scholarly journals MiR-375 attenuates injury of cerebral ischemia/reperfusion via targetting Ctgf

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Jianying Ou ◽  
Li Kou ◽  
Lingyan Liang ◽  
Chaogang Tang
Keyword(s):  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Significant Protection ◽  
Stroke Models ◽  
And Migration ◽  
The Brain ◽  
Insight Into ◽  
Proliferation And Migration

Ischemic stroke is the leading cause of disability and deaths worldwide. MiRNAs have been shown to play an important role in development and pathogenesis of the nervous system. However, the precise function and mechanism of miRNAs are not fully understood in the brain injury induced by ischemia/reperfusion (I/R). Herein, our study showed that miR-375 expression was significantly down-regulated in the rat I/R brain. With the in vivo and in vitro I/R stroke models, we found that miR-375 mimic provides significant protection from injury to cerebral I/R, which is reflected by reduced infarct volumes and cell apoptosis, and increased proliferation and migration of PC12 cells. Mechanistically, our findings showed that miR-375 binds to 3′-UTR region of Ctgf mRNA, subsequently leading to the decreased expression of Ctgf in the I/R brain. Furthermore, we showed that miR-375/Ctgf-mediated protective effects are associated with p21/PI3K/Akt signaling pathways. Our findings thus provide a new insight into the mechanism of cerebral I/R injury and pave a potential new way for the therapy of cerebral I/R injury.

scholarly journals Hypoxic glioma-derived exosomes promote M2-like macrophage polarization by enhancing autophagy induction

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Jianye Xu ◽  
Jian Zhang ◽  
Zongpu Zhang ◽  
Zijie Gao ◽  
Yanhua Qi ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Autophagy Induction ◽  
Antitumor Immunotherapy ◽  
Novel Biomarkers ◽  
And Migration ◽  
Immunosuppressive Microenvironment ◽  
Proliferation And Migration ◽  
Glioma Progression

AbstractExosomes participate in intercellular communication and glioma microenvironment modulation, but the exact mechanisms by which glioma-derived exosomes (GDEs) promote the generation of the immunosuppressive microenvironment are still unclear. Here, we investigated the effects of GDEs on autophagy, the polarization of tumor-associated macrophages (TAMs), and glioma progression. Compared with normoxic glioma-derived exosomes (N-GDEs), hypoxic glioma-derived exosomes (H-GDEs) markedly facilitated autophagy and M2-like macrophage polarization, which subsequently promoted glioma proliferation and migration in vitro and in vivo. Western blot and qRT-PCR analyses indicated that interleukin 6 (IL-6) and miR-155-3p were highly expressed in H-GDEs. Further experiments showed that IL-6 and miR-155-3p induced M2-like macrophage polarization via the IL-6-pSTAT3-miR-155-3p-autophagy-pSTAT3 positive feedback loop, which promotes glioma progression. Our study clarifies a mechanism by which hypoxia and glioma influence autophagy and M2-like macrophage polarization via exosomes, which could advance the formation of the immunosuppressive microenvironment. Our findings suggest that IL-6 and miR-155-3p may be novel biomarkers for diagnosing glioma and that treatments targeting autophagy and the STAT3 pathway may contribute to antitumor immunotherapy.

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.

scholarly journals Circular RNA hsa_circ_0006401 promotes proliferation and metastasis in colorectal carcinoma

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Chenjing Zhang ◽  
Xiaolu Zhou ◽  
Xiaoge Geng ◽  
Yu Zhang ◽  
Jingya Wang ◽  
...  
Keyword(s):  
Splice Junction ◽  
Circular Rna ◽  
Host Gene ◽  
Cell Counting ◽  
Tissue Samples ◽  
Proliferation And Metastasis ◽  
And Migration ◽  
Proliferation And Migration

