scholarly journals MiRNA-144-3p inhibits high glucose induced cell proliferation through suppressing FGF16

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Cuimin Chen ◽  
Chunyan Zhao ◽  
Cao Gu ◽  
Xiao Cui ◽  
Jinhui Wu

Abstract As a major cause of blindness, diabetic retinopathy (DR) is often found in the developed countries. Our previous study identified a down-regulated miRNA: miR-144-3p in response to hyperglycemia. The present study aims to investigate the role of miR-144-3p in proliferation of microvascular epithelial cells. Endothelial cells were treated with different concentrations of glucose, after which miR-144-3p were detected with real-time PCR assay. MiR-144-3p mimics or inhibitors were used to increase or knockdown the level of this miRNA. Western blotting assay and ELISA assay were used to measure the expression and concentration of VEGF protein. 5-Bromo-2-deoxyUridine (BrdU) labeled cell cycle assay was used to detect cells in S phase. MiRNA targets were predicted by using a TargetScan tool, and were further verified by luciferase reporter assay. In the present study, we focussed on a significantly down-regulated miRNA, miR-144-3p, and investigated its role in high glucose (HG) induced cell proliferation. Our data showed that miR-144-3p mimics significantly inhibited HG induced cell proliferation and reduced the percentage of cells in S phase. HG induced up-regulation of VEGF was also prohibited by miR-144-3p mimics. Through wound-healing assay, we found that miR-144-3p suppressed cell migration after HG treatments. Moreover, we predicted and proved that fibroblast growth factor (FGF)16 is a direct target of miR-144-3p. Finally, miR-144-3p attenuated HG induced MAPK activation. In conclusion, we demonstrated that miR-144-3p inhibited high glucose-induced cell proliferation through suppressing FGF16 and MAPK signaling pathway, suggesting a possible role of miR-144-FGF16 in the development of DR.

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Gang Wu ◽  
Zhixi Li ◽  
Youyu Wang ◽  
Xueming Ju ◽  
Rui Huang

Hepatocellular carcinoma (HCC) is the most common type of malignancy of the liver and has been reported as the third most frequent cause of cancer associated death worldwide. Accumulating evidence showed that the expression of miR-34a was abnormal in HCC patients; however, the role of miR-34a in HCC is not clear. In this study, we have observed low expression of the miR-34a in both HCC tissues and hepatoma cell line as compared to normal control. Further to investigate the role of miR-34a in HCC development, HepG2 cells were transfected with miR-34a mimic. Following transfection, miR-34a expression was significantly increased, which further repressed proliferation of HepG2 cells. Bioinformatics, Luciferase Reporter, RT-qPCR, and western blotting assays indicated that special AT-rich sequence-binding protein-2 (SATB2) is a direct target of miR-34a in HCC cells. There was a negative correlation between the expression levels of SATB2 and miR-34a. Investigation into the molecular mechanism indicated that miR-34a regulated cell proliferation through inhibiting SATB2. Therefore, the results of the present study may improve understanding regarding the role of miR-34a in regulating cell proliferation and contribute to the development of novel therapy of HCC.


2007 ◽  
pp. 4-26 ◽  
Author(s):  
M. Ershov

Growing involvement of Russian economy in international economic sphere increases the role of external risks. Financial problems which the developed countries are encountered with today result in volatility of Russian stock market, liquidity problems for banks, unstable prices. These factors in total may put longer-term prospects of economic growth in jeopardy. Monetary, foreign exchange and stock market mechanisms become the centerpiece of economic policy approaches which should provide for stable development in the shaky environment.


Author(s):  
Tikhon Sergeyevich Yarovoy

The article is devoted to the research of goals and functions of lobbying activity. The author has processed the ideas of domestic and foreign scientists, proposed his own approaches to the definition of goals and functions of lobbying activities through the prism of public administration. As a result, a generalized vision of the goals and functions of lobbying activities as interrelated elements of the lobbying system was proposed, and a forecast for further evolution of the goals and functions of domestic lobbying was provided. The analysis of lobbying functions allowed us to notice the tendencies in shifting the goals of this activity. If the objectives were fully covered by functions such as mediation between citizens and the state, the information function and the function of organizing plurality of public interests, then the role of strengthening the self-organization of civil society and the function of compromise become increasingly important in the process of formation in the developed countries of civil society and the development of telecommunication technologies. Ukrainian lobbyism will not be left to the side of this process. Already, politicians of the highest level, leaders of financial and industrial groups have to act, adjust their goals (even if they are — declared), taking into account the reaction of the public. In the future, this trend will only increase. The analysis of current research and political events provides all grounds for believing that, while proper regulatory legislation is being formed in Ukraine, the goals and functions of domestic lobbying will essentially shift towards a compromise with the public. It is noted that in spite of the existence of a basic direction of action, lobbying may have several ramified goals. Guided by the goals set, lobbyism can manifest itself in various spheres of the political system of society, combining the closely intertwined interests of various actors in the lobbying process, or even — contrasting them.


