scholarly journals HIF-1α promoted vasculogenic mimicry formation in lung adenocarcinoma through NRP1 upregulation in the hypoxic tumor microenvironment

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Ran Fu ◽  
Wenwen Du ◽  
Zongli Ding ◽  
Yi Wang ◽  
Yue Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Vasculogenic Mimicry ◽  
Tube Formation ◽  
Luciferase Reporter ◽  
Vimentin Expression ◽  
Cell Metastasis ◽  
Therapeutic Value ◽  
Key Factor ◽  
Important Form

AbstractNeovascularization is a key factor that contributes to tumor metastasis, and vasculogenic mimicry (VM) is an important form of neovascularization found in highly invasive tumors, including lung cancer. Despite the increasing number of studies focusing on VM, the mechanisms underlying VM formation remain unclear. Herein, our study explored the role of the HIF-1α/NRP1 axis in mediating lung adenocarcinoma metastasis and VM formation. HIF-1α, NRP1 expression, and VM in lung adenocarcinoma (LUAD) patient samples were examined by immunohistochemical staining. Quantitative real-time (qRT-PCR), western blot, transwell assay, wound healing assay, and tube formation assay were performed to verify the role of HIF-1α/NRP1 axis in LUAD metastasis and VM formation. ChIP and luciferase reporter assay were used to confirm whether NRP1 is a direct target of HIF-1α. In LUAD tissues, we confirmed a positive relationship between HIF-1α and NRP1 expression. Importantly, high HIF-1α and NRP1 expression and the presence of VM were correlated with poor prognosis. We also found that HIF-1α could induce LUAD cell migration, invasion, and VM formation by regulating NRP1. Moreover, we demonstrated that HIF-1α can directly bind to the NRP1 promoter located between −2009 and −2017 of the promoter. Mechanistically, MMP2, VE-cadherin, and Vimentin expression were affected. HIF-1α plays an important role in inducing lung adenocarcinoma cell metastasis and VM formation via upregulation of NRP1. This study highlights the potential therapeutic value of targeting NRP1 for suppressing lung adenocarcinoma metastasis and progression.

scholarly journals Platelets as Key Factors in Hepatocellular Carcinoma

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1022 ◽  
Author(s):  
Natasa Pavlovic ◽  
Bhavna Rani ◽  
Pär Gerwins ◽  
Femke Heindryckx
Keyword(s):  
Hepatocellular Carcinoma ◽  
Crucial Role ◽  
Primary Liver Cancer ◽  
Organ Damage ◽  
Potential Effect ◽  
Key Factors ◽  
Therapeutic Value ◽  
Key Factor ◽  
Proliferation And Invasion

Hepatocellular carcinoma (HCC) is a primary liver cancer that usually develops in the setting of chronic inflammation and liver damage. The hepatic microenvironment plays a crucial role in the disease development, as players such as hepatic stellate cells, resident liver macrophages (Kupffer cells), endothelial cells, extracellular matrix, and a variety of immune cells interact in highly complex and intertwined signaling pathways. A key factor in these cross-talks are platelets, whose role in cancer has gained growing evidence in recent years. Platelets have been reported to promote HCC cell proliferation and invasion, but their involvement goes beyond the direct effect on tumor cells, as they are known to play a role in pro-fibrinogenic signaling and the hepatic immune response, as well as in mediating interactions between these factors in the stroma. Anti-platelet therapy has been shown to ameliorate liver injury and improve the disease outcome. However, platelets have also been shown to play a crucial role in liver regeneration after organ damage. Therefore, the timing and microenvironmental setting need to be kept in mind when assessing the potential effect and therapeutic value of platelets in the disease progression, while further studies are needed for understanding the role of platelets in patients with HCC.

scholarly journals Long Non-Coding RNA HOXA-AS2 Regulates Malignant Glioma Behaviors and Vasculogenic Mimicry Formation via the MiR-373/EGFR Axis

2017 ◽  
Vol 45 (1) ◽  
pp. 131-147 ◽  
Author(s):  
Yana Gao ◽  
Hai Yu ◽  
Yunhui Liu ◽  
Xiaobai Liu ◽  
Jian Zheng ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Cell Viability ◽  
Malignant Glioma ◽  
Cell Lines ◽  
Vasculogenic Mimicry ◽  
Tube Formation ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Expression And Activity