AbstractDysregulation of circular RNA (circRNA) expression is involved in the progression of cancer. Here, we aimed to study the potential function of hsa_circ_0006401 in colorectal cancer (CRC). CircRNA hsa_circ_0006401 expression levels in CRC and adjacent nontumor tissues were analyzed by real-time quantitative PCR (qRT-PCR) and circRNA in situ hybridization (RNA-ISH). Then, CRC cell proliferation was assessed by cell counting. Wound-healing and transwell assays were utilized to detect the effect of hsa_circ_0006401 on CRC migration. A circRNA-ORF construct was created, and a specific antibody against the splice junction of hsa_circ_0006401 was prepared. Finally, the proteins directly binding to hsa_circ_0006401 peptides were identified by immunoprecipitation combined with mass spectrometry. In our study, we found hsa_circ_0006401 was closely related to CRC metastasis and exhibited upregulated expression in metastatic CRC tissue samples. Proliferation and migration were inhibited in vitro when hsa_circ_0006401 expression was silenced. Downregulation of hsa_circ_0006401 expression decreased CRC proliferation and liver metastasis in vivo. A 198-aa peptide was encoded by sequences of the splice junction absent from col6a3. Hsa_circ_0006401 promoted CRC proliferation and migration by encoding the hsa_circ_0006401 peptide. Hsa_circ_0006401 peptides decreased the mRNA and protein level of the host gene col6a3 by promoting col6a3 mRNA stabilation. In conclusion, our study revealed that circRNAs generated from col6a3 that contain an open-reading frame (ORF) encode a novel 198-aa functional peptide and hsa_circ_0006401 peptides promote stability of the host gene col6a3 mRNA to promote CRC proliferation and metastasis.

scholarly journals Propofol attenuates lung ischemia/reperfusion injury though the involvement of the MALAT1/microRNA-144/GSK3β axis

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Jian-Ping Zhang ◽  
Wei-Jing Zhang ◽  
Miao Yang ◽  
Hua Fang
Keyword(s):  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Loss Of Function

Abstract Background Propofol, an intravenous anesthetic, was proven to protect against lung ischemia/reperfusion (I/R) injury. However, the detailed mechanism of Propofol in lung I/R injury is still elusive. This study was designed to explore the therapeutic effects of Propofol, both in vivo and in vitro, on lung I/R injury and the underlying mechanisms related to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-144 (miR-144)/glycogen synthase kinase-3β (GSK3β). Methods C57BL/6 mice were used to establish a lung I/R injury model while pulmonary microvascular endothelial cells (PMVECs) were constructed as hypoxia/reperfusion (H/R) cellular model, both of which were performed with Propofol treatment. Gain- or loss-of-function approaches were subsequently employed, followed by observation of cell apoptosis in lung tissues and evaluation of proliferative and apoptotic capabilities in H/R cells. Meanwhile, the inflammatory factors, autophagosomes, and autophagy-related proteins were measured. Results Our experimental data revealed that Propofol treatment could decrease the elevated expression of MALAT1 following I/R injury or H/R induction, indicating its protection against lung I/R injury. Additionally, overexpressing MALAT1 or GSK3β promoted the activation of autophagosomes, proinflammatory factor release, and cell apoptosis, suggesting that overexpressing MALAT1 or GSK3β may reverse the protective effects of Propofol against lung I/R injury. MALAT1 was identified to negatively regulate miR-144 to upregulate the GSK3β expression. Conclusion Overall, our study demonstrated that Propofol played a protective role in lung I/R injury by suppressing autophagy and decreasing release of inflammatory factors, with the possible involvement of the MALAT1/miR-144/GSK3β axis.

scholarly journals SMYD3 promotes hepatocellular carcinoma progression by methylating S1PR1 promoters

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Heyun Zhang ◽  
Zhangyu Zheng ◽  
Rongqin Zhang ◽  
Yongcong Yan ◽  
Yaorong Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathways ◽  
Histone Methylation ◽  
Cell Growth And Migration ◽  
Histone 3 ◽  
Sphingosine 1 Phosphate ◽  
And Migration ◽  
Proliferation And Migration

AbstractHepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. SET and MYND domain-containing protein 3 (SMYD3) has been shown to promote the progression of various types of human cancers, including liver cancer; however, the detailed molecular mechanism is still largely unknown. Here, we report that SMYD3 expression in HCC is an independent prognostic factor for survival and promotes the proliferation and migration of HCC cells. We observed that SMYD3 upregulated sphingosine-1-phosphate receptor 1 (S1PR1) promoter activity by methylating histone 3 (H3K4me3). S1PR1 was expressed at high levels in HCC samples, and high S1PR1 expression was associated with shorter survival. S1PR1 expression was also positively correlated with SMYD3 expression in HCC samples. We confirmed that SMYD3 promotes HCC cell growth and migration in vitro and in vivo by upregulating S1PR1 expression. Further investigations revealed that SMYD3 affects critical signaling pathways associated with the progression of HCC through S1PR1. These findings strongly suggest that SMYD3 has a crucial function in HCC progression that is partially mediated by histone methylation at the downstream gene S1PR1, which affects key signaling pathways associated with carcinogenesis and the progression of HCC.

