bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpression of miR‐301a‐3p promotes colorectal cancer cell proliferation and metastasis by targeting deleted in liver cancer‐1 and runt‐related transcription factor 3
Authors: Zhang Liuliu , Zhang Yi , Zhu Huayun , Sun Xiaofeng , Wang Xiaohua , Wu Pingping , Xu Xinyu 
Published: October 2018

AbstractColorectal cancer (CRC) is the third most common type of cancer. MicroRNAs have been reported to participate in the progression of various cancers. In previous studies, miR‐301a‐3p expression was shown to be upregulated in CRC tissues. However, the underlying mechanism of miR‐301a‐3p in CRC has not yet been elucidated. Herein, the level of miR‐301a‐3p was found to be significantly upregulated in CRC clinical tissues and cell lines (HT29 and SW620). In addition, overexpression of miR‐301a‐3p obviously promoted cell proliferation, migration and invasion, and inhibited cell apoptosis in CRC cells. Meanwhile, upregulated miR‐301a‐3p expression also enhanced the expressions of Bax, caspase‐3, caspase‐9, matrix metalloproteinase (MMP)‐2, and MMP‐9, while the expression of Bax‐2 was decreased. Furthermore, deleted in liver cancer‐1 (DLC‐1) and runt‐related transcription factor 3 (RUNX3) were verified to be direct target genes of miR‐301a‐3p. Furthermore, overexpression of DLC‐1 and RUNX3 revealed antitumor effects in CRC cell lines with the inhibition of cell proliferation, migration and invasion, and the induction of cell apoptosis. In addition, the expressions of Bax, caspase‐3, caspase‐3, MMP‐2, and MMP‐9 could be decreased after upregulating the expressions of DLC‐1 and RUNX3, along with the upregulation of Bax‐2. Moreover, overexpression of miR‐301a‐3p could promote the growth of xenograft tumors and liver metastasis in vivo, along with reducing the expressions of DLC‐1 and RUNX3. Overall, miR‐301a‐3p might act as a tumor inducer in CRC cells through negatively regulating DLC‐1 and RUNX3.
MALAT1 promoted cell proliferation and migration via MALAT1/miR‐155/MEF2A pathway in hypoxia of cardiac stem cells
Authors: Wang Qiuyun , Lu Guoping , Chen Zhenyue 
Published: October 2018

AbstractAccumulating evidence revealed that hypoxia contributed to many human diseases, including ischemic myocardium and heart failure (HF). In recent years, the roles of hypoxia in stem cell survival and cardiac biology have been studied extensively. However, the underlying molecular mechanisms remain to be elucidated. As a leading cause of HF, ischemic heart disease was correlated with hypoxia. In this study, we firstly constructed the hypoxia cell model by CoCl2 in cardiac stem cells (CSCs) and found that hypoxia induced the cell proliferation and migration potential in CSCs. Then, we demonstrated that the expression of metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) was promoted in CoCl2‐induced CSCs hypoxia model. Furthermore, we found that knockdown of MALAT1 inhibited the cell proliferation and migration in CoCl2‐induced CSCs hypoxia model. In addition, we revealed that MALAT1 regulated the microRNA‐155 (miR‐155) expression in CSCs under both the normal and hypoxia conditions and further, manipulation of the miR‐155 expression affected the role of MALAT1 in CoCl2‐induced CSCs hypoxia cell model. We then illustrated that miR‐155 regulated the myocyte enhancer factor 2A (MEF2A) expression in CSCs under both the normal and hypoxia conditions and further, changing the expression of MEF2A affected the role of miR‐155. Finally, we demonstrated that MALAT1 regulated the MEF2A expression and exerted its role via modulation of the MALAT1/miR‐155/MEF2A pathway. Taken together, our study illustrated that MALAT1 promoted the cell proliferation and migration in CoCl2‐induced CSCs hypoxia model, acting mechanistically by promoting MEF2A expression via “sponging” miR‐155.
Network pharmacology‐based prediction of the active ingredients, potential targets, and signaling pathways in compound Lian‐Ge granules for treatment of diabetes
Authors: Xue Jintao , Shi Yongli , Li Chunyan , Song Huijie 
Published: October 2018