Background/Aims: Vasculogenic mimicry (VM) has been reported to be a novel glioma neovascularization process. Anti-VM therapy provides new insight into glioma clinical management. In this study, we revealed the role of the long non-coding RNA HOXA cluster antisense RNA 2 (HOXA-AS2) in malignant glioma behaviors and VM formation. Methods: Quantitative real-time PCR was performed to determine the expression levels of HOXA-AS2 in glioma samples and glioblastoma cell lines. CD34-periodic acid-Schiff dual-staining was performed to assess VM in glioma samples. CCK-8, transwell, and Matrigel tube formation assays were performed to measure the effects of HOXA-AS2 knockdown on cell viability, migration, invasion, and VM tube formation, respectively. RNA immunoprecipitation, dual-luciferase reporter and Western blot assays were performed to explore the molecular mechanisms underlying the functions of HOXS-AS2 in glioblastoma cells. A nude mouse xenograft model was used to investigate the role of HOXA-AS2 in xenograft glioma growth and VM density. Student’s t-tests, one-way ANOVAs followed by Bonferroni posthoc tests, and chi-square tests were used for the statistical analyses. Results: HOXA-AS2 was upregulated in glioma samples and cell lines and was positively correlated with VM. HOXA-AS2 knockdown attenuated cell viability, migration, invasion, and VM formation in glioma cells and inhibited the expression of vascular endothelial-cadherin (VE-cadherin), as well as the expression and activity of matrix metalloproteinase matrix metalloproteinase (MMP)-2 and MMP-9. miR-373 was downregulated in glioma samples and cell lines and suppressed malignancy in glioblastoma cells. HOXA-AS2 bound to miR-373 and negatively regulated its expression. Epidermal growth factor receptor (EGFR), a target of miR-373, increased the expression levels of VE-cadherin, as well as the expression and activity levels of MMP-2 and MMP-9, via activating phosphatidylinositol 3-kinase/serine/threonine kinase pathways. HOXA-AS2 knockdown combined with miR-373 overexpression yielded optimal tumor suppressive effects and the lowest VM density in vivo. Conclusion: HOXA-AS2 knockdown inhibited malignant glioma behaviors and VM formation via the miR-373/EGFR axis.

scholarly journals MiR-429 Inhibits the Angiogenesis of Human Brain Microvascular Endothelial Cells through SNAI2-Mediated GSK-3β/β-Catenin Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Yameng Sun ◽  
Shenghao Ding ◽  
Yiling Fan ◽  
Fei Shen ◽  
Qing Dong ◽  
...  
Keyword(s):  
Western Blot ◽  
Cell Model ◽  
Glucose Deprivation ◽  
Tube Formation ◽  
Luciferase Reporter ◽  
Regulation Mechanism ◽  
Oxygen And Glucose Deprivation ◽  
Downstream Target ◽  
Gsk 3Β

MicroRNA (miRNA) dysfunction has been confirmed as a key event of ischemic stroke appearance. This study is aimed at revealing the role of miR-429 in the angiogenesis of HBMECs. The HBMECs were treated with oxygen and glucose deprivation (OGD) to establish the ischemic cell model. The qRT-PCR was used to measure the expression levels of the miR-429 in the serums of the patients or cells, and CCK-8, wound healing assay, and tube formation assay were used to observe the effects of miR-429 on the phenotype of HBMECs. Moreover, the Targetscan, dual-luciferase reporter assay, and Western blot were used to reveal the downstream target and regulation mechanism of miR-429 in OGD-induced HBMECs. The results showed that miR-429 was significantly upregulated in the serums of the patients, and overexpressed miR-429 could extremely inhibit the viability, migration, and tube formation of OGD-induced HBMECs. Furthermore, it was found that SNAI2 was a downstream factor of miR-429, and SNAI2 could rescue the effects of miR-429 on OGD-induced HBMECs. Besides, the Western blot showed that miR-429 could affect the activity of GSK-3β/β-catenin pathway via inhibiting the expression of SNAI2. In conclusion, this study suggests that miR-429 inhibits the angiogenesis of HBMECs through SNAI2-mediated GSK-3β/β-catenin pathway.

scholarly journals Down-regulation of miR-361-5p promotes the viability, migration and tube formation of endothelial progenitor cells via targeting FGF1

2020 ◽  
Vol 40 (10) ◽  
Author(s):  
Xiaofeng Yang ◽  
Yanli Song ◽  
Yuexi Sun ◽  
Mengmeng Wang ◽  
Yang Xiang
Keyword(s):  
Growth Factor ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Tube Formation ◽  
Luciferase Reporter ◽  
Sprague Dawley ◽  
Endothelial Progenitor ◽  
Down Regulation ◽  
Sd Rats