scholarly journals EXTH-64. SMALL GTPASES IN MENINGIOMAS: PROLIFERATION, MIGRATION, SURVIVAL, POTENTIAL TREATMENT AND INTERACTIONS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii101-ii101
Author(s):  
Christoph Kesseler ◽  
Julian Kahr ◽  
Natalie Waldt ◽  
Nele Stroscher ◽  
Josephine Liebig ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Lines ◽  
Small Gtpases ◽  
Potential Treatment ◽  
Rock Inhibitor ◽  
Meningioma Cell ◽  
And Migration ◽  
Proliferation And Migration

Abstract PURPOSE To evaluate the role of the small GTPases RhoA, Rac1 and Cdc42 in meningiomas as therapeutic targets and their interactions in meningiomas. EXPERIMENTAL DESIGN We analyzed expression of GTPases in human meningioma samples and meningioma cell lines of various WHO grades. Malignant IOMM-Lee meningioma cells were used to generate shRNA mediated knockdowns of GTPases RhoA, Rac1 or Cdc42 and to study knockdown effects on proliferation and migration, as well as analysis of cell morphology by confocal microscopy. The same tests were used to investigate effects of the two inhibitors Fasudil and EHT-1864 of malignant IOMM-Lee, KT21 and benign Ben-Men cells and the effects of these drugs on IOMM-Lee knockdown cells. The effects of GTPase knockdowns and Fasudil treatment were studied in terms of overall survival by intracranial xenografts of mice. Potential interactions of GTPases regarding NF2, mTOR and FAK-Paxillin were examined. RESULTS Small GTPases were upregulated in meningiomas of higher tumor grades. Reduced proliferation and migration could be achieved by GTPase knockdown in IOMM-Lee cells. Additionally, the ROCK-inhibitor Fasudil and Rac1-inhibitor EHT-1864 reduced proliferation in different meningioma cell lines and reduced proliferation and migration independent of GTPase knockdowns/status. Moreover, overall survival in vivo could also be increased by knockdowns of RhoA and Rac1 as well as Fasudil treatment. GTPase expression was affected dependent on the NF2 status but effects were not very distinct, indicating that NF2 is not strongly involved in GTPase regulation in meningiomas. In terms of mTOR and FAK-Paxillin signaling, each GTPase changes those pathways in a different manner. CONCLUSION Small GTPases are important effectors in meningioma proliferation and migration in vitro as well as survival in vivo and their inhibition should be considered as potential treatment option.

scholarly journals Inhibitory Effect of a Glutamine Antagonist on Proliferation and Migration of VSMCs via Simultaneous Attenuation of Glycolysis and Oxidative Phosphorylation

2021 ◽  
Vol 22 (11) ◽  
pp. 5602
Author(s):  
Hyeon Young Park ◽  
Mi-Jin Kim ◽  
Seunghyeong Lee ◽  
Jonghwa Jin ◽  
Sungwoo Lee ◽  
...  
Keyword(s):  
Mammalian Target Of Rapamycin ◽  
Inhibitory Effect ◽  
Metabolic Reprogramming ◽  
Neointima Formation ◽  
Artery Ligation ◽  
Carotid Artery Ligation ◽  
And Migration ◽  
Proliferation And Migration

Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to the development of atherosclerosis and restenosis. Glycolysis and glutaminolysis are increased in rapidly proliferating VSMCs to support their increased energy requirements and biomass production. Thus, it is essential to develop new pharmacological tools that regulate metabolic reprogramming in VSMCs for treatment of atherosclerosis. The effects of 6-diazo-5-oxo-L-norleucine (DON), a glutamine antagonist, have been broadly investigated in highly proliferative cells; however, it is unclear whether DON inhibits proliferation of VSMCs and neointima formation. Here, we investigated the effects of DON on neointima formation in vivo as well as proliferation and migration of VSMCs in vitro. DON simultaneously inhibited FBS- or PDGF-stimulated glycolysis and glutaminolysis as well as mammalian target of rapamycin complex I activity in growth factor-stimulated VSMCs, and thereby suppressed their proliferation and migration. Furthermore, a DON-derived prodrug, named JHU-083, significantly attenuated carotid artery ligation-induced neointima formation in mice. Our results suggest that treatment with a glutamine antagonist is a promising approach to prevent progression of atherosclerosis and restenosis.

