Regulatory Roles of Six-Transmembrane Epithelial Antigen of the Prostate Family Members in the Occurrence and Development of Malignant Tumors

The human six-transmembrane epithelial antigen of the prostate (STEAP) proteins, which include STEAP1–4 and atypical STEAP1B, contain six transmembrane domains and are located in the cell membrane. STEAPs are considered archaeal metal oxidoreductases, based on their heme groups and F420H2:NADP+ oxidoreductase (FNO)-like structures, and play an important role in cell metal metabolism. Interestingly, STEAPs not only participate in biological processes, such as molecular transport, cell cycling, immune response, and intracellular and extracellular activities, but also are closely related to the occurrence and development of several diseases, especially malignant tumors. Up to now, the expression patterns of STEAPs have been found to be diverse in different types of tumors, with controversial participation in different aspects of malignancy, such as cell proliferation, migration, invasion, apoptosis, and therapeutic resistance. It is clinically important to explore the potential roles of STEAPs as new immunotherapeutic targets for the treatment of different malignant tumors. Therefore, this review focuses on the molecular mechanism and function of STEAPs in the occurrence and development of different cancers in order to understand the role of STEAPs in cancer and provide a new theoretical basis for the treatment of diverse cancers.

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Targeting MUC15 Protein in Cancer: Molecular Mechanisms and Therapeutic Perspectives

Current Cancer Drug Targets ◽

10.2174/1568009620666200601140639 ◽

2020 ◽

Vol 20 (9) ◽

pp. 647-653

Author(s):

Simei Zhang ◽

Wunai Zhang ◽

Ying Xiao ◽

Tao Qin ◽

Yangyang Yue ◽

...

Keyword(s):

Molecular Mechanisms ◽

Malignant Tumors ◽

Transmembrane Protein ◽

Cellular Growth ◽

Current Evidence ◽

Aberrant Expression ◽

Different Types ◽

And Function ◽

Precise Role

MUC15, a member of the mucin family, is a heavily glycosylated transmembrane protein with the primary functions of lubricating surfaces, establishing a selective molecular barrier at the epithelium and mediating signal transduction. Aberrant expression of MUC15 plays a crucial role in the progression of multiple diseases, including malignant tumors. MUC15 has been identified as a tumor suppressor, but current evidence indicate its function as an oncogene in different types of cancers. MUC15 has been shown to be involved in the development of cancer and influence cellular growth, adhesion, invasion, metastasis and immune immunomodulation. However, the precise role of MUC15 in tumour development has not been thoroughly clarified. Here, we systematically summarize the structure and function of MUC15 in cancer, and discuss its potential role in cancer treatment.

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MiRNA Expression in Neuroendocrine Neoplasms of Frequent Localizations

Non-Coding RNA ◽

10.3390/ncrna7030038 ◽

2021 ◽

Vol 7 (3) ◽

pp. 38

Author(s):

Alexandra Korotaeva ◽

Danzan Mansorunov ◽

Natalya Apanovich ◽

Anna Kuzevanova ◽

Alexander Karpukhin

Keyword(s):

Mirna Expression ◽

Malignant Tumors ◽

Neuroendocrine Neoplasms ◽

Specific Expression ◽

Clinical Biomarkers ◽

Different Types ◽

Functional Features ◽

First Time ◽

Potential Biomarkers

Neuroendocrine neoplasms (NEN) are infrequent malignant tumors of a neuroendocrine nature that arise in various organs. They occur most frequently in the lungs, intestines, stomach and pancreas. Molecular diagnostics and prognosis of NEN development are highly relevant. The role of clinical biomarkers can be played by microRNAs (miRNAs). This work is devoted to the analysis of data on miRNA expression in NENs. For the first time, a search for specificity or a community of their functional characteristics in different types of NEN was carried out. Their properties as biomarkers were also analyzed. To date, more than 100 miRNAs have been characterized as differentially expressed and significant for the development of NEN tumors. Only about 10% of the studied miRNAs are expressed in several types of NEN; differential expression of the remaining 90% was found only in tumors of specific localizations. A significant number of miRNAs have been identified as potential biomarkers. However, only a few miRNAs have values that characterized their quality as markers. The analysis demonstrates the predominant specific expression of miRNA in each studied type of NEN. This indicates that miRNA’s functional features are predominantly influenced by the tissue in which they are formed.

