NOB1: A Potential Biomarker or Target in Cancer

Human NIN1/RPN12 binding protein 1 homolog (NOB1), an RNA binding protein, is expressed ubiquitously in normal tissues such as the lung, liver, and spleen. Its core physiological function is to regulate protease activities and participate in maintaining RNA metabolism and stability. NOB1 is overexpressed in a variety of cancers, including pancreatic cancer, non-small cell lung cancer, ovarian cancer, prostate carcinoma, osteosarcoma, papillary thyroid carcinoma, colorectal cancer, and glioma. Although existing data indicate that NOB1 overexpression is associated with cancer growth, invasion, and poor prognosis, the molecular mechanisms behind these effects and its exact roles remain unclear. Several studies have confirmed that NOB1 is clinically relevant in different cancers, and further research at the molecular level will help evaluate the role of NOB1 in tumors. NOB1 has become an attractive target in anticancer therapy because it is overexpressed in many cancers and mediates different stages of tumor development. Elucidating the role of NOB1 in different signaling pathways as a potential cancer treatment will provide new ideas for existing cancer treatment methods. This review summarizes the research progress made into NOB1 in cancer in the past decade; this information provides valuable clues and theoretical guidance for future anticancer therapy by targeting NOB1.

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Functional Role of Glycosphingolipids in Cancer

Current Medicinal Chemistry ◽

10.2174/0929867327666200831132200 ◽

2020 ◽

Vol 27 ◽

Author(s):

Changping Zheng ◽

Marco Terreni ◽

Matthieu Sollogoub ◽

Yongmin Zhang

Keyword(s):

Cancer Treatment ◽

Tumor Cells ◽

Outer Surface ◽

Crucial Role ◽

Functional Role ◽

Animal Cell ◽

Tumor Development ◽

Normal Tissues ◽

Promising Target

: Glycosphingolipids (GSLs) are ubiquitous components on animal cell membranes, and exposed on the outer surface. Various studies have demonstrated that they play key roles in cells proliferation, adhesion, motility and differentiation. Usually, the specific types of GSLs are expressed more highly in tumors than in normal tissues, which are known as tumorassociated antigens. It has been revealed that most tumor cells show altered GSLs patterns on their surface, abnormal GSLs signaling and biosynthesis, which together play a major role in tumor development. Tumor-associated GSL antigens have been used in the development of antitumor vaccines. It is no doubt that GSLs play a crucial role in tumor progression and would be a promising target for cancer treatment.

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Regulatory Role of microRNAs Targeting the Transcription Co-Factor ZNF521 in Normal Tissues and Cancers

International Journal of Molecular Sciences ◽

10.3390/ijms22168461 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8461

Author(s):

Emanuela Chiarella ◽

Annamaria Aloisio ◽

Stefania Scicchitano ◽

Heather Mandy Bond ◽

Maria Mesuraca

Keyword(s):

Transcription Factor ◽

Molecular Mechanisms ◽

Transitional Cell ◽

Biological Functions ◽

Aberrant Expression ◽

Normal Tissues ◽

Novel Mirna ◽

Mirna Expression Profiling ◽

Mirna Deregulation

Powerful bioinformatics tools have provided a wealth of novel miRNA–transcription factor networks crucial in controlling gene regulation. In this review, we focus on the biological functions of miRNAs targeting ZNF521, explaining the molecular mechanisms by which the dysregulation of this axis contributes to malignancy. ZNF521 is a stem cell-associated co-transcription factor implicated in the regulation of hematopoietic, neural, and mesenchymal stem cells. The aberrant expression of ZNF521 transcripts, frequently associated with miRNA deregulation, has been detected in several tumors including pancreatic, hepatocellular, gastric, bladder transitional cell carcinomas as well as in breast and ovarian cancers. miRNA expression profiling tools are currently identifying a multitude of miRNAs, involved together with oncogenes and TFs in the regulation of oncogenesis, including ZNF521, which may be candidates for diagnostic and prognostic biomarkers of cancer.

