scholarly journals MiR-203 Targets to the 3′-UTR of SLUG to Suppress Cerebral Infarction-Induced Endothelial Cell Growth and Motility

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Yunsong Li ◽  
Wei Bi ◽  
Bing Han ◽  
Tao Yuan ◽  
Long Shi ◽  
...  
Keyword(s):  
Cerebral Infarction ◽  
Molecular Mechanisms ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Critical Role ◽  
Ectopic Expression ◽  
Serum Samples ◽  
Invasion And Migration ◽  
And Migration

Cerebral infarction is one of the leading causes of death worldwide, in which angiogenesis plays a critical role. On the other hand, accumulating evidence has demonstrated that microRNAs (miRNAs) function as key modulators in the formation and progression of cerebral infarction. However, the molecular mechanisms of miRNAs underlying cerebral infarction-associated angiogenesis remain unclear. In the present study, we indicated that the expression of miR-203 was significantly downregulated in serum samples derived from patients with cerebral infarction and in mice brain samples following middle cerebral artery occlusion (MCAO) compared with healthy controls. In vitro, the expression of miR-203 was obviously downregulated in hypoxia-induced human umbilical vein vascular endothelial cells (HUVECs). Functionally, ectopic expression of miR-203 drastically suppressed HUVEC proliferation, invasion, and migration. In addition, SLUG, a zinc finger transcriptional repressor, was identified as a direct target of miR-203 and was negatively correlated with miR-203 expression in MCAO mice and in hypoxia-induced HUVECs. Furthermore, overexpression of SLUG reversed the inhibitory effect of miR-203 on proliferation, invasion, and migration abilities of HUVECs. Taken together, our research provides a novel insight of the miR-203-SLUG axis into cerebral infarction-associated endothelial behaviors and may offer a powerful therapeutic target of cerebral ischemia.

Knockdown CYP2S1 inhibits lung cancer cells proliferation and migration

2021 ◽  
pp. 1-9
Author(s):  
Huan Guo ◽  
Baozhen Zeng ◽  
Liqiong Wang ◽  
Chunlei Ge ◽  
Xianglin Zuo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Lung Cancer Cells ◽  
Invasion And Migration ◽  
And Migration

BACKGROUND: The incidence of lung cancer in Yunnan area ranks firstly in the world and underlying molecular mechanisms of lung cancer in Yunnan region are still unclear. We screened a novel potential oncogene CYP2S1 used mRNA microassay and bioinformation database. The function of CYP2S1 in lung cancer has not been reported. OBJECTIVE: To investigate the functions of CYP2S1 in lung cancer. METHODS: Immunohistochemistry and Real-time PCR were used to verify the expression of CYP2S1. Colony formation and Transwell assays were used to determine cell proliferation, invasion and migration. Xenograft assays were used to detected cell growth in vivo. RESULTS: CYP2S1 is significantly up-regulated in lung cancer tissues and cells. Knockdown CYP2S1 in lung cancer cells resulted in decrease cell proliferation, invasion and migration in vitro. Animal experiments showed downregulation of CYP2S1 inhibited lung cancer cell growth in vivo. GSEA analysis suggested that CYP2S1 played functions by regulating E2F targets and G2M checkpoint pathway which involved in cell cycle. Kaplan-Meier analysis indicated that patients with high CYP2S1 had markedly shorter event overall survival (OS) time. CONCLUSIONS: Our data demonstrate that CYP2S1 exerts tumor suppressor function in lung cancer. The high expression of CYP2S1 is an unfavorable prognostic marker for patient survival.

scholarly journals Long noncoding RNA LINC01111 suppresses pancreatic cancer aggressiveness by regulating DUSP1 expression via microRNA-3924

2019 ◽  
Vol 10 (12) ◽  
Author(s):  
Shutao Pan ◽  
Ming Shen ◽  
Min Zhou ◽  
Xiuhui Shi ◽  
Ruizhi He ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cell Invasion ◽  
Molecular Mechanisms ◽  
Invasion And Migration ◽  
Cancer Aggressiveness ◽  
And Migration

