence supporting that downregulation of miR-488 promotes odontoblastic differentiation of hDPSCs through the p38 MAPK signaling pathway by targeting MAPK1, paving the basis for further study about hDPSCs.

Diferenciação Celular , Polpa Dentária/enzimologia , MicroRNAs/metabolismo , Odontoblastos/enzimologia , Células-Tronco/enzimologia , Calcificação de Dente , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Polpa Dentária/citologia , Regulação para Baixo , Ativação Enzimática , Células HEK293 , Humanos , MicroRNAs/genética , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Transdução de Sinais
Zhonghua Kou Qiang Yi Xue Za Zhi ; 43(1): 21-5, 2008 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-18380969


OBJECTIVE: To investigate the effect of systematic administration of simvastatin on the bone morphogenetic protein-2 (BMP-2) expression in the periodontal tissue after rat tooth movement and on the relapse of tooth movement. METHODS: Orthodontic tooth movement of upper first molar was performed in 32 rats with coil spring for 21 days. The 32 rats were randomly allocated into 4 groups: negative control group (isotonic saline) and three experimental groups (2.5 mg x kg(-1), 5.0 mg x kg(-1) and 10.0 mg x kg(-1)). The simvastatin started to be administered to the experimental groups 1 day before appliances were removed, and once a day there after for 4 weeks. The negative control group received the isotonic saline only. The interdental distance between the first and second maxillary molars were measured, when appliances were removed, and 1 week and 4 weeks after that. After the rats were sacrificed, sections of first maxillary molar and periodontal tissue were studied by immunohistochemistry. RESULTS: The number and percentage of relapse was lower in the three experimental groups than in the negative control group (P < 0.05, P < 0.01). The lower dose was given, the less relapse there was, with the lowerest dose resulting in lowest percentage of relapse (26.81% and 53.38%). BMP-2 expression in experimental groups was higher than in the negative control group, with the lowerest dose group showing the highest expression (P < 0.001). The BMP-2 expression on the tension side was slightly stronger than that on the compression side (P > 0.05). CONCLUSIONS: Systemic administration of simvastatin could decrease the extent of relapse of the orthodontic-moved tooth in rat, and the lower-dose of simvastatin seemed more effective. The possible mechanism for this may be that simvastatin functions by increasing the expression of BMP-2 in the periodontal tissue, accelerating the osteoblast activity and promoting bone formation.

Proteína Morfogenética Óssea 2/metabolismo , Periodonto/efeitos dos fármacos , Periodonto/metabolismo , Sinvastatina/farmacologia , Técnicas de Movimentação Dentária , Animais , Masculino , Ratos , Ratos Wistar
Shanghai Kou Qiang Yi Xue ; 16(5): 507-11, 2007 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-18004482


PURPOSE: To perform qualitative and quantitative analyses of core binding factor alpha1 (cbfalpha1) in periodontal tissue during the experimental rat tooth movement process and to investigate the active mechanism of cbfalpha1 in the osteoblast differentiation. METHODS: 42 male Wistar rats aged 8 weeks were divided into 7 groups (0,1,3,5,7,10 and 14 days groups) in random, 6 rats in each group. 42 rats were perfused and sacrificed at the 1st, 3rd, 5th, 7th, 10th and 14th day. All specimens were fixed, then proceeded with HE and cbfalpha1 immunohistochemical staining. The results were analyzed by SPSS11.0 software package for Dunnett test, and the histological changes of cbfalpha1 in periodontal tissue were evaluated. RESULTS: In the periodontal ligament(PDL) of non orthodontic treatment group, the expression of cbfalpha1 was lower; the expression of cbfalpha1 in every experimental groups increased firstly and decreased later; the expression of cbfalpha1 in the surface of the alveolar bone was lower in the compression side than in the tension side, and the number of positive cells was less too (P<0.01). CONCLUSION: cbfalpha1 participates in the process of bone remodeling during the process of orthodontic tooth movement, and it promotes the remodeling and stability of PDL.

Remodelação Óssea , Subunidades alfa de Fatores de Ligação ao Core/metabolismo , Técnicas de Movimentação Dentária , Animais , Masculino , Osteoclastos , Ligamento Periodontal , Periodonto , Ratos , Ratos Wistar