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Nuclear factor erythroid-2 related factor-2 (NFE2L2 or NRF2) is a frequently mutated gene in esophageal squamous cell carcinoma (ESCC). However, the roles of NFE2L2 alterations in ESCC remain elusive. In order to elucidate this issue, 130 ESCC patients who underwent esophagectomy were enrolled. The majority of tumor tissues were positive for NRF2, which was significantly enriched in the nucleus of the primary tumor tissues compared with the noncancerous mucosae. Primary ESCC tumors positive for NRF2 tended to be positive for NAD(P)H quinone oxidoreductase 1 (NQO1) as the downstream target of NRF2. There was a positive correlation between NRF2 and NQO1 expression level in primary tumors. NQO1 staining in primary tumors with NRF2 nuclear expression was significantly stronger than that with NRF2 cytoplasmic expression. In addition, high concordance for the status of NRF2 expression between primary tumors and corresponding metastatic lesions was observed. Next, we found high expression of nuclear NRF2 (the proportion of nuclear NRF2 expression20% or nuclear NRF2 immunohistochemistry score20) predicted shorter overall survival in patients with dual-positive expression of NRF2 and NQO1. Captured-based targeted sequencing revealed that NFE2L2 somatic alterations were observed in 52.8% of ESCC patients with dual-positive expression of NRF2 and NQO1. NFE2L2 amplification and mutations within the DLG/ETGE motifs were seen more frequently in ESCC tumors with nuclear or nucleocytoplasmic expression of NRF2 compared with those with cytoplasmic expression of NRF2. We also found high expression of nuclear NRF2 plus the status of NFE2L2 alteration exhibited high performance in predicting prognosis of ESCC patients. Our study demonstrated that high nuclear NRF2 expression and NFE2L2 alterations were associated with poor prognosis of ESCC patients. These findings suggest that NRF2 signaling pathway might play vital roles in ESCC malignancy and the aberrant activation of NRF2 pathway predicts unfavorable prognosis in ESCC.

The prognosis for patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) remains poor, with a need for alternatives to current salvage therapies. Loncastuximab tesirine (ADCT-402) is an antibody-drug conjugate comprising a humanized anti-CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine dimer toxin. Presented here are final results of a phase 1 dose-escalation and dose-expansion study in patients with R/R B-NHL. Objectives were to determine the maximum tolerated dose (MTD) and recommended dose(s) for expansion and evaluate safety, clinical activity, pharmacokinetics, and immunogenicity of loncastuximab tesirine. Overall, 183 patients received loncastuximab tesirine, with 3 + 3 dose escalation at 15 to 200 µg/kg and dose expansion at 120 and 150 µg/kg. Dose-limiting toxicities (all hematologic) were reported in 4 patients. The MTD was not reached, although cumulative toxicity was higher at 200 µg/kg. Hematologic treatment-emergent adverse events were most common, followed by fatigue, nausea, edema, and liver enzyme abnormalities. Overall response rate (ORR) in evaluable patients was 45.6%, including 26.7% complete responses (CRs). ORRs in patients with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and follicular lymphoma were 42.3%, 46.7%, and 78.6%, respectively. Median duration of response in all patients was 5.4 months and not reached in patients with DLBCL (doses ≥120 µg/kg) who achieved a CR. Loncastuximab tesirine had good stability in serum, notable antitumor activity, and an acceptable safety profile, warranting continued study in B-NHL. The recommended dose for phase 2 was determined as 150 µg/kg every 3 weeks for 2 doses followed by 75 µg/kg every 3 weeks. This trial was registered at www.clinicaltrials.gov as #NCT02669017.

