Long Noncoding RNAs: Recent Insights into Their Role in Male Infertility and Their Potential as Biomarkers and Therapeutic Targets

Long noncoding RNAs (lncRNAs) are composed of nucleotides located in the nucleus and cytoplasm; these are transcribed by RNA polymerase II and are greater than 200 nt in length. LncRNAs fulfill important functions in a variety of biological processes, including genome imprinting, cell differentiation, apoptosis, stem cell pluripotency, X chromosome inactivation and nuclear transport. As high throughput sequencing technology develops, a substantial number of lncRNAs have been found to be related to a variety of biological processes, such as development of the testes, maintaining the self-renewal and differentiation of spermatogonial stem cells, and regulating spermatocyte meiosis. These indicate that lncRNAs can be used as biomarkers and potential therapeutic targets for male infertility. However, only a few comprehensive reviews have described the role of lncRNAs in male reproduction. In this paper, we summarize recent findings relating to the role of lncRNAs in spermatogenesis, their potential as biomarkers for male infertility and the relationship between reproductive arrest and transgenerational effects. Finally, we suggest specific targets for the treatment of male infertility from the perspective of lncRNAs.

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Long Noncoding RNAs and Their Therapeutic Promise in Diabetic Nephropathy

Nephron ◽

10.1159/000515422 ◽

2021 ◽

pp. 1-11

Author(s):

Juan D. Coellar ◽

Jianyin Long ◽

Farhad R. Danesh

Keyword(s):

Diabetic Nephropathy ◽

Large Scale ◽

Kidney Diseases ◽

Noncoding Rnas ◽

Therapeutic Targets ◽

Long Noncoding Rnas ◽

Biological Processes ◽

Aberrant Expression ◽

Genome Wide

Recent advances in large-scale RNA sequencing and genome-wide profiling projects have unraveled a heterogeneous group of RNAs, collectively known as long noncoding RNAs (lncRNAs), which play central roles in many diverse biological processes. Importantly, an association between aberrant expression of lncRNAs and diverse human pathologies has been reported, including in a variety of kidney diseases. These observations have raised the possibility that lncRNAs may represent unexploited potential therapeutic targets for kidney diseases. Several important questions regarding the functionality of lncRNAs and their impact in kidney diseases, however, remain to be carefully addressed. Here, we provide an overview of the main functions and mechanisms of actions of lncRNAs, and their promise as therapeutic targets in kidney diseases, emphasizing on the role of some of the best-characterized lncRNAs implicated in the pathogenesis and progression of diabetic nephropathy.

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Transcriptional profiling of long noncoding RNAs associated with leaf-color mutation in Ginkgo biloba L

BMC Plant Biology ◽

10.1186/s12870-019-2141-z ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 3

Author(s):

Yaqiong Wu ◽

Jing Guo ◽

Tongli Wang ◽

Fuliang Cao ◽

Guibin Wang

Keyword(s):

Ginkgo Biloba ◽

High Throughput Sequencing ◽

Target Genes ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Differentially Expressed ◽

Biological Processes ◽

Leaf Color ◽

Wide Range ◽

Color Mutation

Abstract Background Long noncoding RNAs (lncRNAs) play an important role in diverse biological processes and have been widely studied in recent years. However, the roles of lncRNAs in leaf pigment formation in ginkgo (Ginkgo biloba L.) remain poorly understood. Results In this study, lncRNA libraries for mutant yellow-leaf and normal green-leaf ginkgo trees were constructed via high-throughput sequencing. A total of 2044 lncRNAs were obtained with an average length of 702 nt and typically harbored 2 exons. We identified 238 differentially expressed lncRNAs (DELs), 32 DELs and 49 differentially expressed mRNAs (DEGs) that constituted coexpression networks. We also found that 48 cis-acting DELs regulated 72 target genes, and 31 trans-acting DELs regulated 31 different target genes, which provides a new perspective for the regulation of the leaf-color mutation. Due to the crucial regulatory roles of lncRNAs in a wide range of biological processes, we conducted in-depth studies on the DELs and their targets and found that the chloroplast thylakoid membrane subcategory and the photosynthesis pathways (ko00195) were most enriched, suggesting their potential roles in leaf coloration mechanisms. In addition, our correlation analysis indicates that eight DELs and 68 transcription factors (TFs) might be involved in interaction networks. Conclusions This study has enriched the knowledge concerning lncRNAs and provides new insights into the function of lncRNAs in leaf-color mutations, which will benefit future selective breeding of ginkgo.

