scholarly journals Mettl14 inhibits bladder TIC self-renewal and bladder tumorigenesis through N6-methyladenosine of Notch1

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Chaohui Gu ◽  
Zhiyu Wang ◽  
Naichun Zhou ◽  
Guanru Li ◽  
Yiping Kou ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Rna Stability ◽  
Developed Countries ◽  
Small Population ◽  
Clinical Severity ◽  
Cancer Type ◽  
Tumor Initiating Cells ◽  
Self Renewal ◽  
Common Cancer Type

Abstract Background N6-methyladenosine (m6A) emerges as one of the most important modification of RNA. Bladder cancer is a common cancer type in developed countries, and hundreds of thousands of bladder cancer patients die every year. Materials and methods There are various cells in bladder tumor bulk, and a small population cells defined as tumor initiating cells (TIC) have self-renewal and differentiation capacities. Bladder TICs drive bladder tumorigenesis and metastasis, and their activities are fine regulated. However, the role of N6-methyladenosine in bladder TIC self-renewal is unknown. Results Here, we found a decrease of N6-methyladenosine in bladder tumors and bladder TICs. N6-methyladenosine levels are related to clinical severity and outcome. Mettl14 is lowly expressed in bladder cancer and bladder TICs. Mettl14 knockout promotes the proliferation, self-renewal, metastasis and tumor initiating capacity of bladder TICs, and Mettl14 overexpression exerts an opposite role. Mettl14 and m6A modification participate in the RNA stability of Notch1 mRNA. Notch1 m6A modification inhibits its RNA stability. Notch1 plays an essential role in bladder tumorigenesis and bladder TIC self-renewal. Conclusion This work reveals a novel role of Mettl14 and N6-methyladenosine in bladder tumorigenesis and bladder TICs, adding new layers for bladder TIC regulation and N6-methyladenosine function.

STEM-20. THE ROLE OF HUMAN BETA DEFENSINS IN THE CLONOGENICITY OF GLIOBLASTOMA MULTIFORME

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi25-vi25
Author(s):  
Peggy Harris ◽  
Amber Kerstetter-Fogle ◽  
Anthony Sloan ◽  
Alankrita Raghavan ◽  
Harry Hoffman ◽  
...  
Keyword(s):  
Median Overall Survival ◽  
Poor Response ◽  
Small Population ◽  
Response To Treatment ◽  
Lower Grade ◽  
Cancer Type ◽  
Mrna Levels ◽  
Self Renewal ◽  
Beta Defensins

Abstract INTRODUCTION Glioblastoma (GBM) is the most common primary malignant brain tumor with a median overall survival of 12-15months. GBM aggressiveness and poor response to treatment are often attributed to a small population of stem-like cells referred to as glioma stem cells (GSCs). Human Beta-Defensins (HBDs), a family of small molecules initially thought to function as anti-microbials, have been implicated in various cancers with functions that are cancer type specific, including proinflammatory and immunosuppressive roles. GOAL: This study aimed to elucidate HBDs expression in GSCs and differentiated gioma cells (DGSs). METHODS We identified HBD2 and HBD3 in glioma and GSCs and DGSs by immunofluorescence (IF) and immunohistochemistry (IHC). We also assessed the role HBD2/3 play in GBM oncogenesis by investigating their effects on the self-renewal capacity of GSCs. RESULTS HBD2 and HBD3 are found in both bulk tumor and GSCs by IHC and IF. Expression of HBD2 and HBD3 mRNA levels are elevated in GBM patient tissue in comparison to lower grade gliomas by 16.2 & 1.9 fold (respectively; p < 0.0001). Additionally, transcriptional expression of HBD2 and HBD3 are increased by 0.68 and 1.15 fold respectively in GSCs versus autologous DGCs (p < 0.05; p< 0.005 respectively), suggesting a role for HBD 2/3 in oncogenesis. Interestingly however, HBD2 and HBD3 pretreatment of GSC cell lines showed decreased self-renewal capacity by 34.2 and 66.4% (p < 0.001), determined by the reduced number of large neurospheres ( >250mm). CONCLUSIONS Our results demonstrate the presence of HBD2/3 in GBM samples by IHC and IF with increased HBD2/3 mRNA expression in GBM samples. Interestingly DGCs contain less HBD2/3 than their GCS counterparts, and clonogenicity assays demonstrate a decrease in oncogenesis, suggesting that HBD’s role in proliferation and clonogenicity of DGCs and GSCs may be context dependent, leading to additional questions and future studies.