The present study aimed to elucidate the genetic features of multiple lung cancer (MLC) and identify effective molecular markers for diagnosis using next generation sequencing (NGS). The present data may also inform patient treatment and prognosis. A total of 35 lesions were obtained from 17 patients with MLC. Based on lesion histology and NGS, 13 cases of multiple primary lung cancer (MPLC) were identified and 4 cases were classified as intrapulmonary metastasis (IPM). All 4 patients with IPM exhibited an epidermal growth factor receptor (EGFR) mutation and synchronous mutation of at least one tumor suppressor gene. The frequency and percentage of EGFR mutations, accompanied with tumor suppressor genes, were significantly higher in patients with IPM compared with MPLC. Furthermore, a high EGFR-heterogeneity score and male sex were risk factors of IPM occurrence. There were significant differences in mean EGFR mutation abundance alone, mutations of tumor suppressor genes and mutations of EGFR combined with tumor suppressor genes between patients with adenocarcinoma (ADC) and adenocarcinoma in situ (AIS). In conclusion, histological characteristics combined with genetic alterations may be an effective method for the diagnosis of MPLC and IPM, and NGS may serve as a useful diagnostic tool. MLC exhibited unique molecular characteristics, including higher rates of EGFR mutations, EGFR driver mutations accompanied with tumor suppressor gene mutations and the absence of anaplastic lymphoma kinase mutations, which may help distinguish between patients with MPLC or IPM. The present study hypothesized that the mean frequency of EGFR mutations, mutations of tumor suppressor genes and mutations of both EGFR and tumor suppressor genes may serve an important role in the development of AIS to ADC. The results of the present study highlight the potential underlying mechanisms of lung ADC development, which may assist with future elucidation of effective treatments to prevent the progression of lung cancer.

Two new Cu(II)-based coordination polymers (CPs) {[Cu3(btc)2(bpfp)2(H2O)2](H2O)2}n (1, H3btc = 1,2,3-benzenetricarboxylic acid, bpfp = bis(4-pyridylformyl)piperazine) and {[Cu(cca)(bpfp)]·2H2O}n (2...

Molecular testing on advanced non-small cell lung cancer (NSCLC) often confront of limited specimen.The aim of the study is to compare the mutation frequency in adenocarcinoma samples with poor tumor cell content and the optimal samples, making the optimal strategy of mutation analysis.In this retrospective study, mutation status of EGFR, ALK, ROS1, BRAF, KRAS, RET, HER2, CMET, NRAS and PIK3CA in 1594 NSCLCs were tested by ARMS-PCR and qRT-PCR, consists of 790 cases of surgical specimens, 741 cases of small biopsies, 63 cases of cytology cell blocks. We analyzed the discrepancies in mutation frequency with optimal specimens and the suboptimal ones.Comparing the gene mutation frequency in optimal and suboptimal samples, only the EGFR mutation rates of surgical samples (12.5 %, 1 out of 8) with 10 % tumor cellularity was lower than in those with ≥ 10 % (57.1 %, 385 out of 674， p = 0.015). However, surgical specimens with low tumor cellularity (20 %) were comparable to the qualified samples. The mutation frequency of EGFR in biopsy specimens with poor specimen adequacy(20 %,10 %,5 %,200,100,50) were comparable to the qualified samples. Low tumor cellularity (20 %,10 %,5 %) and low tumor cell number (200,100,50) was not associated with mutational rate for ALK, ROS1, BRAF, KRAS, RET, HER2, CMET, NRAS and PIK3CA mutations in small biopsy samples.In clinical practice, specimen with low adequacy could attempt in gene mutation testing, including biopsy and surgical specimen. However, the amount of tumor for molecular testing should be reported and suboptimal samples with a negative EGFR mutation result should be considered for combination using of other mutation test method or repeat testing of an alternate tumor sample, especially for the surgical samples.

With the continuous expansion of the scale of cloud datacenters, high energy consumption has become a problem. Virtual machine (VM) consolidation is an effective method of energy management, but overly aggressive consolidation has caused issues such as high service level agreement violation (SLA) rates and excessive migrations. To reduce energy consumption while ensuring the quality of service of a datacenter, a VM dynamic consolidation strategy based on a gray model and an improved discrete particle swarm algorithm (GM-DPSO) is proposed. This strategy uses a gray prediction algorithm for load detection and adjusts the size of the threshold according to the load condition. Then, we select VMs for overloaded and underloaded hosts and complete the placement of VMs through a VM placement strategy based on an improved discrete particle swarm algorithm. This method aims to improve the load balance, establish a mapping between VMs and hosts, use particles to search for the best VM placement in the global scope, and reduce the probability of SLAV. Our algorithm considers the impact of VM migration on system energy consumption and service quality and takes sufficient measures to reduce the number of migrations. To verify the effectiveness and practicality of this strategy, experiments were conducted on actual workloads, and the results were compared with those of other strategies. The experimental results show that the GM-DPSO greatly improves service quality while reducing energy consumption and SLAV by 34.53% and 97.53%, respectively. The methods and theories in this paper provide strong theoretical and practical engineering guidance for large-scale cloud deployment.

