bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR‐377‐5p inhibits lung cancer cell proliferation, invasion, and cell cycle progression by targeting AKT1 signaling
Authors: Wu Han , Liu Hai Yan , Liu Wen Jie , Shi Yong Li , Bao Dawei 
Published: November 2018

AbstractLung carcinoma is the most common type of malignant tumors globally, and its molecular mechanisms remained unclear. With the aim to investigate the effects of microRNA (miR)‐377‐5p on the cell development, invasion, metastasis, and cycle of lung carcinoma, this study was performed. We evaluated miR‐377‐5p expression levels in lung cancer tissues and cell models. Cell viability, proliferation, migration, invasion abilities, and cell cycle distribution were measured using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, crystal violet, transwell, and flow cytometry assay. Furthermore, expression levels of protein kinase B α subunit (AKT1) and proteins related to cell cycle and epithelial‐mesenchymal transition (EMT) were assessed using Western blot analysis and quantitative real‐time polymerase chain reaction. These results suggested that miR‐377‐5p was downregulated in vivo and in cell models, and miR‐377‐5p overexpression inhibited cell viability, proliferation, migration, invasion, and induced cell‐cycle arrest. In addition, as a target of miR‐377‐5p, AKT1 alleviated the decreases of cell viability, proliferation, migration, invasion, the S‐phase cells, the expression of cyclin D1, fibronectin, and vimentin, as well as the increases of the G0/G1‐phase cells, the expression of Foxo1, p27
kip1, p21
Cip1 and E‐cadherin when miR‐377‐5p overexpressed. In conclusion, miR‐377‐5p inhibited cell development and regulated cell cycle distribution and EMT by targeting AKT1, which provided a theoretical basis for further study of lung carcinoma therapeutics.
Epigenetic and metabolic alterations in human amniotic fluid stem cells induced to cardiomyogenic differentiation by DNA methyltransferases and p53 inhibitors
Authors: Gasiūnienė Monika , Zubova Anastasija , Utkus Algirdas , Navakauskienė Rūta 
Published: November 2018

AbstractHuman amniotic fluid‐derived mesenchymal stem cells (AF‐MSCs) may be a valuable source for cell therapy and regenerative medicine. In this study, the potential of DNA methyltransferases (DNMT) inhibitors Decitabine, Zebularine, RG108 alone or combined with Zebularine and p53 inhibitor Pifithrin‐α to induce cardiomyogenic differentiation of AF‐MSCs was investigated. Differentiation into cardiomyocyte‐like cells initiation was indicated with all agents by changes in the cell phenotype, upregulation of the relative expression of the main cardiac genes (NKX2‐5,
TNNT2,
MYH6, and
DES) as well as of cardiac ion channels genes (sodium, calcium, and potassium) as determined by reverse‐transcription quantitative polymerase chain reaction and the increase in Connexin43 levels as detected from Western blot and immunofluorescence data. Cellular energetics and mitochondrial function in induced cells were assessed using Seahorse analyzer and revealed the initiation of AF‐MSCs metabolic transformation into cardiomyocyte‐like cells. All used inducers were nontoxic to AF‐MSCs, arrested cell cycle at the G0/G1 phase, and upregulated p53 and p21 expression. The relative expression of miR‐34a and miR‐145 that are related to cell cycle regulation was also observed. Furthermore, the evaluated levels of chromatin remodeling proteins enhancer of zeste homolog 2, suppressor of zeste 12 protein homolog, DNMT1, histone deacetylase 1 (HDAC1), HDAC2, and heterochromatin protein 1α, as well as the rate of activating histone modifications, exhibited rearrangements of chromatin after the induction of cardiomyogenic differentiation. In conclusion, we demonstrated that all explored DNMT and p53 inhibitors initiated cardiomyogenesis‐related alterations in AF‐MSCs through rather similar mechanisms but to a different extent providing useful insights for the future research and potential applications of AF‐MSCs.
Carvacrol suppresses inflammatory responses in rheumatoid arthritis fibroblast‐like synoviocytes
Authors: Li Yu , Xu Jian‐zhong , Gu Chen‐xi , Liu Guan‐lei , Tian Ke 
Published: November 2018