Abstract Transplantion of bone marrow-derived endothelial progenitor cells (EPCs) may be a novel treatment for deep venous thrombosis (DVT). The present study probed into the role of microRNA (miR)-361-5p in EPCs and DVT recanalization. EPCs were isolated from male Sprague–Dawley (SD) rats and identified using confocal microscopy and flow cytometry. The viability, migration and tube formation of EPCs were examined using MTT assay, wound-healing assay and tube formation assay, respectively. Target gene and potential binding sites between miR-361-5p and fibroblast growth factor 1 (FGF1) were predicted by StarBase and confirmed by dual-luciferase reporter assay. Relative expressions of miR-361-5p and FGF1 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed. A DVT model in SD rats was established to investigate the role of EPC with miR-361-5p antagomir in DVT by Hematoxylin–Eosin (H&E) staining. EPC was identified as 87.1% positive for cluster of difference (CD)31, 2.17% positive for CD133, 85.6% positive for von Willebrand factor (vWF) and 94.8% positive for vascular endothelial growth factor receptor-2 (VEGFR2). MiR-361-5p antagomir promoted proliferation, migration and tube formation of EPCs and up-regulated FGF1 expression, thereby dissolving thrombus in the vein of DVT rats. FGF1 was the target of miR-361-5p, and overexpressed FGF1 reversed the effects of up-regulating miR-361-5p on suppressing EPCs. Down-regulation of miR-361-5p enhanced thrombus resolution in vivo and promoted EPC viability, migration and angiogenesis in vitro through targeting FGF1. Therefore, miR-361-5p may be a potential therapeutic target for DVT recanalization.

scholarly journals The novel circular RNA circ-CAMK2A enhances lung adenocarcinoma metastasis by regulating the miR-615-5p/fibronectin 1 pathway

2019 ◽  
Vol 24 (1) ◽  
Author(s):  
Jiahui Du ◽  
Guangzhao Zhang ◽  
Hongli Qiu ◽  
Haifeng Yu ◽  
Wuying Yuan
Keyword(s):  
Lung Adenocarcinoma ◽  
Clinical Stage ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Advanced Clinical Stage ◽  
Reverse Transcription Pcr ◽  
Metastasis Model

Abstract Background Circular RNA (circRNA) has recently been considered as a key regulator in carcinogenesis. In this study, we investigated the functional significance and regulatory role of circ-CAMK2A (hsa_circ_0128332) in lung adenocarcinoma (LUAD). Methods GSE101586 was employed to screen differentially expressed circRNAs. = Relative expression levels of circ-CAMK2A, miR-615-5p, fibronectin 1 (FN1), MMP2, and MMP9 were tested by quantitative reverse transcription PCR (qRT-PCR) or western blotting. Functional experiments were performed by CCK-8, wound healing, and transwell assays. Luciferase reporter and biotin-labeled RNA pull-down assays were carried out to evaluate the interaction between circ-CAMK2A, miR-615-5p, and fibronectin 1. In addition, a lung metastasis model was constructed to determine the metastasis-promoting role of circ-CAMK2A in vivo. Results Circ-CAMK2A overexpression was observed in LUAD and was closely associated with lymph node metastasis, distant metastasis, advanced clinical stage, and poor prognosis. Circ-CAMK2A silencing evidently inhibited LUAD cell migration and invasion, whereas circ-CAMK2A overexpression had an opposite effect. Importantly, overexpression of circ-CAMK2A also enhanced LUAD metastasis in vivo. Mechanistically, miR-615-5p was identified as a direct target of circ-CAMK2A. Circ-CAMK2A up-regulates the expression level of fibronectin 1 by sponging miR-615-5p, thereby increasing MMP2 and MMP9 expression to promote the metastasis of LUAD. Conclusion Circ-CAMK2A plays a crucial role in the metastasis of LUAD, at least partially, by regulating the miR-615-5p/fibronectin 1 axis.

scholarly journals Long non-coding RNA LINC01194 promotes the proliferation, migration and invasion of lung adenocarcinoma cells by targeting miR-641/SETD7 axis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Fanmei Meng ◽  
Yijing Zhou ◽  
Baohua Dong ◽  
Aiqin Dong ◽  
Jingtao Zhang
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Non Coding Rna ◽  
Adenocarcinoma Cells ◽  
Reporter Assays ◽  
Cancer Types ◽  
Long Non Coding Rna

