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Background: Multiple drug resistance protein 1 (MRP1), lung resistance protein (LRP), topoisomerase IIβ (TOPOIIβ) and B-cell lymphoma 2 (BCL2) are well known in the development of drug resistance in cancer cells. The aim of this study was to evaluate the relationship between them and the clinicopathological features, their expression differences between tumor tissue and experimental drug-resistant model in tongue carcinoma.Materials and Methods: Multiple drug resistance protein 1, LRP, TOPOIIβ, and BCL2 expression was examined by immunohistochemistry in specimens from radical surgeries of 65 patients with tongue carcinoma. A cisplatin-resistance cell line, SCC-15/cisplatin, was established from a cisplatin-sensitive cell line, SCC-15. A MTT-based method was used to analyze drug potencies. Immunofluorescence was used to detect protein expression in both cell lines. Western blot was used to compare the protein expressions in specimens and SCC-15/cisplatin cells.Results: We found higher expression of MRP1, LRP, and BCL2 and lower expression of TOPOIIβ in tongue carcinoma compared with adjacent non-neoplastic tongue tissues (P < 0.05). In addition, MRP1 and TopoIIβ expression were significantly associated with clinical stage, lymph node metastasis and histologic grade, and LRP was significantly associated with histologic grade in the samples (P < 0.05). Finally, Western blot showed that higher expressions of MRP1, LRP, and BCL2 and lower expression of TopoIIβ were observed in SCC-15/cisplatin cells than in clinical samples.Conclusion: Our results suggest that the high expressions of MRP1, LRP, and BCL2 and low expression of TOPOIIβ in patients with tongue carcinoma indicates that intrinsic drug resistance may exist in tongue carcinoma, and is associated with tumor differentiation and cisplatin resistance in tongue carcinoma. [ABSTRACT FROM AUTHOR]

Tauopathies are a class of neurodegenerative diseases that are characterized by pathological aggregation of tau protein, which is accompanied by synaptic disorders. However, the role of tau in endocytosis, a fundamental process in synaptic transmission, remains elusive. Here, we report that forced expression of human tau (hTau) in mouse cortical neurons impairs endocytosis by decreasing the level of the GTPase dynamin 1 via disruption of the miR-132-MeCP2 pathway; this process can also be detected in the brains of Alzheimer's patients and hTau mice. Our results provide evidence for a novel role of tau in the regulation of presynaptic function., (© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Impairments of dendritic trees and spines have been found in many neurodegenerative diseases, including Alzheimer's disease (AD), in which the deficits of melatonin signal pathway were reported. Melatonin receptor 2 (MT2) is widely expressed in the hippocampus and mediates the biological functions of melatonin. It is known that melatonin application is protective to dendritic abnormalities in AD. However, whether MT2 is involved in the neuroprotection and the underlying mechanisms are not clear. Here, we first found that MT2 is dramatically reduced in the dendritic compartment upon the insult of oligomer Aβ. MT2 activation prevented the Aβ-induced disruption of dendritic complexity and spine. Importantly, activation of MT2 decreased cAMP, which in turn inactivated transcriptional factor CCAAT/enhancer-binding protein α(C/EBPα) to suppress miR-125b expression and elevate the expression of its target, GluN2A. In addition, miR-125b mimics fully blocked the protective effects of MT2 activation on dendritic trees and spines. Finally, injection of a lentivirus containing a miR-125b sponge into the hippocampus of APP/PS1 mice effectively rescued the dendritic abnormalities and learning/memory impairments. Our data demonstrated that the cAMP-C/EBPα/miR-125b/GluN2A signaling pathway is important to the neuroprotective effects of MT2 activation in Aβ-induced dendritic injuries and learning/memory disorders, providing a novel therapeutic target for the treatment of AD synaptopathy., (© 2019 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

The two estrogen receptors (ERs), ERα and ERβ, mediate the diverse biological functions of estradiol. Opposite effects of ERα and ERβ have been found in estrogen-induced cancer cell proliferation and differentiation as well as in memory-related tasks. However, whether these opposite effects are implicated in the pathogenesis of Alzheimer's disease (AD) remains unclear. Here, we find that ERα and ERβ play contrasting roles in regulating tau phosphorylation, which is a pathological hallmark of AD. ERα increases the expression of miR-218 to suppress the protein levels of its specific target, protein tyrosine phosphatase α (PTPα). The downregulation of PTPα results in the abnormal tyrosine hyperphosphorylation of glycogen synthase kinase-3β (resulting in activation) and protein phosphatase 2A (resulting in inactivation), the major tau kinase and phosphatase. Suppressing the increased expression of miR-218 inhibits the ERα-induced tau hyperphosphorylation as well as the PTPα decline. In contrast, ERβ inhibits tau phosphorylation by limiting miR-218 levels and restoring the miR-218 levels antagonized the attenuation of tau phosphorylation by ERβ. These data reveal for the first time opposing roles for ERα and ERβ in AD pathogenesis and suggest potential therapeutic targets for AD., (© 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Background: The changes in Notch signaling are closely related to the occurrence and development of many cancers. We have investigated Notch signaling receptor and its ligand expressions in TSCC cell lines, tissues and its significance. We clarified Notch signaling pathway in TSCC and its mechanism. We regulated Notch signaling pathway of tumor cells, thereby inhibiting tumor cell proliferation and differentiation., Methods: We detected Jagged1 protein and mRNA expression levels in specimens (tongue cancer and adjacent tissues) from 74 patients with tongue cancer and in TSCC cell line. The Jagged1-targeted lentiviral vector RNAi system was constructed, and its suppressive effects on the proliferation and invasion of tongue carcinoma cells in in vivo and ex vivo were determined., Results: Jagged1 was expressed in tongue squamous cell cancer tissues and cell line, but there were differences in its expression. Jagged1 was knocked down and the tumor growth was inhibited accompanying cell cycle changes. Animal studies also showed that the tumor growth was inhibited., Conclusions: Jagged1 may be involved in the differentiation and proliferation of tongue cancer. Targeting Jagged1 RNA interference lentiviral vector can effectively lower Jagged1 mRNA and protein expression levels of Tca8113 cells, thereby preventing the proliferation of TSCC cells. Jagged1 is expected to be a promising new target for curing tongue cancer. In-depth study of the interaction between Jagged1 and other molecules of Notch signaling pathway in the process of carcinogenesis has important theoretical guidance and clinical significance in revealing the mechanism of Jagged1 and its application in the therapy for tongue cancer., (© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