miR-361-3p Regulates Liver Tumor-initiating Cells Expansion and Chemo-resistance

2020 ◽  
Author(s):  
Shuping Qu ◽  
Xiaobing Zhang ◽  
Hengwei Fan ◽  
Yue Wu ◽  
Jian Zhai ◽  
...  
Keyword(s):  
Liver Tumor ◽  
Cohort Analysis ◽  
The Self ◽  
Tumor Initiating Cells ◽  
Self Renewal ◽  
Sorafenib Treatment ◽  
The Impact

Abstract Background: Increasing evidence shows that liver tumor-initiating cells (T-ICs) closely associated with the progression, metastasis, recurrence and chemo-resistance of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver T-ICs remains unclear. The purpose of our study was to explore the role of miR-361-3p in the expansion of liver T-ICs and the potential molecular mechanism.Results: Flow cytometry analysis was performed to isolate CD24+, CD133+ or EpCAM+ cells from primary HCC cells or HCC cell lines. Real-time PCR was used to detect the expression of miR-361-3p in liver T-ICs. The impact of miR-361-3p on liver T-ICS expansion was investigated both in vivo and in vitro. The correlation between miR-361-3p expression and TACE (transcatheter arterial chemoembolization) or sorafenib benefits in HCC was evaluated in patient cohorts. miR-361-3p expression is upregulated in liver T-ICs. Knockdown of miR-361-3p impairs the self-renewal and tumorigenicity liver T-ICs. Conversely, forced miR-361-3p expression enhances the self-renewal and tumorigenicity liver T-ICs. Mechanistically, miR-361-3p directly targets SOX1 via binding its 3’-UTR in liver T-ICs. Moreover, miR-361-3p knockdown hepatoma cells are more sensitive to cisplatin or sorafenib treatment. Clinical cohort analysis demonstrates that miR-361-3p low HCC patients are benefited from TACE or sorafenib treatment. Conclusions: Our findings revealed the crucial role of the miR-361-3p in liver T-IC expansion and TACE or sorafenib response, rendering miR-361-3p an optimal target for the prevention and intervention in HCC.

scholarly journals Is there an association between prostate cancer and human papillomaviruses?

2017 ◽  
Vol 16 (2) ◽  
pp. 6-12 ◽  
Author(s):  
G. M. Volgareva
Keyword(s):  
Prostate Cancer ◽  
Cervical Cancer Prevention ◽  
Human Papillomaviruses ◽  
Cancer Type ◽  
Incidence And Mortality ◽  
The Russian Federation ◽  
The Given ◽  
Common Cancer Type ◽  
Oncogenic Hpv

Prostate cancer (PC) incidence and mortality are growing steadily the world over including Russia. PC incidence in 2014 made up 14.3 % of all male tumors in the Russian Federation. PC mortality growth rate since 2004 turned out to be topmost among all men’s cancers. PC etiology is poorly understood yet. Thus the role of human papillomaviruses (HPV) belonging to the highly oncogenic types is unclear while in some other human organs they were proven to be powerful carcinogens. Communications keep on emerging from various laboratories by authors who make mutually exclusive conclusions on the role of these viruses in PC genesis. It seems urgent to clarify the given problem from both theoretical and practical viewpoints. Firstly, this is the way to specify the origin of such a common cancer type as PC is. Secondly, if PC association with oncogenic HPV is confirmed the outlook for PC prevention is discovered by means of inoculating of boys with the vaccines designed for cervical cancer prevention. The present review of the literature contains analysis of data on possible HPV involvement in PC genesis.