scholarly journals BSCI-12. Inhibition of melanoma brain metastasis by targeting miR-146a

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii3-iii3
Author(s):  
Jiwei Wang ◽  
Emma Rigg ◽  
Taral R Lunavat ◽  
Wenjing Zhou ◽  
Zichao Feng ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Tumor Cells ◽  
Cell Lines ◽  
Western Blots ◽  
Cell Growth And Migration ◽  
Human Astrocytes ◽  
And Migration ◽  
The Brain

Abstract Background Melanoma has the highest propensity of any cancer to metastasize to the brain, with late-stage patients developing brain metastasis (MBM) in 40% of cases. Survival of patients with MBM is around 8 months with current therapies, illustrating the need for new treatments. MBM development is likely caused by molecular interactions between tumor cells and the brain, constituting the brain metastatic niche. miRNAs delivered by exosomes released by the primary tumor cells may play a role in niche establishment, yet the mechanisms are poorly understood. Here, the aim was to identify miRNAs released by exosomes from melanomas, which may be important in niche establishment and MBM progression. Materials and Methods miRNAs from exosomes collected from human astrocytes, melanocytes, and MBM cell lines were profiled to determine differential expression. Functional in vitro validation was performed by cell growth and migration assays, cytokine arrays, qPCR and Western blots. Functional in vivo studies were performed after miR knockdown in MBM cell lines. An in silico docking study was performed to determine drugs that potentially inhibit transcription of miR-146a to impede MBM development. Results miR-146a was the most upregulated miRNA in exosomes from MBM cells and was highly expressed in human and animal MBM samples. miR-146a mimics activated human astrocytes, shown by increased proliferation and migration, elevated expression of GFAP in vitro and in mouse brain tumor samples, and increased cytokine production. In animal studies, knockdown of miR-146a in MBM cells injected intracardially into mice reduced BM burden and increased animal survival. Based on the docking studies, deserpidine was found to be an effective inhibitor of MBM growth in vitro and in vivo. Conclusions MiR-146a may play an important role in MBM development, and deserpidine is a promising candidate for clinical use.

scholarly journals Knockdown of LncRNA LINC00958 Inhibits the Proliferation and Migration of NSCLC Cells by MiR-204-3p/KIF2A Axis

2021 ◽  
Vol 30 ◽  
pp. 096368972110255
Author(s):  
Qing Wang ◽  
Kai Li ◽  
Xiaoliang Li
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Tumor Model ◽  
Luciferase Reporter ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Increasing evidence suggests that long non-coding RNAs (lncRNAs) function in the tumorigenesis of NSCLC. LINC00958, a newly identified lncRNA, has been reported to be closely linked to tumorigenesis in several cancers. However, its specific role in NSCLC remains unclear. In this study, we determined the expression of LINC00958 in NSCLC by RT-qPCR analysis and evaluated cell proliferation and migration by CCK-8 and transwell assays, respectively. We established a xenograft tumor model to examine the effect of LINC00958 on tumor growth in vivo. Luciferase reporter assays were performed to determine the interaction between LINC00958 and miR-204-3p and the interaction between miR-204-3p and KIF2A. We found that LINC00958 was up-regulated in NSCLC tissues and cell lines. Down-regulation of LINC00958 inhibited cell proliferation and migration in vitro and suppressed tumor growth in vivo. Besides, miR-204-3p was identified as a target of LINC00958 and miR-204-3p inhibitor could reverse the inhibitory effect of LINC00958 knockdown on proliferation and migration of NSCLC cells. We also validated that KIF2A, a direct target of miR-204-3p, was responsible for the biological role of LINC00958. KIF2A antagonized the effect of miR-204-3p on NSCLC cell proliferation and migration and was regulated by LINC00958/miR-204-3p. Taken together, these data indicate that the LINC00958/miR-204-3p/KIF2A axis is critical for NSCLC progression, which might provide a potential therapeutic target of NSCLC.

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