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MicroRNAs: Biological Regulators in Pathogen–Host Interactions

Cells ◽

10.3390/cells9010113 ◽

2020 ◽

Vol 9 (1) ◽

pp. 113 ◽

Cited By ~ 3

Author(s):

Stephanie Maia Acuña ◽

Lucile Maria Floeter-Winter ◽

Sandra Marcia Muxel

Keyword(s):

Immune Response ◽

Infectious Diseases ◽

Small Rnas ◽

Immune Cell ◽

Fine Tuning ◽

Biological Processes ◽

Host Interactions ◽

The Past ◽

Biological Aspects

An inflammatory response is essential for combating invading pathogens. Several effector components, as well as immune cell populations, are involved in mounting an immune response, thereby destroying pathogenic organisms such as bacteria, fungi, viruses, and parasites. In the past decade, microRNAs (miRNAs), a group of noncoding small RNAs, have emerged as functionally significant regulatory molecules with the significant capability of fine-tuning biological processes. The important role of miRNAs in inflammation and immune responses is highlighted by studies in which the regulation of miRNAs in the host was shown to be related to infectious diseases and associated with the eradication or susceptibility of the infection. Here, we review the biological aspects of microRNAs, focusing on their roles as regulators of gene expression during pathogen–host interactions and their implications in the immune response against Leishmania, Trypanosoma, Toxoplasma, and Plasmodium infectious diseases.

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Thioester-Containing Protein-4 Regulates the Drosophila Immune Signaling and Function against the Pathogen Photorhabdus

Journal of Innate Immunity ◽

10.1159/000450610 ◽

2016 ◽

Vol 9 (1) ◽

pp. 83-93 ◽

Cited By ~ 23

Author(s):

Upasana Shokal ◽

Ioannis Eleftherianos

Keyword(s):

Immune Response ◽

Photorhabdus Luminescens ◽

Human Pathogen ◽

Loss Of Function ◽

Phenoloxidase Activity ◽

Microbial Infections ◽

Immune Pathways ◽

And Function ◽

Important Progress

Despite important progress in identifying the molecules that participate in the immune response of Drosophila melanogaster to microbial infections, the involvement of thioester-containing proteins (TEPs) in the antibacterial immunity of the fly is not fully clarified. Previous studies mostly focused on identifying the function of TEP2, TEP3 and TEP6 molecules in the D. melanogaster immune system. Here, we investigated the role of TEP4 in the regulation and function of D. melanogaster host defense against 2 virulent pathogens from the genus Photorhabdus, i.e. the insect pathogenic bacterium Photorhabdus luminescens and the emerging human pathogen P. asymbiotica. We demonstrate that Tep4 is strongly upregulated in adult flies following the injection of Photorhabdus bacteria. We also show that Tep4 loss-of-function mutants are resistant to P. luminescens but not to P. asymbiotica infection. In addition, we find that inactivation of Tep4 results in the upregulation of the Toll and Imd immune pathways, and the downregulation of the Jak/Stat and Jnk pathways upon Photorhabdus infection. We document that loss of Tep4 promotes melanization and phenoloxidase activity in the mutant flies infected with Photorhabdus. Together, these findings generate novel insights into the immune role of TEP4 as a regulator and effector of the D. melanogaster antibacterial immune response.

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The Role of Non-Coding RNAs in the Regulation of the Proto-Oncogene MYC in Different Types of Cancer

Biomedicines ◽

10.3390/biomedicines9080921 ◽

2021 ◽

Vol 9 (8) ◽

pp. 921

Author(s):

Ekaterina Mikhailovna Stasevich ◽

Matvey Mikhailovich Murashko ◽

Lyudmila Sergeevna Zinevich ◽

Denis Eriksonovich Demin ◽

Anton Markovich Schwartz

Keyword(s):

Malignant Tumors ◽

Current Data ◽

Cellular Processes ◽

Cell Divisions ◽

Specific Tumor ◽

Different Types ◽

Myc Gene ◽

Non Coding Rnas ◽

Tumor Types

Alterations in the expression level of the MYC gene are often found in the cells of various malignant tumors. Overexpressed MYC has been shown to stimulate the main processes of oncogenesis: uncontrolled growth, unlimited cell divisions, avoidance of apoptosis and immune response, changes in cellular metabolism, genomic instability, metastasis, and angiogenesis. Thus, controlling the expression of MYC is considered as an approach for targeted cancer treatment. Since c-Myc is also a crucial regulator of many cellular processes in healthy cells, it is necessary to find ways for selective regulation of MYC expression in tumor cells. Many recent studies have demonstrated that non-coding RNAs play an important role in the regulation of the transcription and translation of this gene and some RNAs directly interact with the c-Myc protein, affecting its stability. In this review, we summarize current data on the regulation of MYC by various non-coding RNAs that can potentially be targeted in specific tumor types.