Background: Rapamycin receptor inhibitors have been applied in the clinic and achieved satisfactory therapeutic effect recently. The mechanisms did not clearly show how the Celastrus orbiculatus Extracts (COE) inhibited the expression of the mammalian Target of Rapamycin (mTOR) in human gastric cancer cells. The aim of this study was to investigate whether the COE inhibited the metastasis through the mTOR signaling pathway in human gastric cancer MGC-803 cells. Methods: The abnormal expression level of mTOR protein was detected by immunohistochemistry in human gastric cancer tissue. The MGC-803/mTOR- cells were constructed by knockdown of mTOR using lentivirus infection technique. The human gastric cancer MGC-803/mTOR- cells were treated with different concentrations (20, 40, 80 μg/ml) of COE for 24 hours. The ability of cell metastasis was analyzed by the cell invasion and migration assay. The expression levels of PI3K/Akt/mTOR signaling pathway were detected by Western Blotting. Results: COE inhibited the proliferation, invasion and migration of MGC-803/mTOR- cells in a concentrationdependent manner. The expression of E-cadherin protein increased, and the expression of N-cadherin and Vimentin decreased simultaneously in the MGC-803/mTOR- cells. 4EBP1, p-4EBP1, P70S6k, p-P70S6k, mTOR, p-mTOR, PI3K and Akt proteins in MGC-803/mTOR- cells were reduced in a dose-dependent manner. Conclusion: COE could not only inhibit cell growth, invasion and migration, but also inhibit the epithelialmesenchymal transition of gastric cancer cells. The molecular mechanism of COE inhibited the metastasis which may be related to the PI3K/Akt/mTOR signal pathway. This study provides ideas for the development of new anti-gastric cancer drugs.

Glucoside xylosyltransferase2 (GXYLT2), a member of the human α-1,3- D -xylosyltransferases, functions to modify the first xylose to the O-Glucose residue on epidermal growth factor (EGF) repeats of Notch receptors. It is well-established that the Notch signaling pathway plays a critical role in proper development and homeostasis. However, the regulatory role of EGF xylosylation in Notch signaling and different cell activities in human cells remains unknown. In this study, we showed that knockdown of GXYLT2 suppressed human cell proliferation and induced G1/S phase cell cycle arrest. GXYLT2 downregulation also inhibited cell migration and invasion, whereas the overexpression of GXYLT2 had the opposite effects. Additionally, GXYLT2 activated Notch signaling and promoted the phosphorylation of MAPKs but not PI3K and Akt. Taken together, our findings indicated that GXYLT2 plays an important role in cell activities via regulation of the Notch signaling.

Background Circulating microRNAs (miRNAs) have emerged as potential biomarkers for cardiovascular diseases. However, few studies have focused on the role of exosomal miRNAs in acute coronary syndrome (ACS). The purpose of this study was to explore weather serum exosomal microRNA-146a (exo-miR-146a) could be used as a novel diagnostic biomarker for ACS and to investigate its relationship with inflammatory response. Methods A total of 63 ACS patients and 25 patients with normal coronary arteries (Control) were enrolled respectively. The serum exosomes were isolated and then identified by transmission electron microscopy (TEM), western blot, and nanoparticle tracking analysis (NTA). The expression levels of exo-miR-146a in serum were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and the expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in serum were assessed by enzyme-linked immunosorbent assay (ELISA). Spearman's correlation analysis was used to appraise the potential factors related to serum exo-miR-146a and receiver operating characteristic (ROC) curve analysis was applied for predicting the accuracy of ACS via the area under curve (AUC). Results Exosomes isolated from serum were of typical cup-like shape, with 50-150 nm diameter, and expressed CD9, CD63, CD81, and HSP70. The expression levels of serum exo-miR-146a, IL-1β, IL-6, and TNF-α were significantly increased in ACS patients compared with the control group, Spearman's correlation analysis indicated that exo-miR-146a expression was markedly positively correlated with IL-1β, IL-6, and TNF-α. The ROC curve analyses revealed that exo-miR-146a could distinguish ACS patients from their normal controls. Conclusions The serum exo-miR-146a may be used as a novel diagnostic biomarker for ACS patients, and it is also associated with inflammatory response.