Abstract Background It is increasingly evidenced that long non-coding RNAs (lncRNAs) play an important role in various diseases. LncRNA LINC01194 acts as an oncogene in several cancer types. Nevertheless, the role of LINC01194 in lung adenocarcinoma (LUAD) has not yet been revealed. Methods qRT-PCR was used to detect the expression of LINC01194, miR-641 and SETD7 mRNA, while western blot was exploited to examine SETD7 protein level. Cell proliferation was detected by colony formation and EdU assays. Transwell assays detected cell migration and invasion. TUNEL assay and flow cytometry analysis were used to detect cell apoptosis. RIP, RNA pull down and luciferase reporter assays detected the binding among LINC01194, miR-641 and SETD7. Results LINC01194 was significantly upregulated in LUAD tissues and cell lines. Knockdown of LINC01194 resulted in decreased cell proliferation, migration and invasion, and increased apoptosis. Mechanistic experiments unveiled that LINC01194 augmented SETD7 expression in LUAD cells by competitively interacting with miR-641. Rescue experiments showed that miR-641 inhibition and SETD7 overexpression rescued the repressing impacts on LUAD cell proliferation, migration and invasion caused by LINC01194 knockdown. Conclusion LINC01194 promotes the progression of LUAD by enhancing miR-641-targeted SETD7. The LINC01194/miR-641/SETD7 axis might provide new molecular targets for treating LUAD.

scholarly journals MicroRNA-296-5p inhibits cell metastasis and invasion in nasopharyngeal carcinoma by reversing transforming growth factor-β-induced epithelial–mesenchymal transition

2020 ◽  
Vol 25 (1) ◽  
Author(s):  
Meihui Chen ◽  
Chen Chen ◽  
Haiqing Luo ◽  
Jing Ren ◽  
Qiuqin Dai ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Real Time ◽  
Real Time Pcr ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Cell Metastasis

Abstract Aim To explore the effect of miR-296-5p on the metastasis of nasopharyngeal carcinoma (NPC) cells and investigate the underlying mechanism. Methods The expressions of miR-296-5p in NPC tissues and cells were determined using GSE32920 database analysis and real-time PCR and miRNA microarray assays. An miR-296-5p mimic and inhibitor were transfected into NPC cells. Then, immunofluorescence imaging, scratch wound-healing, transwell migration and invasion assays were used to observe the effects of miR-296-5p on cell metastasis and invasion. Real-time PCR and western blotting were carried out to detect the expressions of genes and proteins related to epithelial–mesenchymal transition (EMT). A dual luciferase reporter assay was used to identify whether TGF-β is the target gene of miR-296-5p. Finally, TGF-β expression plasmids were transfected into NPC cells to verify the role of TGF-β in the miR-296-5p-mediated inhibition of nasopharyngeal carcinoma cell metastasis. Results Our results show that miR-296-5p inhibits the migratory and invasive capacities of NPC cells by targeting TGF-β, which suppresses EMT. Importantly, the miR-296-5p level was significantly lower in human NPC tissues than in adjacent normal tissues. It also negatively correlated with TGF-β and was significantly associated with the lymph node metastasis of patients with NPC. Conclusions Our findings show that miR-296-5p represses the EMT-related metastasis of NPC by targeting TGF-β. This provides new insight into the role of miR-296-5p in regulating NPC metastasis and invasiveness.

scholarly journals CNTN-1 Enhances Chemoresistance in Human Lung Adenocarcinoma Through Induction of Epithelial-Mesenchymal Transition by Targeting the PI3K/Akt Pathway

2017 ◽  
Vol 43 (2) ◽  
pp. 465-480 ◽  
Author(s):  
Ruijie Zhang ◽  
Shenghua Sun ◽  
Fuyun Ji ◽  
Chun Liu ◽  
Hua Lin ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cisplatin Resistance ◽  
Epithelial Mesenchymal Transition ◽  
A549 Cells ◽  
Malignant Progression ◽  
Akt Pathway ◽  
Vimentin Expression ◽  
Mesenchymal Transition

Background/Aims: Chemoresistance has been a major obstacle to the effective treatment of lung cancer. Previously, we found that contactin-1 (CNTN-1) is related to cisplatin resistance in lung adenocarcinoma. Here, we aimed to investigate the underlying mechanism behind the role of CNTN-1 in cisplatin resistance in lung adenocarcinoma. Methods: EMT-associated phenotypes, including alterations in cellular morphology and marker (E-cadherin, N-cadherin and Vimentin) expression, were compared between A549 cells and A549/DDP cells (a cisplatin-resistant cell line of lung adenocarcinoma with abnormal CNTN-1 expression) by using real-time time PCR and Western blotting. Other methods, including CNTN-1 overexpression in A549 cells and CNTN-1 knockdown in A549/DDP cells, were also used to investigate the role of CNTN-1 in mediating the EMT phenotype and thr resulting cisplatin resistance and malignant progression of cancer cells in vitro and in vivo. Results: A549/DDP cells exhibited an EMT phenotype and aggravated malignant behaviors. CNTN-1 knockdown in A549/DDP cells partly reversed the EMT phenotype, increased drug sensitivity, and attenuated the malignant progression whereas CNTN-1 overexpression in A549 cells resulted in the opposite trend. Furthermore, the PI3K/Akt pathway was involved in the effects of CNTN-1 on EMT progression in A549/DDP cells, verified by the xenograft mouse model. Conclusion: CNTN-1 promotes cisplatin resistance in human cisplatin-resistant lung adenocarcinoma through inducing the EMT process by activating the PI3K/Akt signaling pathway. CNTN-1 may be a potential therapeutic target to reverse chemoresistance in cisplatin-resistant lung adenocarcinoma.