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RNA–Binding Protein HuD as a Versatile Factor in Neuronal and Non–Neuronal Systems

Biology ◽

10.3390/biology10050361 ◽

2021 ◽

Vol 10 (5) ◽

pp. 361

Author(s):

Myeongwoo Jung ◽

Eun-Kyung Lee

Keyword(s):

Gene Expression ◽

Neural Plasticity ◽

Molecular Mechanisms ◽

Neuronal Development ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Novel Treatments ◽

Target Mrnas ◽

Neuronal Systems

HuD (also known as ELAVL4) is an RNA–binding protein belonging to the human antigen (Hu) family that regulates stability, translation, splicing, and adenylation of target mRNAs. Unlike ubiquitously distributed HuR, HuD is only expressed in certain types of tissues, mainly in neuronal systems. Numerous studies have shown that HuD plays essential roles in neuronal development, differentiation, neurogenesis, dendritic maturation, neural plasticity, and synaptic transmission by regulating the metabolism of target mRNAs. However, growing evidence suggests that HuD also functions as a pivotal regulator of gene expression in non–neuronal systems and its malfunction is implicated in disease pathogenesis. Comprehensive knowledge of HuD expression, abundance, molecular targets, and regulatory mechanisms will broaden our understanding of its role as a versatile regulator of gene expression, thus enabling novel treatments for diseases with aberrant HuD expression. This review focuses on recent advances investigating the emerging role of HuD, its molecular mechanisms of target gene regulation, and its disease relevance in both neuronal and non–neuronal systems.

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The role of heredity in cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1989.7.4.527 ◽

1989 ◽

Vol 7 (4) ◽

pp. 527-540 ◽

Cited By ~ 19

Author(s):

E G Levine ◽

R A King ◽

C D Bloomfield

Keyword(s):

Molecular Mechanisms ◽

Familial Cancer ◽

Tumor Development ◽

Future Research ◽

Minor Role ◽

Research Activity ◽

Environmental Interactions ◽

Future Research Directions ◽

A Minor

Heredity is generally felt to play a minor role in the development of cancer. This review critically examines this assumption. Topics discussed include evidence for heritable predisposition in animals and humans; the potential importance of genetic-environmental interactions; approaches that are being used to successfully locate genes responsible for heritable predisposition; comparability of genetic findings among heritable and corresponding sporadic malignancies; and future research directions. Breast, colon, and lung cancer are used to exemplify clinical and research activity in familial cancer; clinical phenotypes, segregation and linkage analyses, models for environmental interactions with inherited traits, and molecular mechanisms of tumor development are discussed. We conclude that the contribution of heredity to the cancer burden is greater than generally accepted, and that study of heritable predisposition will continue to reveal carcinogenic mechanisms important to the development of all cancers.

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The Role of Translation Initiation Regulation in Haematopoiesis

Comparative and Functional Genomics ◽

10.1155/2012/576540 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Godfrey Grech ◽

Marieke von Lindern

Keyword(s):

Gene Expression ◽

Translation Initiation ◽

Translational Control ◽

Molecular Mechanisms ◽

Rna Binding ◽

Regulation Of Gene Expression ◽

Mrna Translation ◽

Translation Control ◽

Haematological Disorders

Organisation of RNAs into functional subgroups that are translated in response to extrinsic and intrinsic factors underlines a relatively unexplored gene expression modulation that drives cell fate in the same manner as regulation of the transcriptome by transcription factors. Recent studies on the molecular mechanisms of inflammatory responses and haematological disorders indicate clearly that the regulation of mRNA translation at the level of translation initiation, mRNA stability, and protein isoform synthesis is implicated in the tight regulation of gene expression. This paper outlines how these posttranscriptional control mechanisms, including control at the level of translation initiation factors and the role of RNA binding proteins, affect hematopoiesis. The clinical relevance of these mechanisms in haematological disorders indicates clearly the potential therapeutic implications and the need of molecular tools that allow measurement at the level of translational control. Although the importance of miRNAs in translation control is well recognised and studied extensively, this paper will exclude detailed account of this level of control.

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The RNA-binding protein ELAVL1/HuR is essential for mouse spermatogenesis, acting both at meiotic and postmeiotic stages

Molecular Biology of the Cell ◽

10.1091/mbc.e11-03-0212 ◽

2011 ◽

Vol 22 (16) ◽

pp. 2875-2885 ◽

Cited By ~ 39

Author(s):

Mai Nguyen Chi ◽

Jacques Auriol ◽

Bernard Jégou ◽

Dimitris L. Kontoyiannis ◽

James M.A. Turner ◽

...