2019 ◽  
Vol 18 (1) ◽  
pp. 78-87 ◽  
Author(s):  
Jian-kai Yang ◽  
Hong-jiang Liu ◽  
Yuanyu Wang ◽  
Chen Li ◽  
Ji-peng Yang ◽  
...  

Background and Objective: Exosomes communicate inter-cellularly and miRNAs play critical roles in this scenario. MiR-214-5p was implicated in multiple tumors with diverse functions uncovered. However, whether miR-214-5p is mechanistically involved in glioblastoma, especially via exosomal pathway, is still elusive. Here we sought to comprehensively address the critical role of exosomal miR-214-5p in glioblastoma (GBM) microenvironment.Methods:The relative expression of miR-214-5p was determined by real-time PCR. Cell viability and migration were measured by MTT and transwell chamber assays, respectively. The secretory cytokines were measured with ELISA kits. The regulatory effect of miR-214-5p on CXCR5 expression was interrogated by luciferase reporter assay. Protein level was analyzed by Western blot.Results:We demonstrated that miR-214-5p was aberrantly overexpressed in GBM and associated with poorer clinical prognosis. High level of miR-214-5p significantly contributed to cell proliferation and migration. GBM-derived exosomal miR-214-5p promoted inflammatory response in primary microglia upon lipopolysaccharide challenge. We further identified CXCR5 as the direct target of miR-214- 5p in this setting.Conclusion:Overexpression of miR-214-5p in GBM modulated the inflammatory response in microglia via exosomal transfer.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yarong Guo ◽  
Bao Chai ◽  
Junmei Jia ◽  
Mudan Yang ◽  
Yanjun Li ◽  
...  

Abstract Objective Dysregulation of KLF7 participates in the development of various cancers, but it is unclear whether there is a link between HCC and aberrant expression of KLF7. The aim of this study was to investigate the role of KLF7 in proliferation and migration of hepatocellular carcinoma (HCC) cells. Methods CCK8, colony growth, transwell, cell cycle analysis and apoptosis detection were performed to explore the effect of KLF7, VPS35 and Ccdc85c on cell function in vitro. Xenografted tumor growth was used to assess in vivo role of KLF7. Chip-qPCR and luciferase reporter assays were applied to check whether KLF7 regulated VPS35 at transcriptional manner. Co-IP assay was performed to detect the interaction between VPS35 and Ccdc85c. Immunohistochemical staining and qRT-PCR analysis were performed in human HCC sampels to study the clinical significance of KLF7, VPS35 and β-catenin. Results Firstly, KLF7 was highly expressed in human HCC samples and correlated with patients’ differentiation and metastasis status. KLF7 overexpression contributed to cell proliferation and invasion of HCC cells in vitro and in vivo. KLF7 transcriptional activation of VPS35 was necessary for HCC tumor growth and metastasis. Further, co-IP studies revealed that VPS35 could interact with Ccdc85c in HCC cells. Rescue assay confirmed that overexpression of VPS35 and knockdown of Ccdc85c abolished the VPS35-medicated promotion effect on cell proliferation and invasion. Finally, KLF7/VPS35 axis regulated Ccdc85c, which involved in activation of β-catenin signaling pathway, confirmed using β-catenin inhibitor, GK974. Functional studies suggested that downregulation of Ccdc85c partly reversed the capacity of cell proliferation and invasion in HCC cells, which was regulated by VPS35 upregulation. Lastly, there was a positive correlation among KLF7, VPS35 and active-β-catenin in human HCC patients. Conclusion We demonstrated that KLF7/VPS35 axis promoted HCC cell progression by activating Ccdc85c-medicated β-catenin pathway. Targeting this signal axis might be a potential treatment strategy for HCC.


2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Xiaoguang Gu ◽  
Jianan Zhang ◽  
Yajuan Ran ◽  
Hena Pan ◽  
JinHong Jia ◽  
...  

AbstractCircular RNAs have been reported to play significant roles in regulating pathophysiological processes while also guiding clinical diagnosis and treatment of hepatocellular carcinoma (HCC). However, only a few circRNAs have been identified thus far. Herein, we investigated the role of a specific closed-loop structure of hsa_circ_101555 that was generated by back-splicing of the host gene casein kinase 1 gamma 1 (CSNK1G1) in the development and proliferation of HCC. We investigated the expression of Hsa_circ_101555 in HCC and normal tissues using bioinformatics. The expression level of hsa_circ_101555 was further detected by fluorescence in situ hybridization and qRT-PCR in ten HCC patients. Transwell, migration, WST-1 assays, and colony formation assays were used to evaluate the role of hsa_circ_101555 in HCC development and proliferation. The regulatory mechanisms of hsa_circ_101555 in miR-145-5p and CDCA3 were determined by dual luciferase reporter assay. A mouse xenograft model was also used to determine the effect of hsa_circ_101555 on HCC growth in vivo. hsa_circ_101555 showed greater stability than the linear RNA; while in vitro and in vivo results demonstrated that hsa_circ_101555 silencing significantly suppressed cell proliferation, migration, and invasion of HCC cells. Rescue experiments further demonstrated that suppression of miR-145-5p significantly attenuated the biological effects of hsa_circ_101555 knockdown in HCC cells. We also identified a putative oncogene CDCA3 as a potential miR-145-5p target. Thus, our results demonstrated that hsa_circ_101555 might function as a competing endogenous RNA of miR-145-5p to upregulate CDCA3 expression in HCC. These findings suggest that hsa_circ_101555 may be a potential therapeutic target for patients with HCC.