AbstractDysfunction in long noncoding RNAs (lncRNAs) is reported to participate in the initiation and progression of human cancer; however, the biological functions and molecular mechanisms through which lncRNAs affect pancreatic cancer (PC) are largely unknown. Here, we report a novel lncRNA, LINC01111, that is clearly downregulated in PC tissues and plasma of PC patients and acts as a tumor suppressor. We found that the LINC01111 level was negatively correlated with the TNM stage but positively correlated with the survival of PC patients. The overexpression of LINC01111 significantly inhibited cell proliferation, the cell cycle, and cell invasion and migration in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, the knockdown of LINC01111 enhanced cell proliferation, the cell cycle, and cell invasion and migration in vitro, as well as tumorigenesis and metastasis in vivo. Furthermore, we found that high expression levels of LINC01111 upregulated DUSP1 levels by sequestering miR-3924, resulting in the blockage of SAPK phosphorylation and the inactivation of the SAPK/JNK signaling pathway in PC cells and thus inhibiting PC aggressiveness. Overall, these data reveal that LINC01111 is a potential diagnostic biomarker for PC patients, and the newly identified LINC01111/miR-3924/DUSP1 axis can modulate PC initiation and development.

scholarly journals Up-Regulation of VCAN Promotes the Proliferation, Invasion and Migration of HCC and Serves as a Biomarker

2021 ◽  
Author(s):  
Sun Guangshun ◽  
Wubin Zheng ◽  
Lan Li ◽  
Liangliang Wu ◽  
Guoqiang Sun ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Dna Methyltransferase ◽  
Molecular Mechanisms ◽  
Gene Knockout ◽  
Treatment Strategies ◽  
Distant Recurrence ◽  
Invasion And Migration ◽  
Dna Methyltransferase Inhibitors ◽  
And Migration

Abstract Hepatocellular carcinoma(HCC) is the world's most common cause of cancer death. Therefore, more molecular mechanisms need to be clarified to meet the urgent need to develop new detection and treatment strategies. We selected three liver cancer transcriptome database GSE124535, GSE136247, GSE144269, and analyze the overexpressed genes contained in them. The overlapping genes were found by Venn map, and two interacting networks module, were found by Mcode. Module1 is mainly related to mitosis and cell cycle, and module2 is mainly related to EMT, angiogenesis, glycolysis and so on. We found that the seed gene in module2 is VCAN. The purpose of this study is to study the expression characteristics of VCAN gene in HCC, and to explore its role in the occurrence and development of HCC and its possible mechanism. Data from TCGAportal shows that compared with normal tissues, the expression of VCAN is up-regulated in HCC tissues. The patients with high expression of VCAN had shorter distant recurrence-free survival and overall survival. The effects of VCAN expression on cell proliferation, invasion and migration were evaluated in vitro by using gene knockout and overexpression strategies. Multiple possible VCAN interactions have also been identified. These result reveal that the level of VCAN is higher in the subtypes of HCC with higher malignant degree and is connected to the poor prognosis. In addition, the treatment of VCAN with DNA methyltransferase inhibitors and transcription factor inhibitors may improve prognosis of patients with liver cancer.

High urokinase expression contributes to the angiogenic properties of endothelial cells derived from circulating progenitors

2006 ◽  
Vol 95 (04) ◽  
pp. 678-688 ◽  
Author(s):  
Agnès Basire ◽  
Florence Sabatier ◽  
Sophie Ravet ◽  
Edouard Lamy ◽  
Agnès Mialhe ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Molecular Mechanisms ◽  
Culture Media ◽  
Umbilical Vein ◽  
Critical Role ◽  
Tube Formation ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Umbilical Vein Endothelial Cells

SummaryEndothelial progenitor cells (EPC) displaya unique ability to repair vascular injury and promote neovascularization although the underlying molecular mechanisms remain poorly understood. Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play a critical role in cell migration and angiogenesis by facilitating proteolysis of extracellular matrix.The aim of the present study was to characterize the uPA/uPAR-dependent proteolytic potential of EPC outgrown from human umbilical cord blood and to analyze its contribution to their angiogenic properties in vitro. Cells derived from EPC (EPDC), presenting typical features of late outgrowth endothelial cells, were compared to mature endothelial cells, represented by human umbilical vein endothelial cells (HUVEC). Using quantitative flow cytometry, enzyme-linked immunosorbent assays and zymography, we demonstrated that EPDC displayed higher levels of uPA and uPAR. In conditioned culture media, uPA-dependant proteolytic activity was also found to be significantly increased in EPDC.This activity was paralleled bya higher secretion of pro-metalloproteinase-2 (pro-MMP-2). Inhibition of EPDC-associated uPA by monoclonal antibodies that block either uPA activity or receptor binding, significantly reduced proliferation, migration and capillary like tube formation. Moreover, tumor necrosis factoralpha and vascular endothelial growth factor,known to be locally secreted in ischemic areas, further increased the proteolytic potential of EPDC by up-regulating uPA and uPAR expression respectively.The EPDC response to these factors was found to be more pronounced than that of HUVEC. In conclusion, these findings indicated that EPDC are characterized by high intrinsic uPA/uPAR-dependent proteolytic potential that could contribute to their invasive and angiogenic behaviour.

