scholarly journals Mrhl Long Noncoding RNA Mediates Meiotic Commitment of Mouse Spermatogonial Cells by Regulating Sox8 Expression

2017 ◽  
Vol 37 (14) ◽  
Author(s):  
Shubhangini Kataruka ◽  
Vijay Suresh Akhade ◽  
Bhavana Kayyar ◽  
Manchanahalli R. Satyanarayana Rao
Keyword(s):  
Wnt Signaling ◽  
Germ Cells ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Stem Cell Markers ◽  
Biological Processes ◽  
Meiotic Progression ◽  
Regulatory Link ◽  
Regulatory Loop ◽  
Signaling Activation

ABSTRACT Long noncoding RNAs (lncRNAs) are important regulators of various biological processes, including spermatogenesis. Our previous studies have revealed the regulatory loop of mrhl RNA and Wnt signaling, where mrhl RNA negatively regulates Wnt signaling and gets downregulated upon Wnt signaling activation. This downregulation of mrhl RNA is important for the meiotic progression of spermatogonial cells. In our present study, we identified the transcription factor Sox8 as the regulatory link between mrhl RNA expression, Wnt signaling activation, and meiotic progression. In contrast to reports from other groups, we report the expression of Sox8 in germ cells and describe the molecular mechanism of Sox8 regulation by mrhl RNA during differentiation of spermatogonial cells. Binding of mrhl RNA to the Sox8 promoter is accompanied by the assembly of other regulatory factors involving Myc-Max-Mad transcription factors, corepressor Sin3a, and coactivator Pcaf. In the context of Wnt signaling, Sox8 directly regulates the expression of premeiotic and meiotic markers. Prolonged Wnt signaling activation in spermatogonial cells leads to changes in global chromatin architecture and a decrease in levels of stem cell markers.

scholarly journals Long Noncoding RNA: Regulatory Mechanisms and Therapeutic Potential in Sepsis

2021 ◽  
Vol 11 ◽  
Author(s):  
Wei Wang ◽  
Ni Yang ◽  
Ri Wen ◽  
Chun-Feng Liu ◽  
Tie-Ning Zhang
Keyword(s):  
Host Response ◽  
Noncoding Rna ◽  
Therapeutic Potential ◽  
Noncoding Rnas ◽  
Specific Treatment ◽  
Kidney Injury ◽  
Biological Processes ◽  
Immune Functions ◽  
Life Threatening ◽  
Organ Dysfunctions

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and is characterized by a hyperinflammatory state accompanied by immunosuppression. Long noncoding RNAs (lncRNAs) are noncoding RNAs longer than 200 nucleotides and have important roles in mediating various biological processes. Recently, lncRNAs were found to exert both promotive and inhibitory immune functions in sepsis, thus participating in sepsis regulation. Additionally, several studies have revealed that lncRNAs are involved in sepsis-induced organ dysfunctions, including cardiovascular dysfunction, acute lung injury, and acute kidney injury. Considering the lack of effective biomarkers for early identification and specific treatment for sepsis, lncRNAs may be promising biomarkers and even targets for sepsis therapies. This review systematically highlights the recent advances regarding the roles of lncRNAs in sepsis and sheds light on their use as potential biomarkers and treatment targets for sepsis.

scholarly journals Of rodents and ruminants: a comparison of small noncoding RNA requirements in mouse and bovine reproduction

2021 ◽  
Vol 99 (3) ◽  
Author(s):  
Lauren G Chukrallah ◽  
Aditi Badrinath ◽  
Kelly Seltzer ◽  
Elizabeth M Snyder
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Noncoding Rna ◽  
Reproductive Potential ◽  
Noncoding Rnas ◽  
Model Organism ◽  
Cell Physiology ◽  
Male Germ Cells ◽  
Small Noncoding Rna ◽  
Small Noncoding Rnas

Abstract Ruminants are major producers of meat and milk, thus managing their reproductive potential is a key element in cost-effective, safe, and efficient food production. Of particular concern, defects in male germ cells and female germ cells may lead to significantly reduced live births relative to fertilization. However, the underlying molecular drivers of these defects are unclear. Small noncoding RNAs, such as piRNAs and miRNAs, are known to be important regulators of germ-cell physiology in mouse (the best-studied mammalian model organism) and emerging evidence suggests that this is also the case in a range of ruminant species, in particular bovine. Similarities exist between mouse and bovids, especially in the case of meiotic and postmeiotic male germ cells. However, fundamental differences in small RNA abundance and metabolism between these species have been observed in the female germ cell, differences that likely have profound impacts on their physiology. Further, parentally derived small noncoding RNAs are known to influence early embryos and significant species-specific differences in germ-cell born small noncoding RNAs have been observed. These findings demonstrate the mouse to be an imperfect model for understanding germ-cell small noncoding RNA biology in ruminants and highlight the need to increase research efforts in this underappreciated aspect of animal reproduction.