AbstractAimsCompound Lian‐Ge granules (CLGGs) is a traditional Chinese medicine preparation with good hypoglycemic effect and health function. This study was to predict its active ingredients, potential targets, signaling pathways, and investigate its mechanism of “ingredient‐targets‐pathways.”MethodsPharmacodynamics studies on diabetic rats showed that CLGGs had an obvious hypoglycemic effect. On this basis, 27 hypoglycemic active ingredients were screened out. Their targets were confirmed by comparing with these hypoglycemic targets in PharmMapper and DrugBank databases via reversed pharmacophore matching approach. The relationships between ingredients and targets were revealed by comparing data in the String database. A network of “ingredient‐target‐passageway” was constructed.ResultsStudies showed that CLGGs had 24 active ingredients, ie, berberine, puerarin, danshinolic acid A, and sinigrin, etc. These ingredients involved nine targets, ie, insulin‐like growth factor 1 receptor, insulin‐degrading enzyme, ɑ‐amylase, and so on, and 111 metabolic pathways, eg, hypoxia‐inducible factor 1 signaling pathway, PI3K‐Akt signaling pathway, mammalian target of rapamycin signaling pathway, and FoxO signaling pathway.ConclusionUsing network pharmacology methods, this study predicted the hypoglycemic active ingredients in CLGGs and revealed their targets, and provided a clue for further exploration of the hypoglycemic mechanism of CLGGs.
Synergistic effect of extracellularly supplemented osteopontin and osteocalcin on stem cell proliferation, osteogenic differentiation, and angiogenic properties
Authors: Carvalho Marta S , Cabral Joaquim MS , da Silva Cláudia L , Vashishth Deepak 
Published: October 2018

AbstractA high demand for functional bone grafts is being observed worldwide, especially due to the increased life expectancy. Osteoinductive components should be incorporated into functional bone grafts, accelerating cell recruitment, cell proliferation, angiogenesis, and new bone formation at a defect site. Noncollagenous bone matrix proteins, especially osteopontin (OPN) and osteocalcin (OC), have been reported to regulate some physiological process, such as cell migration and bone mineralization. However, the effects of OPN and OC on cell proliferation, osteogenic differentiation, mineralization, and angiogenesis are still undefined. Therefore, we assessed the exogenous effect of OPN and OC supplementation on human bone marrow mesenchymal stem/stromal cells (hBM MSC) proliferation and osteogenic differentiation. OPN dose‐dependently increased the proliferation of hBM MSC, as well as improved the angiogenic properties of human umbilical vein endothelial cells (HUVEC) by increasing the capillary‐like tube formation in vitro. On the other hand, OC enhanced the differentiation of hBM MSC into osteoblasts and demonstrated an increase in extracellular calcium levels and alkaline phosphatase activity, as well as higher messenger RNA levels of mature osteogenic markers osteopontin and osteocalcin. In vivo assessment of OC/OPN‐enhanced scaffolds in a critical‐sized defect rabbit long‐bone model revealed no infection, while new bone was being formed. Taken together, these results suggest that OC and OPN stimulate bone regeneration by inducing stem cell proliferation, osteogenesis and by enhancing angiogenic properties. The synergistic effect of OC and OPN observed in this study can be applied as an attractive strategy for bone regeneration therapeutics by targeting different vital cellular processes.
RELA/NEAT1/miR‐302a‐3p/RELA feedback loop modulates pancreatic ductal adenocarcinoma cell proliferation and migration
Authors: Luo Zhen , Yi Zhong‐Jie , Ou Zheng‐Lin , Han Tong , Wan Tao , Tang Yong‐Chang , Wang Zhi‐Chao , Huang Fei‐Zhou 
Published: October 2018