Anti-Myeloma Effects of a Novel Synthetic Retinoid Am80 (Tamibarotene) through Inhibition of Angiogenesis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5126-5126
Author(s):  
Takaomi Sanda ◽  
Shinsuke Iida ◽  
Takashi Kuwano ◽  
Mayumi Ono ◽  
Ryuzo Ueda
Keyword(s):  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Myeloma Cell ◽  
Inhibitory Effect ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Myeloma Cells ◽  
Synthetic Retinoid ◽  
And Migration

Abstract In multiple myeloma (MM), the interaction between myeloma cells and bone marrow microenvironment has an important role in the pathogenesis of MM. We first examined the inducing effect of myeloma cells on migration of human umbilical vein vascular endothelial cells (HUVECs). Myeloma cell lines produced varying amounts of vascular endothelial growth factor (VEGF), and migration of HUVECs was induced by co-culture with myeloma cells. We next examined the inhibitory effect of a novel synthetic retinoid Am80 (Tamibarotene) on both myeloma cells and HUVECs. Am80 remarkably inhibited the growth of HUVECs stimulated by VEGF and blocked migration of HUVECs by co-cultured myeloma cells. In addition, VEGF-induced formation of tube-like structures in vitro and neovascularization in mouse corneas were significantly inhibited by Am80. Am80 downregulated both interleukin-6 (IL-6) and IL-6 receptor, and blocked VEGF-induced phosphorylation of VEGF receptor. Furthermore, microarray analysis suggested that Am80 has immunomodulatory effects on myeloma cells. These findings demonstrate that Am80 might be a useful therapeutic agent against MM.

scholarly journals The MYEOV-MYC association promotes oncogenic miR-17/93-5p expression in pancreatic ductal adenocarcinoma

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Hongzhang Shen ◽  
Fuqiang Ye ◽  
Dongchao Xu ◽  
Liangliang Fang ◽  
Xiaofeng Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Ductal Adenocarcinoma ◽  
Invasion And Migration ◽  
And Migration

AbstractPancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy worldwide. As metastasis and malignant progression are primarily responsible for the poor clinical outcomes of PDAC, identifying key genes involved in these processes and the underlying molecular mechanisms of PDAC is vital. In this study, by analyzing TCGA PDAC data and matched GTEx data, we found that MYEOV expression is associated with poor survival in PDAC patients and higher in carcinoma tissues than in healthy tissues. Elevated levels of MYEOV led to enhanced cell proliferation, invasion and migration in vitro and in vivo. Transcriptome analysis results revealed that MYEOV mediates global alterations in gene expression profiles in PDAC cells. MiRNA-seq analysis showed that MYEOV regulates the expression levels of miR-17-5p and miR-93-5p, and its depletion resulted in reduced cell proliferation, invasion and migration, as observed in MYEOV-knockdown PDAC cells. These effects are likely due to the ability of MYEOV to regulate enrichment of the transcription factor MYC at the gene promoter regions of the two miRNAs. Furthermore, we identified a complex containing MYEOV and MYC in the nucleus, providing additional evidence for the association of MYEOV with MYC. Taken together, our results suggest that MYEOV promotes oncogenic miR-17/93-5p expression by associating with MYC, contributing to PDAC progression.

Wnt/beta-catenin and PI3K/Akt/mTOR Signaling Pathways in Glioblastoma: Two Main Targets for Drug Design: A Review

2020 ◽  
Vol 26 (15) ◽  
pp. 1729-1741 ◽  
Author(s):  
Seyed H. Shahcheraghi ◽  
Venant Tchokonte-Nana ◽  
Marzieh Lotfi ◽  
Malihe Lotfi ◽  
Ahmad Ghorbani ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Chemotherapy Resistance ◽  
Wnt Signaling Pathway ◽  
Therapeutic Interventions ◽  
Beta Catenin ◽  
Clinical Prognosis ◽  
Invasion And Migration ◽  
And Migration