Keyword(s):

Germ Cells ◽

Posttranscriptional Regulation ◽

Target Gene ◽

Molecular Mechanisms ◽

Rna Binding ◽

Rna Binding Proteins ◽

Binding Protein ◽

Rna Binding Protein ◽

Female Sterility ◽

Targeted Deletion

Posttranscriptional mechanisms are crucial to regulate spermatogenesis. Accurate protein synthesis during germ cell development relies on RNA binding proteins that control the storage, stability, and translation of mRNAs in a tightly and temporally regulated manner. Here, we focused on the RNA binding protein Embryonic Lethal Abnormal Vision (ELAV) L1/Human antigen R (HuR) known to be a key regulator of posttranscriptional regulation in somatic cells but the function of which during gametogenesis has never been investigated. In this study, we have used conditional loss- and gain-of-function approaches to address this issue in mice. We show that targeted deletion of HuR specifically in germ cells leads to male but not female sterility. Mutant males are azoospermic because of the extensive death of spermatocytes at meiotic divisions and failure of spermatid elongation. The latter defect is also observed upon HuR overexpression. To elucidate further the molecular mechanisms underlying spermatogenesis defects in HuR-deleted and -overexpressing testes, we undertook a target gene approach and discovered that heat shock protein (HSP)A2/HSP70-2, a crucial regulator of spermatogenesis, was down-regulated in both situations. HuR specifically binds hspa2 mRNA and controls its expression at the translational level in germ cells. Our study provides the first genetic evidence of HuR involvement during spermatogenesis and reveals Hspa2 as a target for HuR.

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Critical role of tristetraprolin and AU‐rich element RNA‐binding protein 1 in the suppression of cancer cell growth by globular adiponectin

FEBS Open Bio ◽

10.1002/2211-5463.12541 ◽

2018 ◽

Vol 8 (12) ◽

pp. 1964-1976 ◽

Cited By ~ 1

Author(s):

Nirmala Tilija Pun ◽

Amrita Khakurel ◽

Aastha Shrestha ◽

Sang‐Hyun Kim ◽

Pil‐Hoon Park

Keyword(s):

Cell Growth ◽

Cancer Cell ◽

Rna Binding ◽

Binding Protein ◽

Critical Role ◽

Rna Binding Protein ◽

Cancer Cell Growth ◽

Globular Adiponectin

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The control of inflammation via the phosphorylation and dephosphorylation of tristetraprolin: a tale of two phosphatases

Biochemical Society Transactions ◽

10.1042/bst20160166 ◽

2016 ◽

Vol 44 (5) ◽

pp. 1321-1337 ◽

Cited By ~ 39

Author(s):

Andrew R. Clark ◽

Jonathan L.E. Dean

Keyword(s):

Inflammatory Mediators ◽

Knockout Mouse ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Human Orthologue ◽

And Function ◽

Detailed Picture ◽

Lines Of Evidence

Twenty years ago, the first description of a tristetraprolin (TTP) knockout mouse highlighted the fundamental role of TTP in the restraint of inflammation. Since then, work from several groups has generated a detailed picture of the expression and function of TTP. It is a sequence-specific RNA-binding protein that orchestrates the deadenylation and degradation of several mRNAs encoding inflammatory mediators. It is very extensively post-translationally modified, with more than 30 phosphorylations that are supported by at least two independent lines of evidence. The phosphorylation of two particular residues, serines 52 and 178 of mouse TTP (serines 60 and 186 of the human orthologue), has profound effects on the expression, function and localisation of TTP. Here, we discuss the control of TTP biology via its phosphorylation and dephosphorylation, with a particular focus on recent advances and on questions that remain unanswered.

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Functions of PPR Proteins in Plant Growth and Development

International Journal of Molecular Sciences ◽

10.3390/ijms222011274 ◽

2021 ◽

Vol 22 (20) ◽

pp. 11274

Author(s):

Xiulan Li ◽

Mengdi Sun ◽

Shijuan Liu ◽

Qian Teng ◽

Shihui Li ◽

...

Keyword(s):

Plant Growth ◽

Stress Responses ◽

Rna Processing ◽

Growth And Development ◽

Molecular Mechanisms ◽

Rna Binding ◽

Plant Mitochondria ◽

Research Progress ◽

Plant Growth And Development ◽

Ppr Proteins

Pentatricopeptide repeat (PPR) proteins form a large protein family in land plants, with hundreds of different members in angiosperms. In the last decade, a number of studies have shown that PPR proteins are sequence-specific RNA-binding proteins involved in multiple aspects of plant organellar RNA processing, and perform numerous functions in plants throughout their life cycle. Recently, computational and structural studies have provided new insights into the working mechanisms of PPR proteins in RNA recognition and cytidine deamination. In this review, we summarized the research progress on the functions of PPR proteins in plant growth and development, with a particular focus on their effects on cytoplasmic male sterility, stress responses, and seed development. We also documented the molecular mechanisms of PPR proteins in mediating RNA processing in plant mitochondria and chloroplasts.

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