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The role of noncoding rnas in pituitary adenoma

EPIGENOMICS 2021年第17期13卷 1421-1437页

作者： Bahreini, Farbod Jabbari, Parnian Gossing, Wilhelm Aziziyan, Fatemeh Frohme, Marcus Rezaei, Nima Tarbiat Modares Univ Fac Biol Sci Dept Biochem Tehran Iran Univ Sci Educ & Res Network USERN Malignancy & Autoimmun NIIMA Network Immun Infect Tehran Iran Univ Tehran Med Sci Res Ctr Immunodeficiencies Childrens Med Ctr Tehran Iran Univ Calif Riverside Dept Genet Genom & Bioinformat Riverside CA 92521 USA Tech Univ Appl Sci Wildau Div Mol Biotechnol & Funct Genom Hochschulring 1 D-15745 Wildau Germany Univ Tehran Med Sci Sch Med Dept Immunol Tehran Iran

Pituitary adenomas (PAs) are common cranial tumors that affect the quality of life in patients. Early detection of PA is beneficial for avoiding clinical complications of this disease and increasing the quality of life. noncoding rnas, including long noncoding RNA, miRNA and circRNA, regulate protein expression, mostly by inhibiting the translation process. Studies have shown that dysregulation of noncoding rnas is associated with PA. Hence understanding the expression pattern of noncoding rnas can be considered a promising method for developing biomarkers. This article reviews data on the expression pattern of dysregulated noncoding rnas involved in PA. Possible molecular mechanisms by which the dysregulated noncoding RNA could possibly induce PA are also described. Lay abstract Pituitary adenomas (PA) are benign, slow-growing tumors of the pituitary gland. The sooner the tumor is diagnosed, the sooner can the patient be treated with medication. The early detection of this disease can reduce the need for surgery to remove the tumor. noncoding rnas are small molecules that regulate the functions and behavior of different cells. When the intracellular or extracellular concentration of these small molecules is altered, the functions and behavior of cells and tissues can be affected and changed. Quantifying and analyzing these molecules is a promising tool for the early detection of different diseases, including PA. This article reviews alterations in these small molecules and the relationship between these alterations and the incidence of PA.

关键词： biotechnology noncoding rnas pituitary neoplasms tumor biomarker

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Role of transcription factors, noncoding rnas, epitranscriptomics, and epigenetics in post-ischemic neuroinflammation

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JOURNAL OF NEUROCHEMISTRY 2024年第10期168卷 3430-3448页

作者： Mehta, Suresh L. Arruri, Vijay Vemuganti, Raghu Univ Wisconsin Dept Neurol Surg Madison WI USA William S Middleton Vet Hosp Madison WI USA Univ Wisconsin Dept Neurol Surg 600 Highland Ave Madison WI 53792 USA

Post-stroke neuroinflammation is pivotal in brain repair, yet persistent inflammation can aggravate ischemic brain damage and hamper recovery. Following stroke, specific molecules released from brain cells attract and activate central and peripheral immune cells. These immune cells subsequently release diverse inflammatory molecules within the ischemic brain, initiating a sequence of events, including activation of transcription factors in different brain cell types that modulate gene expression and influence outcomes;the interactive action of various noncoding rnas (ncrnas) to regulate multiple biological processes including inflammation, epitranscriptomic RNA modification that controls RNA processing, stability, and translation;and epigenetic changes including DNA methylation, hydroxymethylation, and histone modifications crucial in managing the genic response to stroke. Interactions among these events further affect post-stroke inflammation and shape the depth of ischemic brain damage and functional outcomes. We highlighted these aspects of neuroinflammation in this review and postulate that deciphering these mechanisms is pivotal for identifying therapeutic targets to alleviate post-stroke dysfunction and enhance recovery.

