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

     

Epithelium Expressing the E7 Oncoprotein of HPV16 Attracts Immune-Modulatory Dendritic Cells to the Skin and Suppresses Their Antigen-Processing Capacity

Antigen presenting cells (APCs) in skin can promote either antigen-specific effector functions or antigen tolerance, and thus determine clearance or persistence of cutaneous viral infections. Human papillomavirus (HPV) infections can persist in squamous epithelium in immunocompetent individuals, and some persisting HPV infections, particularly with HPV16, promote malignant epithelial transformation. Here, we investigate whether local expression of the HPV16 protein most associated with malignant transformation, HPV16-E7, affects the phenotype and function of APC subsets in the skin. We demonstrate an expanded population of Langerhans cells in HPV16-E7 transgenic skin with distinct cell surface markers which express immune-modulatory enzymes and cytokines not expressed by cells from non transgenic skin. Furthermore, HPV16-E7 transgene expression in keratinocytes attracts new APC subsets to the epidermis. In vivo migration and transport of antigen to the draining lymph node by these APCs is markedly enhanced in HPV16-E7 expressing skin, whereas antigen-processing, as measured by proteolytic cleavage of DQ-OVA and activation of T cells in vivo by APCs, is significantly impaired. These data suggest that local expression of HPV16-E7 in keratinocytes can contribute to persisting infection with this oncogenic virus, by altering the phenotype and function of local APCs.     

M89V Sialic Acid Acetyl Esterase (SIAE) and All Other Non-Synonymous Common Variants of This Gene Are Catalytically Normal

Catalytically defective rare variants of Sialic acid Acetyl Esterase (SIAE) have previously been linked to autoimmunity. Studies presented here confirm that the M89V SIAE protein and all other products of common variant alleles of SIAE are catalytically normal. Although overexpressing transfected non-lymphoid cells secrete small amounts of SIAE that can associate with the cell surface, normal human lymphocytes do not exhibit cell surface SIAE, supporting genetic evidence in mice that indicates that this protein functions in a lymphocyte intrinsic manner. Analyses of the plasma proteome also indicate that SIAE is not secreted in vivo. A re-analysis exclusively of catalytically defective rare variant alleles of SIAE in subjects in which this gene was completely sequenced confirmed an association of SIAE with autoimmunity. A subset of catalytically defective rare variant SIAE alleles has previously been typed in a large genotyping study comparing a diverse group of disease subjects and controls; our re-analysis of this data shows that catalytically defective alleles are enriched in disease subjects. These data suggest that SIAE may be associated with autoimmunity and that further study of catalytically defective rare variant SIAE alleles in terms of autoimmune disease susceptibility is strongly warranted.     

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.     

Actual vs perceived profitability: A study of floral choice of honey bees

The relationship between actual and perceived profitability was investigated by quantifying choice behavior of foraging honey bees (Apis mellifera).Rate of net energy gain was used as a measure of profitability. Individual bees repeatedly chose between a yellow and a blue tubular artificial flower which had different associated profitabilities. Handling costs were manipulated by using flowers of different depth;energy gains were manipulated by using different volumes of a 20% (w/w) sucrose solution. Bees' discrimination between the two flowers increased as the absolute difference in profitabilities increased and discrimination decreased as profitabilities of both flowers increased. Therefore, discrimination depended on the relative difference in profitability between flowers, and therefore, perception was a nonlinear function of actual rates of net energy gain. The results also suggested that motivation to choose between flowers depended on the level of profitability. We suggest that nonlinear perceptual scales and motivation should be incorporated into models of food choice as constraints and should be considered in the design of experiments used to test predictions of models and in the interpretation of experimental results.     

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.