Background: Ameloblastoma, a common odontogenic tumor located in jaws, generally leads to severe damage to patient's complexion and masticatory function. To expand in jaws, ameloblastoma must have a mechanism of resorbing the surrounding bone. Our objective was to explore the bone-resorption mechanism of ameloblastoma by observing the role of Receptor activator of nuclear factor kappa B ligand (RANKL) and matrix metalloproteinase-9 (MMP-9) in the bone-resorption process., Methods: In the study, the expression of RANKL and MMP-9 in ameloblastoma was detected using immunohistochemistry (IHC) and RT-PCR. Then, co-culture system of ameloblastoma cells and bone marrow cells from neonatal rabbit was erected to observe the potential of ameloblastoma cells to induce osteoclastogenesis. Finally, the induced osteoclasts were used for in vitro bone-resorption assay. In the co-culture system and the bone-resorption assay, the selective inhibitor of RANKL and MMP-9, osteoprotegerin (OPG) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were, respectively, used for observing the role of RANKL and MMP-9., Results: The expression of RANKL and MMP-9 in ameloblastoma was confirmed. Ameloblastoma cells were found to induce bone marrow cells from neonatal rabbit differentiate into osteoclasts with bone-resorption activity. In addition, OPG was found to, respectively, have markedly inhibitory effect on osteoclastogenesis (P<0.01), and slightly inhibitory action on bone resorption (P<0.05)., Conclusions: Ameloblastoma cells had the potential to induce osteoclastogenesis. Moreover, RANKL played an essential role in the in vitro osteoclast formation and bone resorption induced by ameloblastoma cells., (© 2010 John Wiley & Sons A/S.)

Background: Ameloblastoma is a frequently encountered odontogenic benign tumor characterized by local invasiveness and high risk of recurrence. Matrix metalloproteinase (MMP)-2 can degrade type IV collagen, one of the major components in the basement membrane, resulting in the promotion of tumor invasion, whereas it is under the influence of an activator, membrane type 1-MMP-14 and the tissue inhibitor of metalloproteases (TIMP)-2. The aim of this study was to investigate combinatorial role played by MMP-2, TIMP-2 and MMP-14 in ameloblastoma., Methods: Transcriptional expression of MMP-2, TIMP-2 and MMP-14 in tissue extracts of 42 ameloblastomas and 10 dental follicles was detected using reverse transcription-polymerase chain reaction, and compared difference in clinical type and local recurrence of ameloblastoma., Results: MMP-2, TIMP-2 and MMP-14 mRNA were detected in all investigated ameloblastoma tissues. While MMP-2 mRNA was only expressed in eight of 10 odontotheca tissues and TIMP- 2 and MMP-14 were not found in all odontotheca tissues. The mRNA expression of MMP-2, TIMP-2 and MMP-14 were significantly higher in ameloblastoma tissues than in odontotheca tissues. The mRNA levels of TIMP-2 and MMP-14 were significantly higher in recurrent and solid/multicystic ameloblastoma tissues than in primary and unicystic ameloblastoma tissues respectively., Conclusions: Of the MMP-2/TIMP-2/MMP-14 complex, a high expression of MMP-2, TIMP-2 and MMP-14 mRNA levels may contribute to the local invasive characteristics of ameloblastoma, whereas the local invasive capacity of ameloblastoma is more likely related to a high transcriptional levels of TIMP-2 and MMP-14.

Background: Ameloblastoma is an odontogenic benign tumor characterized by local invasiveness and most of its local recurrences clinically result from local invasion. This study used matrix metalloproteinase-2 (MMP-2) inhibitor I (MMP-2I) to investigate the role played by MMP-2 activity in the local invasiveness of ameloblastoma., Methods: The cells and xenografts of ameloblastoma were treated with MMP-2I and treatment group were compared with the control group. In vitro, the invasive activity of tumor cells was assayed in transwell cell culture chamber. Gelatinolytic activity of gelatinases and MMP-2/tissue inhibitor of matrix metalloproteinase (TIMP-2) protein expression was detected using gelatin zymography and flow cytometry. The cell viability and adhesion were evaluated using methyl thiazol tetrazolium. In vivo, bilateral subrenal capsule xenograft transplantation of ameloblastoma was performed in 10 nude mice and the invasion of ameloblastoma into the renal parenchyma was observed., Results: Active-MMP-2 of conditioned media was significantly lower in treatment group than in the control group. Accordingly, potential of in vitro cell invasion, adhesion and in vivo tumor invasion were also significantly lower in the treatment group than in the control group., Conclusions: Inhibitor of MMP-2 activity suppressed the local invasive capability of ameloblastoma by decreasing MMP-2 activity. MMP-2 activity is in relation with invasive capacity of ameloblastoma.