关键词： brain damage gene expression neuroinflammation noncoding rnas stroke

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Identification and function annotation of long intervening noncoding rnas

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BRIEFINGS IN BIOINFORMATICS 2017年第5期18卷 789-797页

作者： Luo, Haitao Bu, Dechao Sun, Liang Fang, Shuangsang Liu, Zhiyong Zhao, Yi Chinese Acad Sci Key Lab Intelligent Informat Proc Inst Comp Technol Beijing 100190 Peoples R China Chinese Acad Sci Precis Med Ctr Res Inst Informat Ind LuoYang LuoYang BranchInst Comp Technol Luoyang 471000 Peoples R China Univ Chinese Acad Sci Beijing 100190 Peoples R China Chinese Acad Sci Inst Comp Technol Adv Comp Res Ctr Beijing Peoples R China

RNA-seq technology offers the promise of rapid comprehensive discovery of long intervening noncoding rnas (lincrnas). Basic tools such as Tophat and Cufflinks have been widely used for RNA-seq assembly. However, advanced bioinformatics methodologies that allow in-depth analysis of lincrnas are lacking. Here, we describe a computational protocol that is especially designed for the identification of novel lincrnas and the prediction of the function. The protocol mainly includes two open-access tools, CNCI and ncFANs. CNCI allows users to distinguish noncoding from protein-coding transcripts and to retrieve novel lincrnas. ncFANs integrates expression profiles of protein-coding and lincRNA genes to construct co-expression networks. Such networks are subsequently used to perform function predictions of unknown lincrnas. This protocol will allow users to apply these procedures without the need of additional training. All the tools in current protocol are available http://***/np/.

关键词： transcriptom sequencing noncoding rnas gene identification function annotation network analysis computational method

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Serum exosomal long noncoding rnas as a diagnostic biomarker for atrial fibrillation

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HEART RHYTHM 2022年第9期19卷 1450-1458页

作者： Kang, Ji-Young Mun, Dasom Kim, Hyoeun Yun, Nuri Joung, Boyoung Yonsei Univ Coll Med Div Cardiol Seoul South Korea Yonsei Univ Coll Med Dept Biochem & Mol Biol Seoul South Korea Yonsei Univ Inst Life Sci & Biotechnol Seoul South Korea

BACKGROUND Exosomal long noncoding rnas (lncrnas) are known as ideal diagnostic biomarkers of various diseases. However, there are no reports on the use of serum exosomal lncrnas as diagnostic biomarkers for atrial fibrillation (AF). OBJECTIVE The purpose of this study was to explore serum exosomal lncrnas as a useful tool for diagnosing AF. METHODS Serum exosomes from patients with persistent AF and controls were isolated using a polymer-based exosome precipitation kit. We conducted a multiphase process including screening and 2 independent validation phases. In the screening phase, serum exosomal lncRNA expression profiles were examined using RNA sequencing analysis. In 2 validation phases, we evaluated the expression levels of candidate exosomal lncrnas using quantitative reverse transcription polymerase chain reaction. Finally, we performed different statistical and functional analyses. RESULTS After the screening phase, we identified 26 differentially expressed lncrnas (ie, 15 upregulated and 11 downregulated lncrnas with a jfold changej >= 2 and P <.05) in serum exosomes from patients with persistent AF compared with controls. We then screened out 6 exosomal lncrnas as biomarker candidates following parameters: read length >= 200 nucleotides;exon number >= 2;and coding potential score < 0.1. In 2 validation phases, exosomal lncrnas LOC105377989 and LOC107986997 were consistently upregulated in the serum of patients with persistent AF compared with controls (P < 0001). Moreover, both exosomal lncrnas exhibited significant diagnostic validity for AF. Notably, exosomal lncRNA LOC107986997 was involved in AF-related pathophysiological mechanisms. CONCLUSION Serum-derived exosomal lncRNA LOC107986997 could serve as a potential biomarker for AF diagnosis.