AbstractBackgroundFibroblast‐like synoviocytes (FLSs) play an essential role in the chronic inflammatory process of rheumatoid arthritis (RA). Carvacrol is a natural monoterpenic phenol that retains significant anti‐inflammatory activity. However, the effect of carvacrol on inflammatory response in RA‐FLSs has not yet been reported. The present study aimed to investigate the role of carvacrol in lipopolysaccharides (LPS)‐induced inflammatory response in human RA‐FLSs.MethodsCell viability and proliferation were measured by MTT and Cell Counting Kit‐8 assays, respectively. The migration was detected by transwell assay. The production of inflammatory cytokines and matrix metalloproteinases (MMPs) were analyzed by enzyme‐linked immunosorbent assay. The expressions of toll‐like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), NF‐κB, p38, p‐p38, ERK1/2, p‐ERK1/2, c‐Jun N‐terminal kinase (JNK), and p‐JNK were detected by Western blot analysis.ResultsCarvacrol‐inhibited LPS‐induced cell proliferation and migration of RA‐FLSs. The production of inflammatory cytokines, including tumor necrosis factor alpha, interleukin (IL)− 6, and IL‐8, was reduced by carvacrol in LPS‐induced RA‐FLSs. Meanwhile, the induction of MMPs, including MMP‐1, MMP‐3, and MMP‐13, caused by LPS stimulation was inhibited by carvacrol in RA‐FLSs. Furthermore, carvacrol prevented LPS‐induced activation of the TLR4/MyD88/NF‐κB, p38, and ERK1/2 pathways in RA‐FLSs.ConclusionsCarvacrol‐mitigated LPS‐induced cell proliferation, migration, and inflammation in RA‐FLSs. The TLR4/MyD88/NF‐κB, p38 and ERK1/2 pathways might be involved in the protective effect of carvacrol.
Transient receptor potential melastatin 2–antisense RNA is overexpresed in osteosarcoma and regulates cell proliferation and apoptosis
Authors: Geng Jie , Lu Ming , Li Wuyin 
Published: November 2018

AbstractAccumulating evidence suggested that transient receptor potential melastatin 2–antisense RNA (TRPM2‐AS) played crucial roles in the progression of human cancers. However, the role of TRPM2‐AS was still unknown in osteosarcoma. The aim of this study was to explore the clinical significance of TRPM2‐AS in osteosarcoma patients, and determine the role of TRPM2‐AS on osteosarcoma cell proliferation and apoptosis. In our results, we identified a novel oncogenic long noncoding RNA TRPM2‐AS, which was overexpressed in osteosarcoma tissues and cells, and correlated with advanced Enneking stage, large tumor size and high histological grade in osteosarcoma cases. Survival analysis indicated that osteosarcoma patients with high TRPM2‐AS expression had an obviously shorter overall survival time than those with low TRPM2‐AS expression. Loss‐of‐function studies suggested that suppression of TRPM2‐AS expression inhibited osteosarcoma cell proliferation and induced cell apoptosis through upregulating cleaved caspase‐3 and cleaved caspase‐9 expression. In conclusion, TRPM2‐AS acts as an oncogenic long noncoding RNA and predicts poor prognosis in osteosarcoma.
A panel of noncoding RNAs in non–small‐cell lung cancer
Authors: Bagheri Abouzar , Khorshid Hamid Reza Khorram , Tavallaie Mahmood , Mowla Seyed Javad , Sherafatian Masih , Rashidi Mohsen , Zargari Mehryar , Boroujeni Mahdi Eskandarian , Hosseini Sayed Mostafa 
Published: November 2018