Role of small nuclear RNAs in eukaryotic gene expression

2013 ◽  
Vol 54 ◽  
pp. 79-90 ◽  
Author(s):  
Saba Valadkhan ◽  
Lalith S. Gunawardane
Keyword(s):  
Gene Expression ◽  
Protein Interactions ◽  
Rna Stability ◽  
Splice Sites ◽  
Branch Site ◽  
Small Nuclear Rnas ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene ◽  
Rna Biogenesis

Eukaryotic cells contain small, highly abundant, nuclear-localized non-coding RNAs [snRNAs (small nuclear RNAs)] which play important roles in splicing of introns from primary genomic transcripts. Through a combination of RNA–RNA and RNA–protein interactions, two of the snRNPs, U1 and U2, recognize the splice sites and the branch site of introns. A complex remodelling of RNA–RNA and protein-based interactions follows, resulting in the assembly of catalytically competent spliceosomes, in which the snRNAs and their bound proteins play central roles. This process involves formation of extensive base-pairing interactions between U2 and U6, U6 and the 5′ splice site, and U5 and the exonic sequences immediately adjacent to the 5′ and 3′ splice sites. Thus RNA–RNA interactions involving U2, U5 and U6 help position the reacting groups of the first and second steps of splicing. In addition, U6 is also thought to participate in formation of the spliceosomal active site. Furthermore, emerging evidence suggests additional roles for snRNAs in regulation of various aspects of RNA biogenesis, from transcription to polyadenylation and RNA stability. These snRNP-mediated regulatory roles probably serve to ensure the co-ordination of the different processes involved in biogenesis of RNAs and point to the central importance of snRNAs in eukaryotic gene expression.

792: Role of Oxidative Stress in Tumorigenic Potential of Bladder Cancer Cells

2005 ◽  
Vol 173 (4S) ◽  
pp. 214-215 ◽  
Author(s):  
Daniel Cho ◽  
Xiao Fang Ha ◽  
J. Andre Melendez ◽  
Louis J. Giorgi ◽  
Badar M. Mian
Keyword(s):  
Oxidative Stress ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Tumorigenic Potential ◽  
Bladder Cancer Cells

How to Assure Stable Development in Unstable Financial Environment?

2007 ◽  
pp. 4-26 ◽  
Author(s):  
M. Ershov
Keyword(s):  
Stock Market ◽  
Developed Countries ◽  
Market Liquidity ◽  
Market Mechanisms ◽  
Russian Economy ◽  
The Developed Countries ◽  
Russian Stock Market ◽  
Stable Development ◽  
Financial Environment

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.

Vitamin A: dietologist’s position

2020 ◽  
pp. 49-57
Author(s):  
S. V. Orlova ◽  
E. A. Nikitina ◽  
L. I. Karushina ◽  
Yu. A. Pigaryova ◽  
O. E. Pronina
Keyword(s):  
Immune Response ◽  
Urinary Tract ◽  
Gastrointestinal Tract ◽  
Vitamin A ◽  
Developed Countries ◽  
Therapeutic Practice ◽  
The Past ◽  
Increased Risk ◽  
Mucous Membranes

Vitamin A (retinol) is one of the key elements for regulating the immune response and controls the division and differentiation of epithelial cells of the mucous membranes of the bronchopulmonary system, gastrointestinal tract, urinary tract, eyes, etc. Its significance in the context of the COVID‑19 pandemic is difficult to overestimate. However, a number of studies conducted in the past have associated the additional intake of vitamin A with an increased risk of developing cancer, as a result of which vitamin A was practically excluded from therapeutic practice in developed countries. Our review highlights the role of vitamin A in maintaining human health and the latest data on its effect on the development mechanisms of somatic pathology.