AbstractPancreatic ductal adenocarcinoma (PDAC) remains a challenging malignancy due to distant metastasis. RELA, a major component of the NF‐κB pathway, could serve as an oncogene through activating proliferation or migration‐related gene expression, including NEAT1, a well‐known oncogenic long noncoding RNA. In the current study, the expression and function of RELA and NEAT1 in PDAC were examined. The potential upstream regulatory microRNAs of RELA were screened and verified for their correlation with RELA and NEAT1. The expression and function of the selected miR‐302a‐3p were evaluated. RELA and NEAT1 expression were upregulated in PDAC tissues, particularly in PDAC tissues with lymph node metastasis, and their expression correlated with clinical parameters. RELA overexpression promoted PDAC cell proliferation and migration, which could be partially attenuated by the NEAT1 knockdown. By binding to RELA, miR‐302a‐3p inhibited RELA expression, as well as PDAC cell proliferation and migration. RELA downstream NEAT1 expression was negatively regulated by miR‐302a‐3p; the suppressive effect of NEAT1 knockdown on PDAC cell proliferation and migration was partially attenuated by miR‐302a‐3p inhibition. Moreover, through direct binding, the expression of miR‐302a‐3p was also negatively regulated by NEAT1. The expression of miR‐302a‐3p was downregulated and negatively correlated with RELA or NEAT1 in tissue samples, indicating that rescuing miR‐302a‐3p expression may inhibit PDAC cell proliferation and migration through RELA/NEAT1. In summary, RELA, NEAT1, and miR‐302a‐3p form a feedback loop in PDAC to modulate PDAC cell proliferation and migration.
A randomized clinical trial on the antitumoral effects of low molecular weight heparin in the treatment of esophageal cancer
Authors: Taghizadeh Kermani Ali , Hosseini Sare , Fanipakdel Azar , Joudi Mashhad Mona , Akhavan Rezayat Kambiz , Zardadi Mahdi , Gholami Arezoo , Javadinia Seyed Alireza , Ferns Gordon A. , Avan Amir 
Published: October 2018

AbstractThe current treatment approaches for esophageal cancer are associated with poor survival, and there are ongoing efforts to find new and more effective therapeutic strategies. There are several reports on the antitumoral effects of low‐molecular‐weight heparins (LMWHs). We have assessed the possible survival benefit of LMWHs in esophageal malignancies. This was a randomized, single‐blind, multicenter, Phase II clinical trial on nonmetastatic esophageal cancer candidate for neoadjuvant chemoradiotherapy. Patients were randomly assigned to the chemoradiotherapy‐only arm or chemoradiotherapy plus enoxaparin arm using 1:1 allocation. Radiotherapy was delivered in 1.8‐Gy daily fractions to a dose of 50.4 Gy in both groups. Paclitaxel 50 mg/m2 and carboplatin (AUC 2) were administered weekly, concurrent with radiotherapy. In the intervention group, patients received enoxaparin (40 mg) and chemoradiation daily. 4–6 weeks after treatment, all patients underwent esophagectomy. After a median follow up of 7 months, estimated 1 year disease‐free survival (DFS) in the intervention group was 78.9% and was 70% in the control groups (
p = 0.5). Toxicity from the experimental treatment was minimal, and there were no treatment‐related deaths. A pathologically complete response in intervention and control group was 64.8% and 62.5%, respectively (
p = 0.9). There was a nonsignificant trend toward improved survival by the addition of enoxaparin to the concurrent chemoradiotherapy regimen. However, 1 y DFS of both groups were high as expected. A longer follow‐up and a larger sample size are required.
Effect of mesenchymal stem cells‐derived exosomes on tumor microenvironment: Tumor progression versus tumor suppression
Authors: Shojaei Samaneh , Hashemi Seyed Mahmoud , Ghanbarian Hossein , Salehi Mohammad , Mohammadi‐Yeganeh Samira 
Published: October 2018

AbstractMesenchymal stem cells (MSCs) are multipotent cells with the potential to differentiate into different cell types. Owing to their immunosuppressive and anti‐inflammatory properties, they are widely used in regenerative medicine, but they have a dual effect on cancer progression and exert both growth‐stimulatory or ‐inhibitory effects on different cancer types. It has been proposed that these controversial effects of MSC in tumor microenvironment (TME) are mediated by their polarization to proinflammatory or anti‐inflammatory phenotype. In addition, they can polarize the immune system cells that in turn influence tumor progression. One of the mechanisms involved in the TME communications is extracellular vesicles (EVs). MSCs, as one of cell populations in TME, produce a large amount of EVs that can influence tumor development. Similar to MSC, MSC‐EVs can exert both anti‐ or protumorigenic effects. In the current study, we will investigate the current knowledge related to MSC role in cancer progression with a focus on the MSC‐EV content in limiting tumor growth, angiogenesis, and metastasis. We suppose MSC‐EVs can be used as safe vehicles for delivering antitumor agents to TME.
Identification of LINC01234 and MIR210HG as novel prognostic signature for colorectal adenocarcinoma
Authors: He Zhiyun , Dang Jie , Song Ailin , Cui Xiang , Ma Zhijun , Zhang Zhongtao 
Published: October 2018