: Glioblastoma (GBM) is the most common and malignant astrocytic glioma, accounting for about 90% of all brain tumors with poor prognosis. Despite recent advances in understanding molecular mechanisms of oncogenesis and the improved neuroimaging technologies, surgery, and adjuvant treatments, the clinical prognosis of patients with GBM remains persistently unfavorable. The signaling pathways and the regulation of growth factors of glioblastoma cells are very abnormal. The various signaling pathways have been suggested to be involved in cellular proliferation, invasion, and glioma metastasis. The Wnt signaling pathway with its pleiotropic functions in neurogenesis and stem cell proliferation is implicated in various human cancers, including glioma. In addition, the PI3K/Akt/mTOR pathway is closely related to growth, metabolism, survival, angiogenesis, autophagy, and chemotherapy resistance of GBM. Understanding the mechanisms of GBM’s invasion, represented by invasion and migration, is an important tool in designing effective therapeutic interventions. This review will investigate two main signaling pathways in GBM: PI3K/Akt/mTOR and Wnt/beta-catenin signaling pathways.

Effects and Mechanisms of Anlotinib and Dihydroartemisinin Combination Therapy in Ameliorating Malignant Biological Behavior of Gastric Cancer Cells

2020 ◽  
Vol 21 ◽  
Author(s):  
Qiong Luo ◽  
Suyun Zhang ◽  
Donghuan Zhang ◽  
Rui Feng ◽  
Nan Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Chorioallantoic Membrane ◽  
Cell Counting ◽  
Biological Behavior ◽  
Gastric Cancer Cells ◽  
Invasion And Migration ◽  
Apoptosis Related Protein ◽  
And Migration

Background: Gastric cancer(GC) is currently one of the major malignancies that threatens human lives and health. Anlotinib is a novel small-molecule that inhibits angiogenesis to exert anti-tumor effects. However, the function in gastric cancer is incompletely understood. Objective: The aim of the present study was to investigate the anti-tumor effects and molecular mechanisms of anlotinib combined with dihydroartemisinin (DHA) in SGC7901 gastric cancer cells. Method: Different concentrations of anlotinib and DHA were used to treat SGC7901 gastric cancer cells, after which cell proliferation was measured. Drug interactions of anlotinib and DHA were analyzed by the Chou-Talalay method with CompuSyn software. proliferation, apoptosis, invasion, migration, and angiogenesis were measured using the cell counting kit-8 (CCK8) assay, flow cytometry, Transwell invasion assays, scratch assays, and chicken chorioallantoic membrane (CAM) assays. proliferation-associated protein (Ki67), apoptosis-related protein (Bcl-2), and vascular endothelial growth factor A (VEGF-A) were quantified by Western bloting. Results: The combination of 2.5 μmol/L of anlotinib and 5 of μmol/L DHA was highly synergistic in inhibiting cell growth, significantly increased the apoptosis rate and suppressed obviously the invasion and migration capability and angiogenesis of gastric cancer cells. In addition, the expression levels of Ki67, Bcl-2, and VEGF-A, as well as angiogenesis, were significantly decreased in the Combination of drugs compared with in control and either drug alone. Conclusion: The combination of anlotinib and DHA showed synergistic antitumor activity, suggesting their potential in treating patients with gastric cancer.

scholarly journals Cyr61 promotes Schwann cell proliferation and migration via αvβ3 integrin

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhenghui Cheng ◽  
Yawen Zhang ◽  
Yinchao Tian ◽  
Yuhan Chen ◽  
Fei Ding ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Peripheral Nerves ◽  
Molecular Mechanisms ◽  
Αvβ3 Integrin ◽  
Promoting Effect ◽  
Ccn Family ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Schwann cells (SCs) play a crucial role in the repair of peripheral nerves. This is due to their ability to proliferate, migrate, and provide trophic support to axon regrowth. During peripheral nerve injury, SCs de-differentiate and reprogram to gain the ability to repair nerves. Cysteine-rich 61 (Cyr61/CCN1) is a member of the CCN family of matrix cell proteins and have been reported to be abundant in the secretome of repair mediating SCs. In this study we investigate the function of Cyr61 in SCs. Results We observed Cyr61 was expressed both in vivo and in vitro. The promoting effect of Cyr61 on SC proliferation and migration was through autocrine and paracrine mechanisms. SCs expressed αvβ3 integrin and the effect of Cyr61 on SC proliferation and migration could be blocked via αvβ3 integrin. Cyr61 could influence c-Jun protein expression in cultured SCs. Conclusions In this study, we found that Cyr61 promotes SC proliferation and migration via αvβ3 integrin and regulates c-Jun expression. Our study contributes to the understanding of cellular and molecular mechanisms underlying SC’s function during nerve injury, and thus, may facilitate the regeneration of peripheral nerves after injury.

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