The emerging role of miR-200 family in metastasis: focus on EMT,CSCs, angiogenesis,and anoikis

Introduction

Cancer is the second major threat to human society and one of the main challenges facing healthcare systems. One of the main problems of cancer care is the metastases of cancer cells that cause 90% of deaths due to cancer. Multiple molecular mechanisms are involved in cancer cell metastasis. Therefore, a better understanding of these molecular mechanisms is necessary for designing restrictive strategies against cancer cell metastasis. Accumulating data suggests that MicroRNAs (miRNAs) are involved in metastasis and invasion of human tumors through regulating multiple genes expression levels that are involved in molecular mechanisms of metastasis. The goal of this review is to present the molecular pathways by which the miR 200 family manifests its effects on EMT, cancer stem cells, angiogenesis, anoikis, and the effects of tumor cell metastases.

Methods

A detailed literature search was conducted to find information about the role of the miR-200 family in the processes involved in metastasis in various databases.

Results

Numerous lines of evidence revealed an association between the mir-200 family and metastasis of human tumors by impressing processes such as cancer stem cells, EMT, angiogenesis, and anoikis.

Conclusions

Understanding the molecular mechanisms associated with metastasis in which the miR-200 family is involved can be effective in treating metastatic cancers.

Graphic abstract

     

Differentials of fertility between polygynous and monogamous marriages in rural Bangladesh

This paper discusses polygynous marriages in rural Bangladesh, using marital status and birth registration data from the Demographic Surveillance System (DSS) of the International Center for Diarrheal Disease Research, for the period 1975-79. Of all the marriages recorded during this period about 5% were polygynous. To identify the women polygynously married, 1974 census data of the DSS area were used. The difference in age at marriage between the polygynous groom and his subsequent wife was 15 years on average. The socioeconomic indicators studied were education, occupation and area of dwelling space. In general, these indicators between women in monogamous marriages were significantly higher than between the women in polygynous unions. During the period 1976-79, 863 polygynous marriages were recorded (4.9% of all marriages in the study area). Polygynous marriages were found to be less frequent among men with 2ndary and higher levels of education. The highest proportion of polygynous marriages occurred among husbands with no schooling or Koranic education. The general fertility rate of women in monogamous marriages was significantly higher than for women in polygynous marriages, overall and in all age groups except 20-24. During the period 1975-79, the mean number of liveborn children for monogamous women was higher than that of polygynous women.     

Ecology of deepwater rice-fields in Bangladesh 3. Associated algae and macrophytes

1. Aquatic macrophytes formed dense beds in fallow areas during the four and a half months of the flood season in all but one deepwater rice-growing location in Bangladesh; these included several types of life-form, but the fine-leaved species, Myriophyllum sp., Najas indica, Utricularia stellaris were often especially abundant. The same species grew inside deepwater rice fields, but at much lower densities. A similar contrast occurred for the algae, although deepwater rice often developed dense masses of epiphytes on aquatic roots, stems and leaf sheaths, when plants were growing in isolated, well-illuminated situations.
2. Two widespread algae, Aulosira fertilissima and Scytonema mirabile, were equally successful on soil in the period prior to the arrival of floodwaters and floating on the surface of the water during the flood season. Other species common during the flood season differed from those common on soil.
3. Most blue-green algae inside deepwater rice fields were heterocystous; the only species not so, but forming distinct colonies, was Aphanothece stagnina. However only non-heterocystous forms were found at one location in south Bangladesh (Phaltita) and a change from heterocystous to non-heterocystous forms was noted at the main research site (near Sonargaon) during late September in at least one year. The water column at the former was almost entirely anoxic, while the change at the latter occurred at a time when the water sometimes became anoxic during the night. It is suggested that differences in ability to tolerate anoxic periods may be a key factor in determining the success of the algal and vascular plant species in the different micro-habitats within these DWR-growing areas.
4. Although diatoms were quantitatively only a minor component of the algal biomass, they became more frequent later in the season when the water became microaerobic or anoxic for part of the day. Navicula confervacea was overall the most abundant species at the two main research locations.

     

Ecology of deepwater rice-fields in Bangladesh 4. Nitrogen fixation by blue-green algal communities

1. Aquatic macrophytes formed dense beds in fallow areas during the four and a half months of the flood season in all but one deepwater rice-growing location in Bangladesh; these included several types of life-form, but the fine-leaved species, Myriophyllum sp., Najas indica, Utricularia stellaris were often especially abundant. The same species grew inside deepwater rice fields, but at much lower densities. A similar contrast occurred for the algae, although deepwater rice often developed dense masses of epiphytes on aquatic roots, stems and leaf sheaths, when plants were growing in isolated, well-illuminated situations.
2. Two widespread algae, Aulosira fertilissima and Scytonema mirabile, were equally successful on soil in the period prior to the arrival of floodwaters and floating on the surface of the water during the flood season. Other species common during the flood season differed from those common on soil.
3. Most blue-green algae inside deepwater rice fields were heterocystous; the only species not so, but forming distinct colonies, was Aphanothece stagnina. However only non-heterocystous forms were found at one location in south Bangladesh (Phaltita) and a change from heterocystous to non-heterocystous forms was noted at the main research site (near Sonargaon) during late September in at least one year. The water column at the former was almost entirely anoxic, while the change at the latter occurred at a time when the water sometimes became anoxic during the night. It is suggested that differences in ability to tolerate anoxic periods may be a key factor in determining the success of the algal and vascular plant species in the different micro-habitats within these DWR-growing areas.
4. Although diatoms were quantitatively only a minor component of the algal biomass, they became more frequent later in the season when the water became microaerobic or anoxic for part of the day. Navicula confervacea was overall the most abundant species at the two main research locations.