Physical capital stock, technological upgrading and modernisation in Hungary

2005 ◽  
Vol 55 (2) ◽  
pp. 201-221 ◽  
Author(s):  
Andrea Szalavetz
Keyword(s):  
Capital Accumulation ◽  
Physical Capital ◽  
Developed Countries ◽  
Point Of View ◽  
Technology Generation ◽  
Development Policies ◽  
Specific Factors ◽  
Physical Capital Accumulation

This paper discusses the relation between the quality and quantity indicators of physical capital and modernisation. While international academic literature emphasises the role of intangible factors enabling technology generation and absorption rather than that of physical capital accumulation, this paper argues that the quantity and quality of physical capital are important modernisation factors, particularly in the case of small, undercapitalised countries that recently integrated into the world economy. The paper shows that in Hungary, as opposed to developed countries, the technological upgrading of capital assets was not necessarily accompanied by the upgrading of human capital i.e. the thesis of capital skill complementarity did not apply to the first decade of transformation and capital accumulation in Hungary. Finally, the paper shows that there are large differences between the average technological levels of individual industries. The dualism of the Hungarian economy, which is also manifest in terms of differences in the size of individual industries' technological gaps, is a disadvantage from the point of view of competitiveness. The increasing differences in the size of the technological gaps can be explained not only with industry-specific factors, but also with the weakness of technology and regional development policies, as well as with institutional deficiencies.

Nutrition in inflammatory bowel disease

2009 ◽  
Vol 150 (18) ◽  
pp. 839-845 ◽  
Author(s):  
János Banai
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Fast Food ◽  
Optimal Growth ◽  
Developed Countries ◽  
Aetiological Factor ◽  
Artificial Nutrition ◽  
Food Preservatives ◽  
Inflammatory Bowel

Aetiology of inflammatory bowel disease (IBD) is complex and probably multifactorial. Nutrition has been proposed to be an important aetiological factor for development of IBD. Several components of the diet (such as sugar, fat, fibre, fruit and vegetable, protein, fast food, preservatives etc.) were examined as possible causative agents for IBD. According to some researchers infant feeding (breast feeding) may also contribute to the development of IBD. Though the importance of environmental factors is evidenced by the increasing incidence in developed countries and in migrant population in recent decades, the aetiology of IBD remained unclear. There are many theories, but as yet no dietary approaches have been proved to reduce the risk of developing IBD. The role of nutrition in the management of IBD is better understood. The prevention and correction of malnutrition, the provision of macro- and micronutrients and vitamins and the promotion of optimal growth and development of children are key points of nutritional therapy. In active disease, the effective support of energy and nutrients is a very important part of the therapy. Natural and artificial nutrition or the combination of two can be choosen for supporting therapy of IBD. The author summarises the aetiological and therapeutic role of nutrition in IBD.

Role of The Halal Industry in Recovering the National Economy in Covid-19 Pandemic

2020 ◽  
Vol 8 (2) ◽  
pp. 202-214
Author(s):  
Cucu Susilawati
Keyword(s):  
National Economy ◽  
Banking Sector ◽  
Developed Countries ◽  
Online News ◽  
Financial Industry ◽  
National Economic ◽  
Halal Food ◽  
Vigorous Growth ◽  
Business Sectors

The outbreak of the Covid-19 pandemic in Indonesia is attacking not only public health but also the economy. The presence of Covid-19 has many important impacts on developed countries. There are at least four industries most impacted by this pandemic, including households, MSMEs, companies and the financial industry. However, the halal industry is believed to be more resilient to the Covid-19 pandemic. This durability is because of the principles attributed to the halal sector, namely the importance of fairness, balance and openness. The author’s goal is therefore to carry out more in-depth research on the role of the halal industry in supporting the national economy, which is under pressure because of the COVID-19 pandemic. This type of study is a literature review with a material analysis approach that explores the conditions of the halal industry in Indonesia in depth. The material received is as books, published information, and online news. The findings of this study reveal that there are three halal business sectors that are believed to be more vulnerable to the Covid-19 pandemic in order to facilitate national economic recovery. Halal finance, halal food and halal fashion industries are among them. Halal finance from both the banking sector and the Islamic stock market has proved to be more robust than the mainstream financial sector. Besides guaranteed halal food, its wellbeing is also guaranteed, and halal fashion is now on the rise as Muslim fashion is increasingly innovative and global. We believe the three of them to have experienced vigorous growth, and also to continue to draw customers. And also after the Covid-19 pandemic, these three sectors could survive. Thus the halal industry also contributes to Indonesian economy.

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