AbstractNon–small‐lung cancer (NSCLC) is the leading cause of cancer death. Early detection of NSCLC could pave the way for effective therapies. Analysis of molecular genetic biomarkers in biological fluids has been proposed as a useful tool for cancer diagnosis. Here, we aimed to develop a panel of noncoding RNAs (ncRNAs) in sputum for NSCLC early detection. Expression of 11 ncRNAs were analyzed by real–time polymerase chain reaction in sputum samples of 30 NSCLC patients and 30 sex‐ and age‐matched cancer‐free controls. Stability of endogenous microRNAs (miRNAs) in sputum was evaluated after 3 and 6 days at 4°C, 6 months, and 1 year at −80°C. Nine ncRNAs showed significant differences of their expression in sputum between NSCLC patients and controls. A logistic regression model with the best prediction was built based on miR‐145, miR‐126, and miR‐7. The composite of the three miRNAs produced 90% sensitivity and specificity in distinguishing NSCLC patients from the controls. Results indicate that miRNAs could be useful biomarkers based on their stability under various storage conditions and maintain differential changes between cancer and control groups. Moreover, measurement of miRNAs in sputum could be a noninvasive approach for detection of lung cancer.
MicroRNA‐194 overexpression protects against hypoxia/reperfusion‐induced HK‐2 cell injury through direct targeting Rheb
Authors: Shen Yan , Zhao Yan , Wang Lijun , Zhang Wenjing , Liu Chao , Yin Aiping 
Published: November 2018

AbstractRenal ischemia‐reperfusion injury, a major cause of renal failure, always leads to acute kidney injury and kidney fibrosis. MicroRNAs (miRs) have been reported to be associated with renal ischemia‐reperfusion injury. miR‐194 was downregulated following renal ischemia‐reperfusion injury; however, the function and mechanism of miR‐194 in renal ischemia‐reperfusion injury have not yet been fully understood. In the present study, we constructed renal ischemia‐reperfusion injury model in vitro through treatment of human kidney proximal tubular epithelial cells HK‐2 by hypoxia/reperfusion (H/R). We observed that miR‐194 was decreased in H/R‐induced HK‐2 cells. miR‐194 mimic increased H/R‐induced HK‐2 cell survival, whereas miR‐194 inhibitor further strengthened H/R‐ inhibited HK‐2 cell survival. Also, we observed that miR‐194 overexpression suppressed oxidative stress markers, including malondialdehyde, glutathione, and secretion of pro‐inflammatory cytokines, including IL‐6, IL‐1β, and TNF‐α; however, miR‐194 inhibitor showed the reverse effects. Results from dual‐luciferase analysis confirmed that Ras homology enriched in brain (Rheb) was a direct target of miR‐194. Finally, we corroborated that miR‐194 affected cell growth, oxidative stress, and inflammation through targeting Rheb in H/R‐induced HK‐2 cells. In conclusion, our results suggested that miR‐194 protect against H/R‐induced injury in HK‐2 cells through direct targeting Rheb.
Retracted: MicroRNA‐373 promotes the development of endometrial cancer by targeting LATS2 and activating the Wnt/β‐Catenin pathway
Authors: Li Yan , Sun Dongxia , Gao Jie , Shi Zhimin , Chi Pengyu , Meng Yuanyuan , Zou Changjun , Wang Yanhua 
Published: November 2018

AbstractIn the female reproductive tract, endometrial cancer is the most common malignant tumor. Recently, the specific functions of many miRNAs have been identified in endometrial cancer. However, the contradictory effects of microRNA‐373 (miR‐373) in different human cancers draw our attention. In the present research, upregulation of miR‐373 was identified in endometrial cancer which predicted poor prognosis. Moreover, upregulation of miR‐373 promoted the migration, invasion, and proliferation of endometrial cancer cells. To further confirm that results, the EMT and Wnt/β‐Catenin pathways were also investigated, which were promoted by overexpression of miR‐373. Then, we further investigate the downstream factor, large tumor suppressor kinase 2 (LATS2) which was inhibited by miR‐373. LATS2 was verified as a direct target gene of miR‐373 through luciferase reporter assay. Especially, the facilitation of miR‐373 for cell proliferation, migration and invasion was impaired by LATS2. Taken together, miR‐373 promotes the progression of endometrial cancer through targeting LATS2 and promoting EMT and Wnt/β‐Catenin pathway.
Selenoprotein S protects against high glucose‐induced vascular endothelial apoptosis through the PKCβII/JNK/Bcl‐2 pathway
Authors: Yu Shanshan , Liu Xiaoying , Men Lili , Yao Junjie , Xing Qian , Du Jianling 
Published: November 2018