2021 ◽  
Vol 22 (11) ◽  
pp. 5590
Author(s):  
Clément Veys ◽  
Abderrahim Benmoussa ◽  
Romain Contentin ◽  
Amandine Duchemin ◽  
Emilie Brotin ◽  
...  

Chondrosarcomas are malignant bone tumors. Their abundant cartilage-like extracellular matrix and their hypoxic microenvironment contribute to their resistance to chemotherapy and radiotherapy, and no effective therapy is currently available. MicroRNAs (miRNAs) may be an interesting alternative in the development of therapeutic options. Here, for the first time in chondrosarcoma cells, we carried out high-throughput functional screening using impedancemetry, and identified five miRNAs with potential antiproliferative or chemosensitive effects on SW1353 chondrosarcoma cells. The cytotoxic effects of miR-342-5p and miR-491-5p were confirmed on three chondrosarcoma cell lines, using functional validation under normoxia and hypoxia. Both miRNAs induced apoptosis and miR-342-5p also induced autophagy. Western blots and luciferase reporter assays identified for the first time Bcl-2 as a direct target of miR-342-5p, and also Bcl-xL as a direct target of both miR-342-5p and miR-491-5p in chondrosarcoma cells. MiR-491-5p also inhibited EGFR expression. Finally, only miR-342-5p induced cell death on a relevant 3D chondrosarcoma organoid model under hypoxia that mimics the in vivo microenvironment. Altogether, our results revealed the tumor suppressive activity of miR-342-5p, and to a lesser extent of miR-491-5p, on chondrosarcoma lines. Through this study, we also confirmed the potential of Bcl-2 family members as therapeutic targets in chondrosarcomas.


1969 ◽  
Vol 8 (I1) ◽  
pp. xi-xii

The contents of ILM for the period from 1962 to 1969 reflect several significant developments: (1) the entry on the international scene of many new countries and their establishment of relations with the developed countries, particularly in the fields of commerce and trade and of investment; (2) the prevalence of armed conflict and the use of military force in the unsettled conditions resulting from the decolonization process and from continued antagonisms between the superpowers; (3) the pervasive role of international organizations, both global and regional, general and specialized; and (4) the continued predominance of national courts in the judicial consideration of questions of international law and the shift from general to specialized tribunals in the resolution of disputes by international arbitration and adjudication.


Author(s):  
Jane M. Hoey

The newly developing countries desire not only political independence but also economic progress for their people—a progress which they can see, and are now aware of, in the rest of the world. The role of the developed countries is to extend aid to the needy. Moral foundations underlie the donor's contributions, but they are more than that, they are the means for acquiring support for international aid in the donor's country. The United States must assume the leader ship among' the free nations in granting aid; she must accept this role because of her economic achievements and technologi cal advantages. Donators of such aid should take cognizance of the complementary character and interrelatedness of economic and social development. For economic development, however much it is sought, is not an end in itself, rather the aim is the well-being and happiness of the individual. Such a goal neces sitates economic aid accompanied by social aid. Social welfare can also be a vehicle to achieve peace, inasmuch as people-to- people relationships generate brotherly love—the only lasting foundation for peace.—Ed.


2019 ◽  
Vol 9 (4) ◽  
pp. 249-252
Author(s):  
ARUNKUMAR B ◽  
GURUNATHAN A

Start-up is a basic thing that a person trying to do something real and new, it has high rates of failure, but the minority of successes includes companies that have evolved as giant and market setters. People who use technology for being entrepreneurs are called as technopreneurs, being born the risk in business in addition to being accomplished the achievement level in innovative and initiative a new kind of product and service to the community. India is enjoying with the fruitful result on the progress of start-up environment which it has been focusing for a long time, the best time for promoting the techno start-up to be apillar of strength in the forthcoming trends. The boom of technopreneurs of our nation had been targeted by the developed countries since 2010. A new benchmark may be set in heavily offering number of opportunities to extent the business, which is also a next level of the start-up environmentin the current scenario and the efforts are taken by the Indian Government. The Technopreneurship's growth and contribution to the start-up technopreneurs in Indian context are catered in this paper and in addition new schemes and well equipped technology parks will be effectuated for the goodness of the new start-up.


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