关键词： Atrial fibrillation Biomarker Diagnosis Exosome Long noncoding rnas

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Interaction between N⁶-methyladenosine (m⁶A) modification and noncoding rnas in cancer

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MOLECULAR CANCER 2020年第1期19卷 1-14页

作者： Chen, Yi Lin, Yu Shu, Yongqian He, Jing Gao, Wen Nanjing Med Univ Affiliated Hosp 1 Dept Oncol 300 Guangzhou Rd Nanjing 210029 Peoples R China

As a critical internal RNA modification in higher eukaryotes, N-6-methyladenosine (m(6)A) has become the hotspot of epigenetics research in recent years. Extensive studies on messenger rnas have revealed that m(6)A affects RNA fate and cell functions in various bioprocesses, such as RNA splicing, export, translation, and stability, some of which seem to be directly or indirectly regulated by noncoding rnas. Intriguingly, abundant noncoding rnas such as micrornas, long noncoding rnas, circular rnas, small nuclear rnas, and ribosomal rnas are also highly modified with m(6)A and require m(6)A modification for their biogenesis and functions. Here, we discuss the interaction between m(6)A modification and noncoding rnas by focusing on the functional relevance of m(6)A in cancer progression, metastasis, drug resistance, and immune response. Furthermore, the investigation of m(6)A regulatory proteins and its inhibitors provides new opportunities for early diagnosis and effective treatment of cancer, especially in combination with immunotherapy.

关键词： m(6)A modification noncoding rnas Cancer

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Long-noncoding rnas in basal cell carcinoma

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TUMOR BIOLOGY 2016年第8期37卷 10595-10608页

作者： Sand, Michael Bechara, Falk G. Sand, Daniel Gambichler, Thilo Hahn, Stephan A. Bromba, Michael Stockfleth, Eggert Hessam, Schapoor Ruhr Univ Bochum Dept Dermatol Venereol & Allergol Dermatol Surg Unit D-44791 Bochum Germany St Josef Hosp Catholic Clin Ruhr Peninsula Dept Plast Surg D-45257 Essen Germany Univ Michigan Kellogg Eye Ctr Ann Arbor MI 48105 USA Knappschaftskrankenhaus Univ Bochum Zentrum Klin Forsch Dept Internal Med Lab Mol Gastroenterol Onkol D-44780 Bochum Germany

Long noncoding rnas (lncrnas) are fundamental regulators of pre- and post-transcriptional gene regulation. Over 35,000 different lncrnas have been described with some of them being involved in cancer formation. The present study was initiated to describe differentially expressed lncrnas in basal cell carcinoma (BCC). Patients with BCC (n = 6) were included in this study. Punch biopsies were harvested from the tumor center and nonlesional epidermal skin (NLES, control, n = 6). Microarray-based lncRNA and mRNA expression profiles were identified through screening for 30,586 lncrnas and 26,109 protein-coding transcripts (mrnas). The microarray data were validated by RT-PCR in a second set of BCC versus control samples. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of mrnas were performed to assess biologically relevant pathways. A total of 1851 lncrnas were identified as being significantly up-regulated, whereas 2165 lncrnas were identified as being significantly down-regulated compared to nonlesional skin (p < 0.05). Oncogenic and/or epidermis-specific lncrnas, such as CASC15 or ANRIL, were among the differentially expressed sequences. GO analysis showed that the highest enriched GO targeted by up-regulated transcripts was "extracellular matrix." KEGG pathway analysis showed the highest enrichment scores in "Focal adhesion." BCC showed a significantly altered lncRNA and mRNA expression profile. Dysregulation of previously described lncrnas may play a role in the molecular pathogenesis of BCC and should be subject of further analysis.