AbstractVascular endothelial apoptosis is closely associated with the pathogenesis and progression of diabetic macrovascular diseases. Selenoprotein S (SelS) participates in the protection of vascular endothelial and smooth muscle cells from oxidative and endoplasmic reticulum stress‐induced injury. However, whether SelS can protect vascular endothelium from high glucose (HG)‐induced apoptosis and the underlying mechanism remains unclear. The present study preliminarily analyzed aortic endothelial apoptosis and SelS expression in diabetic rats in vivo and the effects of HG on human umbilical vein endothelial cell (HUVEC) apoptosis and SelS expression in vitro. Subsequently, SelS expression was up‐ or downregulated in HUVECs using the pcDNA3.1‐SelS recombinant plasmid and SelS‐specific small interfering RNAs, and the effects of high/low SelS expression on HG‐induced HUVEC apoptosis and a possible molecular mechanism were analyzed. As expected, HG induced vascular endothelial apoptosis and upregulated endothelial SelS expression in vivo and in vitro. SelS overexpression in HUVECs suppressed HG‐induced increase in apoptosis and cleaved caspase3 level, accompanied by reduced protein kinase CβII (PKCβII), c‐JUN N‐terminal kinase (JNK), and B‐cell lymphoma/leukemia‐2 (Bcl‐2) phosphorylation. In contrast, inhibiting SelS expression in HUVECs further aggravated HG‐induced increase in apoptosis and cleaved caspase3 level, which was accompanied by increased PKCβII, JNK, and Bcl‐2 phosphorylation. Pretreatment with PKC activators blocked the protective effects of SelS and increased the apoptosis and cleaved caspase3 level in HUVECs. In summary, SelS protects vascular endothelium from HG‐induced apoptosis, and this was achieved through the inhibition of PKCβII/JNK/Bcl‐2 pathway to eventually inhibit caspase3 activation. SelS may be a promising target for the prevention and treatment of diabetic macrovascular complications.
Identification of key biomarkers in diabetic nephropathy via bioinformatic analysis
Authors: Zeng Mengru , Liu Jialu , Yang Wenxia , Zhang Shumin , Liu Fuyou , Dong Zheng , Peng Youming , Sun Lin , Xiao Li 
Published: November 2018

AbstractDiabetic nephropathy (DN) is a major cause of end‐stage renal disease. Although intense efforts have been made to elucidate the pathogenesis, the molecular mechanisms of DN remain to be clarified. To identify the candidate genes in the progression of DN, microarray datasets GSE30122, GSE30528, and GSE47183 were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified, and function enrichment analyses were performed. The protein‐protein interaction network was constructed and the module analysis was performed using the Search Tool for the Retrieval of Interacting Genes and Cytoscape. A total of 61 DEGs were identified. The enriched functions and pathways of the DEGs included glomerulus development, extracellular exosome, collagen binding, and the PI3K‐Akt signaling pathway. Fifteen hub genes were identified and biological process analysis revealed that these genes were mainly enriched in acute inflammatory response, inflammatory response, and blood vessel development. Correlation analysis between unexplored hub genes and clinical features of DN suggested that COL6A3, MS4A6A,PLCE1, TNNC1, TNNI1, TNN2, and VSIG4 may involve in the progression of DN. In conclusion, DEGs and hub genes identified in this study may deepen our understanding of molecular mechanisms underlying the progression of DN, and provide candidate targets for diagnosis and treatment of DN.
Serum markers in the differential diagnosis of Waldenstrom macroglobulinemia and other IgM monoclonal gammopathies
Authors: Zou Hong , Yang Rong , Liao Zhong‐xian , Qin Tian‐di , Chen Ping , Zhang Bei‐ying , Cao Ying‐ping , Huang Hui‐fang 
Published: November 2018