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Carboxylesterase overexpression in the male reproductive tract: a universal safeguarding mechanism?

Reproduction Fertility and Development ◽

10.1071/rd99011 ◽

1999 ◽

Vol 11 (3) ◽

pp. 133 ◽

Cited By ~ 16

Author(s):

A. T. Mikhailov ◽

M. Torrado

Keyword(s):

Reproductive Tract ◽

Expression Patterns ◽

Cell Lineage ◽

Environmental Chemicals ◽

Male Reproductive Tract ◽

Morphological Organization ◽

Associated Functions ◽

And Function ◽

Hypothetical Explanation

Data on expression patterns of carboxylesterases in the male reproductive tract of different animal groups (i.e. bivalve mollusks, fruitflies and rodents) are summarized to highlight some particularly interesting questions in the context of sperm differentiation, maturation and function. The male reproduc-tive system, in spite of extreme variation in the anatomical/morphological organization in different species, is characterized by similar patterns of male-dependent carboxylesterase overexpression. The phenomenon of conserved carboxylesterase overexpression indicates similar male sex-associated functions of the enzymes. There is possible evidence of carboxylesterase recruitment by male reproductive-tract tissues indi-cating that it could be adaptive for spermatogenesis, sperm maturation and sperm use. Moreover, this idea can be extended to include a sperm cell lineage protection. This issue is discussed in the light of recent data on environmental reproductive xenobiotics that can provide a basis for a hypothetical explanation of car-boxylesterase overexpression in the male reproductive tract. Based on a well-known role of car-boxylesterases in detoxification of environmental chemicals such as organophosphate pesticides, it is proposed that various male genital tract carboxylesterases may be characterized by a similar physiological function to protect the male reproductive system against xenobiotic influences that could provoke its dys-function, thus altering sperm differentiation and maturation.

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FOXP2 exhibits projection neuron class specific expression, but is not required for multiple aspects of cortical histogenesis

eLife ◽

10.7554/elife.42012 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 6

Author(s):

Ryan J Kast ◽

Alexandra L Lanjewar ◽

Colton D Smith ◽

Pat Levitt

Keyword(s):

Expression Patterns ◽

Projection Neuron ◽

Specific Expression ◽

Neuron Populations ◽

Mouse Cortex ◽

Molecular Studies ◽

Multiple Species ◽

Molecular Phenotypes ◽

And Function

The expression patterns of the transcription factor FOXP2 in the developing mammalian forebrain have been described, and some studies have tested the role of this protein in the development and function of specific forebrain circuits by diverse methods and in multiple species. Clinically, mutations in FOXP2 are associated with severe developmental speech disturbances, and molecular studies indicate that impairment of Foxp2 may lead to dysregulation of genes involved in forebrain histogenesis. Here, anatomical and molecular phenotypes of the cortical neuron populations that express FOXP2 were characterized in mice. Additionally, Foxp2 was removed from the developing mouse cortex at different prenatal ages using two Cre-recombinase driver lines. Detailed molecular and circuit analyses were undertaken to identify potential disruptions of development. Surprisingly, the results demonstrate that Foxp2 function is not required for many functions that it has been proposed to regulate, and therefore plays a more limited role in cortical development than previously thought.

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Substance and Function

What Is A Chemical Element? ◽

10.1093/oso/9780190933784.003.0011 ◽

2020 ◽

pp. 188-203

Author(s):

Jean-Pierre Llored

Keyword(s):

Quantum Chemistry ◽

Philosophy Of Science ◽

Periodic Table ◽

Functional Role ◽

Functional Approach ◽

Different Types ◽

And Function

This paper aims to analyze the two aspects of elements, material and conceptual, in order to further understand the functional role played by elements in chemistry. First, we will refer to how Mendeleev gradually built his periodic table. Second, we will both highlight and reflect upon the functional role of elements in chemistry. In doing so, we will refer in particular to Cassirer’s philosophy of science. In conclusion, we propose that a functional approach is important for understanding current chemical practice, especially in nanochemistry and quantum chemistry. This approach also contributes to the analysis of different types of mereology that coexist in chemistry today.