关键词： Long noncoding rnas Basal cell carcinoma noncoding rnas Epithelial skin cancer Nonmelanoma skin cancer

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Exosomal micrornas and long noncoding rnas: as novel biomarkers for endometriosis

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CELL AND TISSUE RESEARCH 2023年第1期394卷 55-74页

作者： Soltani-Fard, Elahe Asadi, Marzieh Taghvimi, Sina Vafadar, Asma Vosough, Parisa Tajbakhsh, Amir Savardashtaki, Amir Shahrekord Univ Med Sci Sch Adv Technol Dept Mol Med Shahrekord Iran Shiraz Univ Med Sci Sch Adv Med Sci & Technol Dept Med Biotechnol Shiraz *** Iran Shahid Chamran Univ Ahvaz Fac Sci Dept Biol Ahvaz Iran Shiraz Univ Med Sci Student Res Comm Shiraz Iran Shiraz Univ Med Sci Pharmaceut Sci Res Ctr Shiraz Iran Shiraz Univ Med Sci Sch Adv Med Sci & Technol Dept Mol Med Shiraz Iran Shiraz Univ Med Sci Infertil Res Ctr Shiraz Iran

Endometriosis is a gynecological inflammatory disorder characterized by the development of endometrial-like cells outside the uterine cavity. This disease is associated with a wide range of clinical presentations, such as debilitating pelvic pain and infertility issues. Endometriosis diagnosis is not easily discovered by ultrasound or clinical examination. Indeed, difficulties in noninvasive endometriosis diagnosis delay the confirmation and management of the disorder, increase symptoms, and place a significant medical and financial burden on patients. So, identifying specific and sensitive biomarkers for this disease should therefore be a top goal. Exosomes are extracellular vesicles secreted by most cell types. They transport between cells' bioactive molecules such as noncoding rnas and proteins. Micrornas and long noncoding rnas which are key molecules transferred by exosomes have recently been identified to have a significant role in endometriosis by modulating different proteins and their related genes. As a result, the current review focuses on exosomal micro-and-long noncoding rnas that are involved in endometriosis disease. Furthermore, major molecular mechanisms linking corresponding RNA molecules to endometriosis development will be briefly discussed to better clarify the potential functions of exosomal noncoding rnas in the therapy and diagnosis of endometriosis.

关键词： Endometriosis Exosome Exosomal long noncoding rnas Exosomal micrornas noncoding rnas

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Modulation of long noncoding rnas by polyphenols as a novel potential therapeutic approach in lung cancer: A comprehensive review

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PHYTOTHERAPY RESEARCH 2024年第6期38卷 3240-3267页

作者： Lv, Hong Qian, Dawei Xu, Shuhua Fan, Guiqin Qian, Qiuhong Cha, Dongsheng Qian, Xingjia Zhou, Guoping Lu, Bing Taicang TCM Hosp Dept Pulm & Crit Care Med Taicang 215499 Jiangsu Peoples R China Tongling Yian Dist Peoples Hosp Dept Thorac Surg Tongling Peoples R China Dongtai Hosp Tradit Chinese Med Dept Cardiothorac Surg Dongtai 224221 Peoples R China

Lung cancer stands as a formidable global health challenge, necessitating innovative therapeutic strategies. Polyphenols, bioactive compounds synthesized by plants, have garnered attention for their diverse health benefits, particularly in combating various cancers, including lung cancer. The advent of whole-genome and transcriptome sequencing technologies has illuminated the pivotal roles of long noncoding rnas (lncrnas), operating at epigenetic, transcriptional, and posttranscriptional levels, in cancer progression. This review comprehensively explores the impact of polyphenols on both oncogenic and tumor-suppressive lncrnas in lung cancer, elucidating on their intricate regulatory mechanisms. The comprehensive examination extends to the potential synergies when combining polyphenols with conventional treatments like chemotherapy, radiation, and immunotherapy. Recognizing the heterogeneity of lung cancer subtypes, the review emphasizes the need for the integration of nanotechnology for optimized polyphenol delivery and personalized therapeutic approaches. In conclusion, we collect the latest research, offering a holistic overview of the evolving landscape of polyphenol-mediated modulation of lncrnas in lung cancer therapy. The integration of polyphenols and lncrnas into multidimensional treatment strategies holds promise for enhancing therapeutic efficacy and navigating the challenges associated with lung cancer treatment.