BackgroundIgM monoclonal gammopathy can be present in a broad spectrum of diseases. We evaluated the value of serum markers in the differential diagnosis of Waldenstrom macroglobulinemia (WM) and other types of IgM monoclonal gammopathies.MethodsWe included patients who were first admitted to hospital and identified as having IgM monoclonal gammopathy by serum immunofixation electrophoresis (sIFE). We evaluated basic clinical features, sIFE, diagnosis, and serum markers. Furthermore, we applied the receiver operating characteristic (ROC) curve to analyze the differential diagnosis value of serum markers for WM. Finally, we used logistic regression and ROC curve to analyze the differential diagnosis value of multimarker combinations to identify WM.ResultsIgM monoclonal gammopathy was most frequently found in patients with Waldenstrom macroglobulinemia, followed by monoclonal gammopathy of undetermined significance (MGUS), B‐cell non‐Hodgkin Lymphoma (B‐NHL), and multiple myeloma (MM). Serum markers showed significant differences among the four diseases. The diagnostic markers LDH, IgM, IgG, IgA, and serum light chain К had higher diagnostic efficiency. Among these markers, serum IgM provided the highest diagnostic efficiency. Additionally, the combined use of all five serum markers provided the most effective diagnosis.ConclusionsThe five serum markers, LDH, IgM, IgG, IgA, and К, each yielded a specific efficacy in differential diagnosis of WM. The single marker with the highest diagnostic efficiency was the serum IgM level. However, a combination of multiple serum markers was better than the use of a single marker in diagnosing WM. The combined use of all five serum markers provided the most effective diagnosis, with an AUC of .952 and sensitivity and specificity of 87.8% and 86.9%, respectively.
Reasons for nonadherence and response to treatment in an adherence intervention trial for relapsing–remitting multiple sclerosis patients
Authors: Schoor Rachel , Bruce Amanda , Bruce Jared , Goggin Kathy , Schanfarber Bethany , Bradley‐Ewing Andrea , Thelen Joanie , Glusman Morgan , Lynch Sharon G. , Strober Lauren , Catley Delwyn 
Published: November 2018

AbstractObjectivesTo explore whether patients in an adherence trial who appeared not to take disease modifying therapy (DMT) for avoidance reasons could be reliably identified, by observational coding, for their main reason of not taking DMT. To determine whether reason groups could be distinguished by clinical and self‐report psychological characteristics and intervention outcomes.MethodParticipants were multiple sclerosis patients (N = 78, 88.5% female, mean age 45.64) demotivated to take DMT. Audio recordings of the sessions were coded for the main reason of not taking DMT. Reason groups were compared based on patient characteristics and intervention outcomes.ResultsAvoidance and three other reasons for not taking DMT (side effects, cost, and mild course) were reliably identified (κ = 0.88). Patient characteristics failed to distinguish participants in the Avoidance group, which also had poorer outcomes (X2 [2, n = 73] = 6.35, p = 0.036).ConclusionsPatients not taking DMT for avoidance reasons may need novel methods to identify them and encourage (re‐)initiation.
Downregulation of microRNA‐592 protects mice from hypoplastic heart and congenital heart disease by inhibition of the Notch signaling pathway through upregulating KCTD10
Authors: Pang Xue‐Feng , Lin Xue , Du Jian‐Jun , Zeng Ding‐Yin 
Published: November 2018