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Role of Long Noncoding RNAs in Parkinson’s Disease: Putative Biomarkers and Therapeutic Targets

Parkinson s Disease ◽

10.1155/2020/5374307 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Qiankun Lv ◽

Ziyu Wang ◽

Zhen Zhong ◽

Wei Huang

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Noncoding Rnas ◽

Therapeutic Targets ◽

Alpha Synuclein ◽

Long Noncoding Rnas ◽

Main Risk Factor ◽

Diagnostic Biomarkers ◽

Rna Molecules

Parkinson’s disease (PD) is a neurodegenerative disease characterized by bradykinesia, rigidity, and tremor. Age is the main risk factor. Long noncoding RNAs (lncRNAs) are novel RNA molecules of more than 200 nucleotides in length. They may be involved in the regulation of many pathological processes of PD. PD has a variety of pathophysiological mechanisms, including alpha-synuclein aggregate, mitochondrial dysfunction, oxidative stress, calcium homeostasis, axonal transport, and neuroinflammation. Among these, the impacts of lncRNAs on the pathogenesis and progression of PD need to be highlighted. lncRNAs may serve as putative biomarkers and therapeutic targets for the early diagnosis of PD. This study aimed to investigate the role of lncRNAs in various pathological processes of PD and the specific lncRNAs that might be used as putative diagnostic biomarkers and therapeutic targets of PD.

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Emerging Role of Exosomal-Derived Long Noncoding RNAs in Human PDAC

Visceral Medicine ◽

10.1159/000520947 ◽

2021 ◽

pp. 1-7

Author(s):

Di Long ◽

Xiao Dong Tian ◽

Yin-Mo Yang

Keyword(s):

Early Diagnosis ◽

Prognostic Markers ◽

Noncoding Rnas ◽

Therapeutic Targets ◽

Long Noncoding Rnas ◽

Current Status ◽

Ductal Adenocarcinoma ◽

Advanced Stage ◽

Incidence And Mortality

Background: The incidence and mortality of pancreatic ductal adenocarcinoma (PDAC) are increasing recently. Most patients with PDAC are diagnosed at advanced stage because of the high invasiveness of cancer cells and the lack of typical early symptoms. Therefore, early diagnosis of PDAC is very important to improve the prognosis. Exosomes play crucial role in intercellular communication and deliver the contents to recipient cells to regulate their biological behaviors. Recent evidence suggests emerging role of exosomes in the carcinogenesis of a variety of cancers including PDAC. Long noncoding RNAs (LncRNAs) have been reported to be involved in the development of PDAC. It has been proved that LncRNAs have the potential to be biomarkers and therapeutic targets for PDAC. Moreover, increasing number of studies focus on the role of exosomal LncRNAs in PDAC. Summary: In this review, we summarize the current status on our understanding of the role of exosomal-derived LncRNAs in the progression and metastasis of PDAC. Key Messages: We focus on challenges in the potential of exosomal-derived LncRNAs as novel diagnostic and prognostic markers and therapeutic targets of PDAC. In addition, we provide an overview about the demonstrated important role of exosomal LncRNAs in the progression of PDAC.

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The Role of lncRNA in the Development of Tumors, Including Breast Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22168427 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8427

Author(s):

Beata Smolarz ◽

Anna Zadrożna-Nowak ◽

Hanna Romanowicz

Keyword(s):

Breast Cancer ◽

Breast Carcinoma ◽

Present Article ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Regulation Of Transcription ◽

Ribonucleic Acids ◽

Detailed Review ◽

Cellular Processes

Long noncoding RNAs (lncRNAs) are the largest groups of ribonucleic acids, but, despite the increasing amount of literature data, the least understood. Given the involvement of lncRNA in basic cellular processes, especially in the regulation of transcription, the role of these noncoding molecules seems to be of great importance for the proper functioning of the organism. Studies have shown a relationship between disturbed lncRNA expression and the pathogenesis of many diseases, including cancer. The present article presents a detailed review of the latest reports and data regarding the importance of lncRNA in the development of cancers, including breast carcinoma.

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Genome-Wide Identification and Characterization of Long Noncoding RNAs Involved in Chinese Wheat Mosaic Virus Infection of Nicotiana benthamiana

Biology ◽

10.3390/biology10030232 ◽

2021 ◽

Vol 10 (3) ◽

pp. 232

Author(s):

Weiran Zheng ◽

Haichao Hu ◽

Qisen Lu ◽

Peng Jin ◽

Linna Cai ◽

...