AbstractThis study aimed to identify potential biomarkers and the therapeutic targets for colorectal adenocarcinoma by systematically evaluate a large scale of long noncoding RNAs (lncRNAs) expression data from TCGA. The algorithm t‐distributed stochastic neighbor embedding and hierarchical clustering were utilized to group the samples into three clusters that showed a different prognosis. To identify the relationship between the clustered groups and different histoclinical features, different statistical methods were used. The functions of LINC01234 and MIR210HG were investigated with the help of the public database. The results showed that the expression levels of lncRNAs were able to distinguish the tumor samples from the normal tissues and in further they were able to predict the prognosis of the patients. We proposed two potential lncRNAs, which might serve as a biomarker or therapeutic targets. LINC01234 can be a good biomarker. In contrast, MIR210HG participated in the progression of colorectal adenocarcinoma by regulating hypoxia. It might function through an lncRNA–microRNA–messenger RNA regulatory network with MIR210 and RASSF7.
Transcriptional landscape of alternative splicing during peripheral nerve injury
Authors: Zhao Lili , Yi Sheng 
Published: October 2018

AbstarctAlternative splicing (AS) regulates a variety of biological activities in numerous tissues and organs, including the nervous system. However, the existence and specific roles of AS events during peripheral nerve repair and regeneration remain largely undetermined. In the current study, by mapping splice‐crossing sequence reads, we identified AS events and relevant spliced genes in rat sciatic nerve stumps following sciatic nerve crush. AS‐related genes at 1, 4, 7, and 14 days post nerve crush were compared with those at 0 day to discover alternatively spliced genes induced by sciatic nerve crush. These injury‐induced alternatively spliced genes were then categorized to diseases and biological functions, genetic networks, and canonical signaling pathways. Bioinformatic analysis indicated that these alternatively spliced genes were mainly correlated to immune response, cellular growth, and cellular function maintenance. Our study elucidated AS events following peripheral nerve injury and might help deepen our understanding of the molecular mechanisms underlying peripheral nerve regeneration.
Apoptosis in HepaRG and HL‐7702 cells inducted by polyphyllin II through caspases activation and cell‐cycle arrest
Authors: Wang Wenping , Dong Xiaoxv , You Longtai , Sai Na , Leng Xin , Yang Chunjing , Yin Xingbin , Ni Jian 
Published: October 2018

AbstractRhizoma Paridis, a traditional Chinese medicine, has shown promise in cancer prevention and therapy. Polyphyllin II is one of the most significant saponins in Rhizoma Paridis and it has toxic effects on kinds of cancer cells. However, our results in this study proved that the polyphyllin II has hepatotoxicity in vitro through caspases activation and cell‐cycle arrest. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide results indicated polyphyllin II inhibited proliferation, induced apoptosis in HepaRG cells and HL‐7702 cells and showed a concentration and time‐dependent. Then, we selected the innovative cell model‐HepaRG cells to explore the mechanism of hepatotoxicity. Our data showed the reactive oxygen species (ROS) increased and the mitochondrial membrane potential decreased in HepaRG cells after administration of polyphyllin II. Besides, with the increase of concentration, the release of lactate dehydrogenase increased and the S phase of the cell cycle was arrested. Nevertheless, when pretreatment with antioxidant N‐acetylcysteine, apoptotic cells decreased significantly, inhibited the production of ROS and improved the decrease of membrane potential in HepaRG cells. Moreover, polyphyllin II treatment increased levels of Fas, Bax, cytochrome
c, activated caspase‐3, ‐8, ‐9, cleaved poly(ADP‐ribose) polymerase and decreased Bcl‐2 expression levels. Finally, we identified two signal pathways of apoptosis induced by polyphyllin II including the death receptor pathway and the mitochondria pathway. This study confirmed the hepatotoxicity of the polyphyllin II in vitro, which has never been discovered and gave a wake‐up call for the clinical application of Rhizoma Paridis.
Tetrandrine, a novel inhibitor of ether‐à‐go‐go‐1 (Eag1), targeted to cervical cancer development
Authors: Wang Xuzhao , Chen Yafei , Li Junwei , Guo Shuai , Lin Xiaoe , Zhang Hailin , Zhan Yong , An Hailong 
Published: October 2018