AbstractEvidence has demonstrated that the microRNA (miR) may play a significant role in the development of congenital heart disease (CHD). Here, we explore the mechanism of microRNA‐592 (miR‐592) in heart development and CHD with the involvement of KCTD10 and Notch signaling pathway in a CHD mouse model. Cardiac tissues were extracted from CHD and normal mice. Immunohistochemistry staining was performed to detect positive expression rate of KCTD10. A series of inhibitor, activators, and siRNAs was introduced to verified regulatory functions for miR‐592 governing KCTD10 in CHD. Furthermore, the effect of miR‐592 on cell proliferation and apoptosis was also investigated. Downregulated positive rate of KCTD10 was observed in CHD mice. Downregulation of miR‐592 would upregulate expression of KCTD10 and inhibit the activation of Notch signaling pathway, thus promote cell proliferation. This study demonstrates that downregulation of miR‐592 prevents CHD and hypoplastic heart by inhibition of the Notch signaling pathway via negatively binding to KCTD10.
Retracted: MicroRNA‐99b suppresses human cervical cancer cell activity by inhibiting the PI3K/AKT/mTOR signaling pathway
Authors: Li Yong‐Jie , Wang Yue , Wang Yi‐Ying 
Published: November 2018

AbstractCervical cancer is common cancer among women with high morbidity. MicroRNAs (miRs) are involved in the progression and development of cervical cancer. This study aimed to explore the effect of miR‐99b‐5p (miR‐99b) on invasion and migration in cervical cancer through the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway. The microarray‐based analysis was used to screen out differentially expressed miRNAs. Expression of miR‐99b, PI3K, AKT, mTOR, and ribosomal protein S6 kinase (p70S6K) was determined in both cervical cancer tissues and paracancerous tissues. Next, alteration of miR‐99b expression in cervical cancer was conducted to evaluate levels of PI3K, AKT, mTOR, p70S6K matrix metallopeptidase 2, epithelial cell adhesion molecule, and intercellular adhesion molecule 1, as well as the effect of miR‐99b on cell proliferation, invasion, migration, cell cycle distribution, and apoptosis. The results demonstrated that miR‐99b expression was decreased and levels of PI3K, AKT, mTOR, and p70S6K were elevated in cervical cancer tissues. More important, overexpressed miR‐99b repressed the PI3K/AKT/mTOR signaling pathway, inhibited cell proliferation, invasion, and migration, blocked cell cycle entry, and promoted apoptosis in cervical cancer. These results indicate that miR‐99b attenuates the migration and invasion of human cervical cancer cells through downregulation of the PI3K/AKT/mTOR signaling pathway, which provides a therapeutic approach for cervical cancer treatment.
Identification of hsa‐mir‐34a, hsa‐mir‐124, and hsa‐mir‐204 as signatures for cataract
Authors: Wei Ying‐Li , Sun Hao 
Published: November 2018

AbstractCataract, one of the common age‐related diseases that remains the leading cause of blindness worldwide. There have been studies pertaining to microRNA (miRNA) effects on cataract pathogenesis. However, the results were different from each other due to the influence of sequencing platform, sample selection, filter conditions, and so on. This study aims to explore the key miRNAs underlying the pathogenesis of cataract and find prevention and treatment methods. First, six representative cataract miRNA datasets are selected and the key miRNAs are determined. The target genes of these key miRNAs are predicted using the TargetScan software, and then, the functional enrichment and transcription factor binding analysis of these target genes are completed, respectively. Three signature miRNAs associated with cataract are finally identified. Among them, hsa‐mir‐34a seems to be significantly upregulated, while hsa‐mir‐124 and hsa‐mir‐204 are significantly downregulated. The target genes of the signature miRNAs are mainly enriched in hsa04015:Rap1 signaling pathway, hsa04142:lysosome, and hsa04360:axon guidance, indicating that these pathways may be the crucial metabolic pathways. To summarize, three key miRNAs related to cataract pathogenesis are identified, and the corresponding target genes and transcription factors are also analyzed. Moreover, the potential functions of the target genes are revealed. The results of this study may contribute to the targeted therapy of cataract through miRNAs.