Keyword(s):

Virus Infection ◽

Mosaic Virus ◽

Nicotiana Benthamiana ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Differentially Expressed ◽

Genome Wide ◽

Chinese Wheat

Recent studies have shown that a large number of long noncoding RNAs (lncRNAs) can regulate various biological processes in animals and plants. Although lncRNAs have been identified in many plants, they have not been reported in the model plant Nicotiana benthamiana. Particularly, the role of lncRNAs in plant virus infection remains unknown. In this study, we identified lncRNAs in N. benthamiana response to Chinese wheat mosaic virus (CWMV) infection by RNA sequencing. A total of 1175 lncRNAs, including 65 differentially expressed lncRNAs, were identified during CWMV infection. We then analyzed the functions of some of these differentially expressed lncRNAs. Interestingly, one differentially expressed lncRNA, XLOC_006393, was found to participate in CWMV infection as a precursor to microRNAs in N. benthamiana. These results suggest that lncRNAs play an important role in the regulatory network of N. benthamiana in response to CWMV infection.

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The Role of Long Noncoding RNAs in Diabetic Alzheimer’s Disease

Journal of Clinical Medicine ◽

10.3390/jcm7110461 ◽

2018 ◽

Vol 7 (11) ◽

pp. 461 ◽

Cited By ~ 4

Author(s):

Young-Kook Kim ◽

Juhyun Song

Keyword(s):

Alzheimer’S Disease ◽

Insulin Resistance ◽

Alzheimer's Disease ◽

Neurodegenerative Diseases ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Glucose Dysregulation ◽

Near Future ◽

The Brain

Long noncoding RNAs (lncRNAs) are involved in diverse physiological and pathological processes by modulating gene expression. They have been found to be dysregulated in the brain and cerebrospinal fluid of patients with neurodegenerative diseases, and are considered promising therapeutic targets for treatment. Among the various neurodegenerative diseases, diabetic Alzheimer’s disease (AD) has been recently emerging as an important issue due to several unexpected reports suggesting that metabolic issues in the brain, such as insulin resistance and glucose dysregulation, could be important risk factors for AD. To facilitate understanding of the role of lncRNAs in this field, here we review recent studies on lncRNAs in AD and diabetes, and summarize them with different categories associated with the pathogenesis of the diseases including neurogenesis, synaptic dysfunction, amyloid beta accumulation, neuroinflammation, insulin resistance, and glucose dysregulation. It is essential to understand the role of lncRNAs in the pathogenesis of diabetic AD from various perspectives for therapeutic utilization of lncRNAs in the near future.

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Oncogenic Role of Exosomal Circular and Long Noncoding RNAs in Gastrointestinal Cancers

International Journal of Molecular Sciences ◽

10.3390/ijms23020930 ◽

2022 ◽

Vol 23 (2) ◽

pp. 930

Author(s):

Ba Da Yun ◽

Ye Ji Choi ◽

Seung Wan Son ◽

Gabriel Adelman Cipolla ◽

Fernanda Costa Brandão Berti ◽

...

Keyword(s):

Epithelial To Mesenchymal Transition ◽

Cell Communication ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Circular Rnas ◽

Gastrointestinal Cancers ◽

Gastrointestinal Malignancies ◽

Mesenchymal Transition ◽

Novel Therapeutic Strategies

Circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) are differentially expressed in gastrointestinal cancers. These noncoding RNAs (ncRNAs) regulate a variety of cellular activities by physically interacting with microRNAs and proteins and altering their activity. It has also been suggested that exosomes encapsulate circRNAs and lncRNAs in cancer cells. Exosomes are then discharged into the extracellular environment, where they are taken up by other cells. As a result, exosomal ncRNA cargo is critical for cell–cell communication within the cancer microenvironment. Exosomal ncRNAs can regulate a range of events, such as angiogenesis, metastasis, immune evasion, drug resistance, and epithelial-to-mesenchymal transition. To set the groundwork for developing novel therapeutic strategies against gastrointestinal malignancies, a thorough understanding of circRNAs and lncRNAs is required. In this review, we discuss the function and intrinsic features of oncogenic circRNAs and lncRNAs that are enriched within exosomes.

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