scholarly journals miR-1290 contributes to oncogenesis and angiogenesis via targeting of THBS1, DKK3 and, SCAI

Bioimpacts ◽  
2021 ◽  
Author(s):  
Mohammad Hasan Soheilifar ◽  
Majid Pornour ◽  
Massoud Saidijam ◽  
Rezvan Najafi ◽  
Farid Azizi Jalilian ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Umbilical Vein ◽  
Wnt Signaling Pathway ◽  
Tube Formation ◽  
Luciferase Reporter ◽  
Angiogenic Potential ◽  
Umbilical Vein Endothelial Cells ◽  
Critical Process

Introduction: Colorectal cancer (CRC) is the third most common cancer in the world with high mortality, hence, understanding the molecular mechanisms involved in the tumor progression are important for CRC diagnosis and treatment. MicroRNAs (miRNAs) are key gene expression regulators that can function as tumor suppressors or oncogenes in tumor cells, and modulate angiogenesis as a critical process in tumor metastasis. MiR-1290 has been demonstrated as an onco-miRNA in various types of cancer, however, the role of miR-1290 in CRC is not fully understood. This study aimed to investigate the oncogenic and angiogenic potential of miR-1290 in CRC. Methods: Lenti-miR-1290 was transduced into HCT116, SW480, and human umbilical vein endothelial cells (HUVECs). By bioinformatics analysis, we identified thrombospondin 1 (THBS1) as a novel predicted target for miR-1290. Quantitative real-time PCR, western blotting, and luciferase reporter assay were used to demonstrate suppression of miR-1290 target genes including THBS1, Dickkopf Wnt signaling pathway inhibitor 3 (DKK3), and suppressor of cancer cell invasion (SCAI) in HCT116 and HUVECs. Cell cycle analysis, proliferation, migration and, tube formation were determined by flow cytometry, MTT, wound healing, and tube formation assays, respectively. Results: MiR-1290 significantly decreased the expression of THBS1, DKK3, and SCAI. We demonstrated that miR-1290 enhanced proliferation, migration, and angiogenesis partially through suppression of THBS1, DKK3, and SCAI in CRC. Conclusion: These results suggest a novel function of miR-1290 which may contribute to tumorigenesis and angiogenesis in CRC.

scholarly journals Η θεραπευτική σχέση στην ψυχοδυναμική συμβουλευτική και ψυχοθεραπεία: σύγχρονα κλινικά και εμπειρικά δεδομένα

2021 ◽  
Vol 26 (2) ◽  
pp. 32
Author(s):  
Vasiliki Yotsidi ◽  
Kalliopi Kounenou
Keyword(s):  
Therapeutic Relationship ◽  
Therapeutic Process ◽  
Clinical Work ◽  
Real Relationship ◽  
Dynamic Interactions ◽  
Therapeutic Value ◽  
Essential Components ◽  
Key Factor ◽  
Relationship Of

In the psychodynamic approach, the therapeutic relationship stands at the core of the therapeutic process and constitutes a key factor of the effectiveness of treatment. As such, highlighting the psychodynamic components associated with the therapeutic relationship can help reinforce the role of counseling and clinical psychologists, by offering a broader understanding of the various dynamic interactions in clinical work. Specifically, the present paper delineates particular aspects of the therapeutic relationship (e.g. therapeutic alliance, transference, countertransference, real relationship) that should be taken into account in counseling and psychotherapy as essential components of the therapeutic relationship. Current empirical data are presented to demonstrate the importance of these parameters for the therapeutic process and outcome. Emphasis is also placed on the conditions that need to be fulfilled in order to ensure a relationship of therapeutic value, such as the importance of the therapeutic framework and the role of the psychologists / psychotherapists in dealing with enactments. Finally, the benefits of using the potential of the therapeutic relationship in clinical practice are highlighted, for improving both someone’s relationship with oneself and with others.

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