scholarly journals MiR-21-5p inhibition attenuates Warburg effect and stemness maintenance in osteosarcoma cells via inactivation of Wnt/β-catenin signaling

Author(s):  
Yi Yu ◽  
Ziyan Wu ◽  
Zhong Zhou ◽  
Weiguo Zhang

MicroRNA (miR)-21 has been found to be overexpressed in osteosarcoma (OS). The aim of the present study was to investigate the effect of miR-21-5p on the Warburg effect and stemness maintenance in OS cells and its potential molecular mechanism. Herein, miR-21-5p was overexpressed or inhibited in MG-63 cells via transfection with mimics or inhibitors. The effect of miR-21-5p on cell viability, apoptosis, Warburg effect and stemness maintenance were explored in OS cells. The results demonstrated that miR-21-5p inhibition suppressed MG-63 cell viability and enhanced their apoptosis. Additionally, miR-21-5p inhibition attenuated the stemness maintenance of MG-63 cells, as demonstrated by the reduced proportion of CD133-positive MG-63 cells, the decrease in tumorsphere formation capacity, and the downregulation of Sox2, Oct4, and Nanog proteins. Moreover, miR-21-5p inhibition suppressed the Warburg effect in MG-63 cells, as indicated by the decrease in glucose uptake, lactic acid production, and ATP level and the downregulation of proteins involved in the Warburg effect (GLUT1, LDHA, HK2, and PKM2). Furthermore, the results suggested that the effect of miR-21-5p suppression on stemness and the Warburg effect may be associated with the decreased activity of the Wnt/β-catenin pathway in OS cells. Our findings suggest a novel potential biomarker for OS therapy.

1961 ◽  
Vol 22 (4) ◽  
pp. 361-369 ◽  
Author(s):  
RUTH LEVARI ◽  
W. KORNBLUETH ◽  
E. WERTHEIMER

SUMMARY 1. A direct stimulatory effect of insulin, in vitro, on the uptake of galactose, glucosamine and some pentoses by the intact lens, has been established. Stimulation of glucose uptake is perceptible only under certain conditions, and was more pronounced in a medium of bicarbonate buffer than in phosphate. 2. Insulin increased lactic acid production from glucose and from galactose. 3. Chronic diabetes decreased galactose uptake. Insulin, in vitro, restored the uptake to the level of that of normal rat lenses. 4. Phloridzin was found to cancel the effect of insulin. 5. The increase in uptake by insulin was of the same order of magnitude for glucose and galactose, irrespective of the total uptake. The decrease in uptake due to diabetes was quantitatively the same as the increase by insulin in normal rat lenses. The effect of insulin on lactic acid production was identical for both hexoses. 6. The possible existence of two pathways of glucose uptake in the rat lens is discussed.


2015 ◽  
Vol 81 (24) ◽  
pp. 8392-8401 ◽  
Author(s):  
Daehee Kim ◽  
Ji-Yoon Song ◽  
Ji-Sook Hahn

ABSTRACTMetabolic engineering to increase the glucose uptake rate might be beneficial to improve microbial production of various fuels and chemicals. In this study, we enhanced the glucose uptake rate inSaccharomyces cerevisiaeby overexpressing hexose transporters (HXTs). Among the 5 tested HXTs (Hxt1, Hxt2, Hxt3, Hxt4, and Hxt7), overexpression of high-affinity transporter Hxt7 was the most effective in increasing the glucose uptake rate, followed by moderate-affinity transporters Hxt2 and Hxt4. Deletion ofSTD1andMTH1, encoding corepressors ofHXTgenes, exerted differential effects on the glucose uptake rate, depending on the culture conditions. In addition, improved cell growth and glucose uptake rates could be achieved by overexpression ofGCR1, which led to increased transcription levels ofHXT1and ribosomal protein genes. All genetic modifications enhancing the glucose uptake rate also increased the ethanol production rate in wild-typeS. cerevisiae. Furthermore, the growth-promoting effect ofGCR1overexpression was successfully applied to lactic acid production in an engineered lactic acid-producing strain, resulting in a significant improvement of productivity and titers of lactic acid production under acidic fermentation conditions.


1963 ◽  
Vol 205 (2) ◽  
pp. 222-224 ◽  
Author(s):  
Richard O. Moore

The glucose uptake, lactic acid production, and net gas exchange has been measured in adipose tissue from fed, fasted, or fasted and refed rats with and without insulin addition in vitro. Unstimulated adipose tissue from fasted and from fasted and refed rats showed a decreased capacity to take up glucose in vitro and a more negative net gas exchange than similar tissue from fed control animals. Insulin added in vitro increased the glucose uptake and CO2 excess in adipose tissue from fed, fasted, and refed rats, but the response with tissue from refed rats was several times that of the other groups. It is concluded that insulin is required for the marked increase in glucose metabolism associated with the refeeding regimen.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Beatriz Martines de Souza ◽  
Mayara Souza Silva ◽  
Aline Silva Braga ◽  
Patrícia Sanches Kerges Bueno ◽  
Paulo Sergio da Silva Santos ◽  
...  

AbstractThis in vitro study evaluated the protective effect of titanium tetrafluoride (TiF4) varnish and silver diamine fluoride (SDF) solution on the radiation-induced dentin caries. Bovine root dentin samples were irradiated (70 Gy) and treated as follows: (6 h): 4% TiF4 varnish; 5.42% NaF varnish; 30% SDF solution; placebo varnish; or untreated (negative control). Microcosm biofilm was produced from human dental biofilm (from patients with head-neck cancer) mixed with McBain saliva for the first 8 h. After 16 h and from day 2 to day 5, McBain saliva (0.2% sucrose) was replaced daily (37 °C, 5% CO2) (biological triplicate). Demineralization was quantified by transverse microradiography (TMR), while biofilm was analyzed by using viability, colony-forming units (CFU) counting and lactic acid production assays. The data were statistically analyzed by ANOVA (p < 0.05). TiF4 and SDF were able to reduce mineral loss compared to placebo and the negative control. TiF4 and SDF significantly reduced the biofilm viability compared to negative control. TiF4 significantly reduced the CFU count of total microorganism, while only SDF affected total streptococci and mutans streptococci counts. The varnishes induced a reduction in lactic acid production compared to the negative control. TiF4 and SDF may be good alternatives to control the development of radiation-induced dentin caries.


Heliyon ◽  
2021 ◽  
Vol 7 (5) ◽  
pp. e07079
Author(s):  
Joel Romial Ngouénam ◽  
Chancel Hector Momo Kenfack ◽  
Edith Marius Foko Kouam ◽  
Pierre Marie Kaktcham ◽  
Rukesh Maharjan ◽  
...  

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