Background Homologous recombination repair gene (HRR) mutations have been proven to be effective biomarkers for PARP inhibitor therapy for metastatic castration resistant prostate cancer. However, the frequency of HRR mutations in patients with localized and locally advanced prostate cancer is still unclear. This study investigated the profile of HRR gene mutations in Chinese localized and locally advanced prostate cancer patients. Materials and Methods 74 patients with localized and locally advanced prostate cancer patients in Beijing Chaoyang Hospital between May 2018 and September 2019 were retrospectively included. Matched prostate cancer and histologically normal tissues were subjected to next-generation sequencing. Pathogenic alterations of 19 HRR genes were examined. Results Ten deleterious and suspected deleterious mutations (4 germline and 6 somatic mutations) were detected in 9 of 74 (12.16 %) patients, occurred in seven HRR-related genes, including CDK12, NBN, ATM, ATR, BRCA2, PALB2 and RAD51C. The mutation frequency of HRR genes in this study (12.16 %) was higher than TCGA cohort (7.29 %), and the mutation sites in 7 HRR genes detected in this cohort were different from those of TCGA data. Patients with HRR gene mutations had higher Gleason grade (≥ 3) (P = 0.03) and risk level (very-high) (P = 0.03). Postoperative prostate specific antigen level and positive surgical margin rate was not associated with HRR gene mutation status. Conclusions This study illustrated the mutation patterns of HRR genes in Chinese population with localized and locally advanced prostate cancer. These results provide further evidence that HRR gene mutations were more prevalent in patients with higher Gleason grade, or with very-high-risk level. Patients with these clinicopathologic characteristics may need more precise stratification through molecular detection.

The rational targeting of a transcription factor, interferon regulatory factor 5 (IRF5), inhibits downstream functions., The transcription factor interferon regulatory factor 5 (IRF5) plays essential roles in pathogen-induced immunity downstream of Toll-, nucleotide-binding oligomerization domain–, and retinoic acid–inducible gene I–like receptors and is an autoimmune susceptibility gene. Normally, inactive in the cytoplasm, upon stimulation, IRF5 undergoes posttranslational modification(s), homodimerization, and nuclear translocation, where dimers mediate proinflammatory gene transcription. Here, we report the rational design of cell-penetrating peptides (CPPs) that disrupt IRF5 homodimerization. Biochemical and imaging analysis shows that IRF5-CPPs are cell permeable, noncytotoxic, and directly bind to endogenous IRF5. IRF5-CPPs were selective and afforded cell type– and species-specific inhibition. In plasmacytoid dendritic cells, inhibition of IRF5-mediated interferon-α production corresponded to a dose-dependent reduction in nuclear phosphorylated IRF5 [p(Ser462)IRF5], with no effect on pIRF5 levels. These data support that IRF5-CPPs function downstream of phosphorylation. Together, data support the utility of IRF5-CPPs as novel tools to probe IRF5 activation and function in disease.

The aim of the current study was to investigate the effect of adipocytes on the differentiation of osteoblasts at different stages of adipocyte development.BMSCs were isolated from 4-week-old male wistar rat femurs and tibias, and flow cytometry was performed. Adipocytes were derived from BMSCs, cell morphology was continually observed from day 21 to day 50. Adipocyte medium was collected once every 2days (d) and ELISA kits were used for detection of triglycerides (TG), tumor necrosis factor-α (TNF-α), and interleukin-6(IL-6) expression level. 21d and 40d old adipocyte and osteoblast cells were co-cultured, and alizarin red staining was performed after 21d. After co-culture, the adherent cells were collected, and the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) was detected by real time PCR.Results of cell characterisation showed that the cells had positive expression of CD29 (97.92%) and CD44 (89.32%). With the increase of the induction time of mature adipocytes, the number of adipocyte on 21thd was significantly higher than 40thd, while the volume of adipocyte was significantly lower than 40thd (P0.05). The levels of TG(2.6±0.83mmol/l VS 3.8±0.66mmol/l), TNF-α(30.5±2.53pg/ml VS 57.6±5.1pg/ml), and IL-6(32.5±1.42pg/ml VS 55.1±5.97pg/ml) secreted by adipocytes increased with induction time: 40thd was significantly higher than 21thd (P0.01). When 21thd adipocytes and osteoblasts were co-cultured, the number of calcium nodules significantly increased over that of the positive control group, When 40thd adipocytes and osteoblasts were co-cultured, the number of calcium nodules significantly decreased over that of the positive control group (P0.05). The OPG(68.9±5.39 VS 1.00±0.36) expression was significantly increased, and the expression of RANKL (2.0±0.84 VS 34.4±2.01) was significantly decreased from the 21thd adipocytes co-cultured group compared with the 40thd adipocytes co-cultured group (P0.001).The differential size of adipocytes in the bone marrow can affect bone metabolism by regulating the expression of OPG/RANKL.