     

Response of Sesbania grandiflora to Inoculation of Soil with Vesicular-Arbuscular Mycorrhizal Fungi

A greenhouse experiment was conducted to determine the influence of two tropical isolates of Glomus fasciculatum and Glomus mosseae on the nutrient uptake and growth of Sesbania grandiflora. Inoculation of sterile soil with the fungi significantly improved growth and nutrient uptake by S. grandiflora, but the response of the legume was markedly better when the soil was inoculated with G. fasciculatum than when it was inoculated with G. mosseae. Nutrient uptake and growth of S. grandiflora in nonsterile soil was also significantly stimulated by inoculation, but the legume did not respond differently to the two endophytes under this condition.     

The effects of chlorhexidine on the maximum specific growth rate, biomass and hydrolytic enzyme production of Bacteroides gingivalis grown in continuous culture

Bacteroides gingivalis was grown in continuous culture in the presence of chlorhexidine. Maximum specific growth rates and biomass levels initially increased but then decreased as the chlorhexidine level increased from 0 to 30 μg/ml. Total inhibition of growth occurred when the chlorhexidine concentration reached 60 μg/ml. The steady-state levels of cell-bound, extracellular vesicle and extracellular soluble enzymes, trypsin-like protease, alkaline phosphatase and N -acetyl-β-glucosaminidase were measured. With increasing sub-lethal concentrations of chlorhexidine, levels of alkaline phosphatase increased noticeably in all three fractions of culture, whilst cell-bound and extracellular vesicle levels of N -acetyl-β-glucosaminidase remained approximately constant. Extracellular soluble levels of alkaline phosphatase and N -acetyl-β-glucosaminidase increased with increasing levels of chlorhexidine. The levels of trypsin-like protease decreased significantly in all fractions of the culture when cells were grown in the presence of chlorhexidine. Thus, chlorhexidine has a differential effect on the production of B. gingivalis hydrolytic enzymes.     

Effect of density on age-specific mortality in Drosophila: a density supplementation experiment

Age-specific mortality rates were studied at two adult density levels in four inbred lines of Drosophila melanogaster. In experimental populations, adult densities were maintained at constant levels throughout the experiment by replacing dead flies with live, marked mutants. In control populations, densities declined naturally as the cohorts aged. For all experimental populations the best mortality model is the two-stage Gompertz model, with slower mortality acceleration at older ages. Flies in the experimental populations generally lived longer than flies in control populations, regardless of sex, genotype, or initial density level. The data demonstrate that deceleration of age-specific mortality rates at older ages is not caused by declining cohort densities. Mortality deceleration is a real phenomenon that raises serious questions about the evolution of senescence.     

Reduced glutathione esters—antidotes to toxicity. Cytotoxicity induced by hydrogen peroxide, 1-chloro-2,4-dinitrobenzene,and menadione in murine P388D1 macrophages in vitro

Repletion of depleted cellular reduced glutathione (GSH) levels in oxidative stress and exposure to arylating agents is a strategy for the development of antidotes to chemical toxicity. The effect of GSH, reduced glutathione ethyl monoester (GSHEt), and reduced glutathione ethyl diester (GSHEt₂) on the cytotoxicity of hydrogen peroxide, 1-chloro-2,4-dinitrobenzene (CDNB), and menadione to P388D₁ macrophages in vitro was investigated. The median toxic concentration TC₅₀ values of the toxicants were hydrogen peroxide 24 ± 2 mM (N = 19), CDNB 63 ± 6 μM (N = 18), and menadione 30 ± 4 μM (N = 22). Reduced glutathione, GSHEt, and GSHEt₂ were poor antidotes to hydrogen peroxide toxicity. Indeed, the observed antidote effects were attributed to the nonenzymatic reaction of the GSH derivatives with hydrogen peroxide in the extracellular medium. Reduced glutathione ethyl diester was a more potent antidote of CDNB- and menadione-mediated toxicity than GSHEt and GSH. For cell incubations with the approximate median toxic concentration TC₅₀ values of hydrogen peroxide, CDNB, and menadione, the respective median effective antidote concentration EC₅₀ values were GSHEt 23.8 ± 4.1 mM (N = 9), 3.6 ± 0.6 mM (N = 11), and 226 ± 93 μM (N = 12); and GSHEt₂ 20.4 ± 1.9 mM (N = 6), 603 ± 2 μM (N = 9), and 7.6 ± 2.3 μM (N = 12). Reduced glutathione ethyl diester was a potent antidote to CDNB- and menadione-induced toxicities but not to hydrogen peroxide-induced toxicity under acute intoxication conditions. © 1996 John Wiley & Sons, Inc.