AbstractMortality‐to‐incidence ratios in patients with cancer are extremely high, positioning cancer as a major cause of death worldwide. Ether‐à‐go‐go‐1 (Eag1) is an ion channel that plays important roles in tumour proliferation, malignant transformation, invasion, metastasis, recurrence, and prognosis. Therefore, identifying potent and specific Eag1 channel inhibitors is crucial. In this study, we identified the first natural inhibitor of Eag1, the traditional Chinese medicine agent tetrandrine, and explored the underlying mechanism. Tetrandrine directly interacted with Eag1 and inhibited the currents in a concentration‐dependent manner (IC50 of 69.97 ± 5.2 μM), and the amino acids Ile
550, Thr
552, and Gln
557 in the Eag1 C‐linker domain were critical for tetrandrine’s inhibitory effect. Moreover, tetrandrine reduced the proliferation of HeLa cells and Chinese hamster ovary (CHO) cells stably expressing Eag1 in a concentration‐dependent manner. Finally, tetrandrine (30 mg/kg/day) inhibited tumor growth in mice, demonstrating a 64.21% inhibitory rate of HeLa cell‐transplanted tumors. These results suggest that tetrandrine is a potent and selective Eag1 channel inhibitor, and could act as a leading compound in the development of therapies for Eag1 ion channel dysfunction‐induced diseases.
DNA methylation regulates α‐smooth muscle actin expression during cardiac fibroblast differentiation
Authors: He Yanru , Ling Sunkai , Sun Yuning , Sheng Zulong , Chen Zhongpu , Pan Xiaodong , Ma Genshan 
Published: October 2018

AbstractCardiac fibroblast (CF) differentiation to myofibroblasts expressing α‐smooth muscle actin (α‐SMA) plays a key role in cardiac fibrosis. Therefore, a study of the mechanism regulating α‐SMA expression is a means to understanding the mechanism of fibroblast differentiation and cardiac fibrosis. Previous studies have shown that DNA methylation is associated with gene expression and is related to the development of tissue fibrosis. However, the mechanisms by which CF differentiation is regulated by DNA methylation remain unclear. Here, we explored the epigenetic regulation of α‐SMA expression and its relevance in CF differentiation. In this study, we demonstrated that α‐SMA was overexpressed and DNMT1 expression was downregulated in the infarct area after myocardial infarction. Treatment of CFs with transforming growth factor‐β1 (TGF‐β1) in vitro upregulated α‐SMA expression via epigenetic modifications. TGF‐β1 also inhibited DNMT1 expression and activity during CF differentiation. In addition, α‐SMA expression was regulated by DNMT1. Conversely, increasing DNMT1 expression levels rescued the TGF‐β1‐induced upregulation of α‐SMA expression. Finally, TGF‐β1 regulated α‐SMA expression by inhibiting the DNMT1‐mediated DNA methylation of the α‐SMA promoter. Taken together, our research showed that inhibition of the DNMT1‐mediated DNA methylation of the α‐SMA promoter plays an essential role in CF differentiation. In addition, DNMT1 may be a new target for the prevention and treatment of myocardial fibrosis.
LncRNA DANCR promotes cervical cancer progression by upregulating ROCK1 via sponging miR‐335‐5p
Authors: Liang Huiling , Zhang Chunyan , Guan Hongya , Liu Jia , Cui Yuanbo 
Published: October 2018

AbstractEmerging evidence highlights the key regulatory roles of long noncoding RNAs (lncRNAs) in the initiation and progression of numerous malignancies. The lncRNA identified as differentiation antagonizing nonprotein coding RNA (DANCR) is a novel lncRNA widely involved in the development of multiple human cancers. However, the function of DANCR and its potential molecular mechanism in cervical cancer remain unclear. In this study, we discovered that DANCR was significantly elevated in cervical cancer tissues and cells, and was closely correlated with poor prognosis of cervical cancer patients. In addition, knockdown of DANCR inhibited proliferation, migration, and invasion of cervical cancer cells in vitro, indicating that DANCR functioned as an oncogene in cervical cancer. Moreover, we verified that DANCR could directly bind to miR‐335‐5p, isolating miR‐335‐5p from its target gene Rho‐associated coiled‐coil containing protein kinase 1 (ROCK1). Functional analysis showed that DANCR regulated ROCK1 expression by competitively binding to miR‐335‐5p. Further cellular behavioral experiments revealed that miR‐335‐5p mimics and ROCK1 knockdown reversed the effects of upregulated DANCR on proliferation, migration, invasion, and epithelial‐mesenchymal transition (EMT) of cervical cancer cells by rescue assays. In summary, this study demonstrated that DANCR promoted cervical cancer progression by functioning as a competing endogenous RNA (ceRNA) to regulate ROCK1 expression via sponging miR‐335‐5p, suggesting a novel potential therapeutic target for cervical cancer.