In this paper, a numerical solution of fractional-order time-varying delayed differential systems using Lagrange interpolation is investigated. Based on Lagrange interpolation method, the Adams–Bashforth–Moulton algorithm has been extended to solve fractional-order time-varying delayed differential systems. Furthermore, a detailed error analysis of this algorithm is presented. A fractional-order time-varying delayed Hopfield neural network as numerical example is given. In addition, the different parameters in the fractional-order time-varying delayed neural network are considered. Finally, some simple and direct numerical methods which are compared with Lagrange interpolation method in the fractional-order time-varying delayed neural network are discussed. The example with numerical simulation clearly illustrated that the present method is reliable.

This paper focuses on the parameter estimation problem of fractional-order neural network. By combining the adaptive control and parameter update law, we generalize the synchronization-based identification method that has been reported in several literatures on identifying unknown parameters of integer-order systems. With this method, parameter identification and synchronization can be achieved simultaneously. Finally, a numerical example is given to illustrate the effectiveness of the theoretical results.

The aim of the current study was to investigate the effects of obesity, induced via a high-fat diet, on bone metabolism in rats.Two hundred healthy Wistar male rats aged 4 weeks were fed a standard diet and a high-fat diet. At specific time points (week 0, 4, 6, 8, and 10), plasma was collected to determine the levels of glucose and lipid metabolism. Additionally, enzyme-linked immunoassays were performed to determine the plasma levels of adipocyte and bone metabolism factors. Micro-CT imaging was used to determine the parameters of bone metabolism. At 10th week, immunohistochemistry evaluation of femoral bone samples was performed to determine the expression of adipocyte factors.Receptor activator of nuclear factor kB ligand (RANKL) was positively correlated with levels of triglyceride (TG), free fatty acids (FFA), and tumor necrosis factor alpha (TNF-α) (P0.05), while receptor activator of the NF-κB (RANK) showed a positive correlation with TG, FFA, TNF-α and leptin (LPT) (P0.05). CT imaging demonstrated that bone mineral density and trabecular thickness were elevated compared to controls before 6 weeks, but these values were found to be lower in rats fed a high fat diet in the following weeks (P0.05). Immunohistochemistry showed that the expression of TNF-α, Interleukin- 6 (IL-6) and peroxisome proliferator activated receptor-γ (PPAR-γ) were increased and the expression of adiponectin (APN) were diminished in rats fed a high-fat diet compared to controls at 10 weeks (P0.05).With obesity intensifies, the release of FFA cause inflammation factor increase, resulting in bone parameters decreased.

In opinion dynamics, the convergence of the heterogeneous Hegselmann-Krause (HK) dynamics has always been an open problem for years which looks forward to any essential progress. In this short note, we prove a partial convergence conclusion of the general heterogeneous HK dynamis. That is, there must be some agents who will reach static states in finite time, while the other opinions have to evolve between them with a minimum distance if all the opinions does not reach consensus. And this result leads to the convergence of two special case of heterogeneous HK dynamics: the minimum confidence threshold is large enough, or the initial opinion difference is small enough., 6pages,no figure

Background Higher probability of T2DM in Uygur population is due to greater values of WHR and visceral fat content. This study aimed to investigate the association between DNA methylation of APN, TNF-α, MCP-1 of visceral adipose tissue and T2DM. Methods Visceral adipose tissue was collected from Uygur population, and divided them into normal control group (NC, n = 50), obesity group(Ob, n = 48)and T2DM group(n = 26). mRNA expression of TNF-α, APN and MCP-1 was quantified by RT-PCR; DNA methylation status was detected by denaturing high performance liquid chromatography(DHPLC). Results Among the NC, Ob and T2DM group, methylation-positive rate of APN was gradually increased (34.0%, 47.9%, 65.4%) (P