关键词： epigenetic long noncoding RNA lung cancer noncoding rnas polyphenols therapy

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Tumor microenvironment and noncoding rnas as co-drivers of epithelial-mesenchymal transition and cancer metastasis

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DEVELOPMENTAL DYNAMICS 2018年第3期247卷 405-431页

作者： Alsibai, Kinan Drak Meseure, Didier Le Raincy Montfermeil Hosp Dept Pathol 10 Rue Gen Leclerc F-93370 Montfermeil France Curie Inst Platform Invest Pathol Paris France Curie Inst Dept Pathol Paris France

Reciprocal interactions between cancer cells and tumor microenvironment (TME) are crucial events in tumor progression and metastasis. Pervasive stromal reprogramming of TME modifies numerous cellular functions, including extracellular matrix (ECM) stiffness, inflammation, and immunity. These environmental factors allow selection of more aggressive cells that develop adaptive strategies associating plasticity and epithelial-mesenchymal transition (EMT), stem-like phenotype, invasion, immunosuppression, and resistance to therapies. EMT is a morphomolecular process that endows epithelial tumor cells with mesenchymal properties, including reduced adhesion and increased motility. Numerous studies have demonstrated involvement of noncoding rnas (ncrnas), such as mirnas and lncrnas, in tumor initiation, progression, and metastasis. Ncrnas regulate every hallmark of cancer and have now emerged as new players in induction and regulation of EMT. The reciprocal regulatory interactions between ncrnas, TME components, and cancer cells increase the complexity of gene expression and protein translation in cancer. Thus, deeper understanding of molecular mechanisms controlling EMT will not only shed light on metastatic processes of cancer cells, but enhance development of new therapies targeting metastasis. In this review, we will provide recent findings on the role of known ncrnas relevant to EMT and cancer metastasis and discuss the role of the interaction between ncrnas and TME as co-drivers of EMT. Developmental Dynamics 247:405-431, 2018. (c) 2017 Wiley Periodicals, Inc.

关键词： cancer cells tumor microenvironment micrornas noncoding rnas Lncrnas extracellular matrix ECM epithelial-mesenchymal transition EMT

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Intricate crosstalk between MYB and noncoding rnas in cancer

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CANCER CELL INTERNATIONAL 2021年第1期21卷 1-15页

作者： Hu, Dingyu Shao, Wenjun Liu, Li Wang, Yanyan Yuan, Shunling Liu, Zhaoping Liu, Jing Zhang, Ji Univ South China Affiliated Hosp 1 Hengyang Med Sch Dept Rheumatol Hengyang 421001 Hunan Peoples R China Cent South Univ Mol Biol Res Ctr Sch Life Sci Hunan Prov Key Lab Basic & Appl Hematol Changsha 410078 Hunan Peoples R China Cent South Univ Ctr Med Genet Sch Life Sci Changsha 410078 Hunan Peoples R China Shenzhen Tradit Chinese Med Hosp Dept Clin Lab Shenzhen 518033 Guangdong Peoples R China

MYB is often overexpressed in malignant tumors and plays a carcinogenic role in the initiation and development of cancer. Deletion of the MYB regulatory C-terminal domain may be a driving mutation leading to tumorigenesis, therefore, different tumor mechanisms produce similar MYB proteins. As MYB is a transcription factor, priority has been given to identifying the genes that it regulates. All previous attention has been focused on protein-coding genes. However, an increasing number of studies have suggested that MYB can affect the complexity of cancer progression by regulating tumor-associated noncoding rnas (ncrnas), such as micrornas, long-non-coding rnas and circular rnas. ncrnas can regulate the expression of numerous downstream genes at the transcription, RNA processing and translation levels, thereby having various biological functions. Additionally, ncrnas play important roles in regulating MYB expression. This review focuses on the intricate crosstalk between oncogenic MYB and ncrnas, which play a pivotal role in tumorigenesis, including proliferation, apoptosis, angiogenesis, metastasis, senescence and drug resistance. In addition, we discuss therapeutic strategies for crosstalk between MYB and ncrnas to prevent the occurrence and development of cancer.

关键词： MYB noncoding rnas Lncrnas Mirnas Tumorigenesis

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