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The Role of α-Synuclein Oligomers in Parkinson’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms21228645 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8645

Author(s):

Xiao-yu Du ◽

Xi-xiu Xie ◽

Rui-tian Liu

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Theoretical Basis ◽

Critical Role ◽

Treatment Regimens ◽

Propagation Effects ◽

Different Types ◽

Oligomeric Forms ◽

Neurodegeneration Disease

α-synuclein (α-syn) is a protein associated with the pathogenesis of Parkinson’s disease (PD), the second most common neurodegeneration disease with no effective treatment. However, how α-syn drives the pathology of PD remains elusive. Recent studies suggest that α-syn oligomers are the primary cause of neurotoxicity and play a critical role in PD. In this review, we discuss the process of α-syn oligomers formation and the current understanding of the structures of oligomers. We also describe seed and propagation effects of oligomeric forms of α-syn. Then, we summarize the mechanism by which α-syn oligomers exert neurotoxicity and promote neurodegeneration, including mitochondrial dysfunction, endoplasmic reticulum stress, proteostasis dysregulation, synaptic impairment, cell apoptosis and neuroinflammation. Finally, we investigate treatment regimens targeting α-syn oligomers at present. Further research is needed to understand the structure and toxicity mechanism of different types of oligomers, so as to provide theoretical basis for the treatment of PD.

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Expression and Function Studies of CYC/TB1-Like Genes in the Asymmetric Flower Canna (Cannaceae, Zingiberales)

Frontiers in Plant Science ◽

10.3389/fpls.2020.580576 ◽

2020 ◽

Vol 11 ◽

Author(s):

Qianxia Yu ◽

Xueyi Tian ◽

Canjia Lin ◽

Chelsea D. Specht ◽

Jingping Liao

Keyword(s):

Flower Development ◽

Expression Patterns ◽

Asymmetric Distribution ◽

Inflorescence Architecture ◽

Flower Primordia ◽

Fertile Stamen ◽

Spatiotemporal Expression ◽

And Function

The asymmetric flower, lacking any plane of symmetry, is rare among angiosperms. Canna indica L. has conspicuously asymmetric flowers resulting from the presence of a half-fertile stamen, while the other androecial members develop as petaloid staminodes or abort early during development. The molecular basis of the asymmetric distribution of fertility and petaloidy in the androecial whorls remains unknown. Ontogenetic studies have shown that Canna flowers are borne on monochasial (cincinnus) partial florescences within a racemose inflorescence, with floral asymmetry likely corresponding to the inflorescence architecture. Given the hypothesized role of CYC/TB1 genes in establishing floral symmetry in response to the influence of the underlying inflorescence architecture, the spatiotemporal expression patterns of three Canna CYC/TB1 homologs (CiTBL1a, CiTBL1b-1, and CiTBL1b-2) were analyzed during inflorescence and floral development using RNA in situ hybridization and qRT-PCR. In the young inflorescence, both CiTBL1a and CiTBL1b-1 were found to be expressed in the bracts and at the base of the lateral florescence branches, whereas transcripts of CiTBL1b-2 were mainly detected in flower primordia and inflorescence primordia. During early flower development, expression of CiTBL1a and CiTBL1b-1 were both restricted to the developing sepals and petals. In later flower development, expression of CiTBL1a was reduced to a very low level while CiTBL1b-1 was detected with extremely high expression levels in the petaloid androecial structures including the petaloid staminodes, the labellum, and the petaloid appendage of the fertile stamen. In contrast, expression of CiTBL1b-2 was strongest in the fertile stamen throughout flower development, from early initiation of the stamen primordium to maturity of the ½ anther. Heterologous overexpression of CiTBL genes in Arabidopsis led to dwarf plants with smaller petals and fewer stamens, and altered the symmetry of mature flowers. These data provide evidence for the involvement of CYC/TB1 homologs in the development of the asymmetric Cannaceae flower.

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