Synchronization for incommensurate Riemann–Liouville fractional competitive neural networks (CNN) with different time scales is investigated in this paper. Time delays and unknown parameters are concerned in the model, which is more practical. Two simple and effective controllers are proposed, respectively, such that synchronization between the salve system and the master system with known or unknown parameters can be achieved. The methods are more general and less conservative which can also be applied to commensurate integer-order systems and commensurate fractional systems. Furthermore, two numerical ensamples are provided to show the feasibility of the approach. Based on the chaotic masking method, the example of chaos synchronization application for secure communication is provided.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates collagen-mediated platelet activation through its cytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIMs). However, the function of CEACAM1’s extracellular cleavage fragments is currently unknown. In the present study, we used mass spectrometry (MS) to identify 9 cleavage fragments shed by matrix metallopeptidase 12 (MMP-12), and then we synthesized peptides with sequences corresponding to the fragments. QLSNGNRTLT (QLSN), a peptide from the A1-domain of CEACAM1, significantly attenuated collagen-induced platelet aggregation. QLSN also attenuated platelet static adhesion to collagen. Additionally, QLSN reduced human platelet secretion and integrin αIIbβ3 activation in response to glycoprotein VI (GPVI)–selective agonist, convulxin. Correspondingly, QLSN treatment significantly decreased convulxin-mediated phosphorylation of Src, protein kinase B (Akt), spleen tyrosine kinase (Syk) and phospholipase Cγ2 (PLCγ2) in human platelets. These data indicate that the CEACAM1-derived peptide QLSN inhibits GPVI-mediated human platelet activation. QLSN could potentially be developed as a novel antiplatelet agent. QLSN inhibit collagen-induced human platelet activation through glycoprotein VI.

MicroRNAs (miRs) play an essential role in the regulation of bone formation and homeostasis. miR-185 has been reported to negatively regulate osteogenesis in vitro. However, whether it has an impact on in vivo bone homeostasis remains unknown. Here, we demonstrated that primary osteoblasts and mesenchymal stem cells derived from miR-185-knockout (KO) mice exhibited enhanced osteogenesis. Further, we constructed an ovariectomized mouse model to investigate the role of miR-185 during osteoporosis. Micro-computed tomography revealed an increased bone volume in KO compared to wild-type mice 6 weeks after surgery, indicating redundant bone formation after miR-185 depletion. Dual-luciferase reporter assays identified biglycan (Bgn), which promotes bone formation through the BMP/Smad pathway, as the direct target of miR-185. Taken together, these findings indicate that blocking miR-185 expression increases bone formation during osteoporosis, which may partly occur through the regulation of Bgn expression and BMP/Smad signaling.

Synchronization for Riemann-Liouville fractionalorder competitive neural networks with different time scales is concerned in this paper. An incommensurate fractional-order chaotic competitive neural network with different time scales is given. Based on the theory of Riemann-Liouville fractional calculus, a simple and effective controller is proposed. Finally, a numerical examples is presented to illustrate the effectiveness of the approach.

Regulation of microRNAs (miRNA) has been extensively investigated in diseases; however, little is known about the roles of miRNAs in cleidocranial dysplasia (CCD). The aim of the present study was to investigate the potential involvement of miRNAs in CCD. In vitro site-directed mutagenesis was performed to construct three mutant Runx2 expression vectors, which were then transfected into LS8 cells and MC3T3-E1 cells, to determine the impact on amelogenesis and osteogenesis, respectively. miRCURY LNA miRNA microarray identify miR-185-5p as a miRNA target commonly induced by all three Runx2 mutants. Real-time quantitative PCR was applied to determine the expression of miR-185-5p and Dlx2 in samples. Dual-luciferase reporter assays were conducted to confirm Dlx2 as a legitimate target of miR-185-5p. The suppressive effect of miR-185-5p on amelogenesis and osteogenesis of miR-185-5p was evaluated by RT-PCR and western blot examination of Amelx, Enam, Klk4, and Mmp20 gene and protein expression, and by Alizarin Red stain. We found that mutant Runx2 suppressed amelogenesis and osteogenesis. miR-185-5p, induced by Runx2, suppressed amelogenesis and osteogenesis. Furthermore, we identified Dlx2 as direct target of miR-185-5p. Consistently, Dlx2 expression was inversely correlated with miR-185-5p levels. This study highlights the molecular etiology and significance of miR-185-5p in CCD, and suggests that targeting miR-185-5p may represent a new therapeutic strategy in prevention or intervention of CCD.