The mechanistic, diagnostic and therapeutic novel nucleic acids for hepatocellular carcinoma emerging in past score years

2020 ◽  
Author(s):  
Song Zhang ◽  
Ying Zhou ◽  
Yanan Wang ◽  
Zhengwen Wang ◽  
Qitao Xiao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Nucleic Acids ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Circular Rna ◽  
Circulating Tumor Dna ◽  
Clinical Applications ◽  
Biological Processes ◽  
Diagnosis And Therapy ◽  
Tumor Dna

Abstract Despite The Central Dogma states the destiny of gene as ‘DNA makes RNA and RNA makes protein’, the nucleic acids not only store and transmit genetic information but also, surprisingly, join in intracellular vital movement as a regulator of gene expression. Bioinformatics has contributed to knowledge for a series of emerging novel nucleic acids molecules. For typical cases, microRNA (miRNA), long noncoding RNA (lncRNA) and circular RNA (circRNA) exert crucial role in regulating vital biological processes, especially in malignant diseases. Due to extraordinarily heterogeneity among all malignancies, hepatocellular carcinoma (HCC) has emerged enormous limitation in diagnosis and therapy. Mechanistic, diagnostic and therapeutic nucleic acids for HCC emerging in past score years have been systematically reviewed. Particularly, we have organized recent advances on nucleic acids of HCC into three facets: (i) summarizing diverse nucleic acids and their modification (miRNA, lncRNA, circRNA, circulating tumor DNA and DNA methylation) acting as potential biomarkers in HCC diagnosis; (ii) concluding different patterns of three key noncoding RNAs (miRNA, lncRNA and circRNA) in gene regulation and (iii) outlining the progress of these novel nucleic acids for HCC diagnosis and therapy in clinical trials, and discuss their possibility for clinical applications. All in all, this review takes a detailed look at the advances of novel nucleic acids from potential of biomarkers and elaboration of mechanism to early clinical application in past 20 years.

scholarly journals Long Noncoding RNA LIFR-AS1: A New Player in Human Cancers

2022 ◽  
Vol 2022 ◽  
pp. 1-11
Author(s):  
Zhiqun Bai ◽  
Xuemei Wang ◽  
Zhen Zhang
Keyword(s):  
Leukemia Inhibitory Factor ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Clinicopathological Characteristics ◽  
Vital Role ◽  
Tumor Proliferation ◽  
Biological Processes ◽  
Leukemia Inhibitory Factor Receptor ◽  
Human Cancers

Emerging evidence has indicated that aberrantly expressed long noncoding RNAs (lncRNAs) play a vital role in various biological processes associated with tumorigenesis. Leukemia inhibitory factor receptor antisense RNA1 (LIFR-AS1) is a recently identified lncRNA transcribed in an antisense manner from the LIFR gene located on human chromosome 5p13.1. LIFR-AS1 regulates tumor proliferation, migration, invasion, apoptosis, and drug resistance through different mechanisms. Its expression level is related to the clinicopathological characteristics of tumors and plays a key role in tumor occurrence and development. In this review, we summarize the role of LIFR-AS1 in the development and progression of different cancers and highlight the potential for LIFR-AS1 to serve as a biomarker and therapeutic target for a variety of human cancers.

scholarly journals A Testis-Specific Long Noncoding RNA, Start, Is a Regulator of Steroidogenesis in Mouse Leydig Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Kai Otsuka ◽  
Shin Matsubara ◽  
Akira Shiraishi ◽  
Natsumi Takei ◽  
Yui Satoh ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Germ Cells ◽  
Noncoding Rna ◽  
Leydig Cells ◽  
Noncoding Rnas ◽  
Secondary Effect ◽  
Rna Seq ◽  
Qrt Pcr ◽  
Insight Into ◽  
Steroidogenic Genes

The testis expresses many long noncoding RNAs (lncRNAs), but their functions and overview of lncRNA variety are not well understood. The mouse Prss/Tessp locus contains six serine protease genes and two lncRNAs that have been suggested to play important roles in spermatogenesis. Here, we found a novel testis-specific lncRNA, Start (Steroidogenesis activating lncRNA in testis), in this locus. Start is 1822 nucleotides in length and was found to be localized mostly in the cytosol of germ cells and Leydig cells, although nuclear localization was also observed. Start-knockout (KO) mice generated by the CRISPR/Cas9 system were fertile and showed no morphological abnormality in adults. However, in adult Start-KO testes, RNA-seq and qRT-PCR analyses revealed an increase in the expression of steroidogenic genes such as Star and Hsd3b1, while ELISA analysis revealed that the testosterone levels in serum and testis were significantly low. Interestingly, at 8 days postpartum, both steroidogenic gene expression and testosterone level were decreased in Start-KO mice. Since overexpression of Start in two Leydig-derived cell lines resulted in elevation of the expression of steroidogenic genes including Star and Hsd3b1, Start is likely to be involved in their upregulation. The increase in expression of steroidogenic genes in adult Start-KO testes might be caused by a secondary effect via the androgen receptor autocrine pathway or the hypothalamus-pituitary-gonadal axis. Additionally, we observed a reduced number of Leydig cells at 8 days postpartum. Collectively, our results strongly suggest that Start is a regulator of steroidogenesis in Leydig cells. The current study provides an insight into the overall picture of the function of testis lncRNAs.

Noncoding Rnas Emerging as Novel Biomarkers in Pancreatic Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4601-4604 ◽  
Author(s):  
Ingrid Garajová ◽  
Rita Balsano ◽  
Chiara Tommasi ◽  
Elisa Giovannetti
Keyword(s):  
Pancreatic Cancer ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Predictive Biomarkers ◽  
Chemotherapy Response ◽  
Biological Processes ◽  
Metastatic Behavior ◽  
Novel Biomarkers ◽  
Non Coding Rnas

Noncoding RNAs play important regulatory roles in diverse biological processes and their misregulation might lead to different diseases, including cancer. Previous studies have reported the evolving role of miRNAs as new potential biomarkers in cancer diagnosis, prognosis, as well as predictive biomarkers of chemotherapy response or therapeutic targets. In this review, we outline the involvement of noncoding RNA in pancreatic cancer, providing an overview of known miRNAs in its diagnosis, prognosis and chemoresistance. In addition, we discuss the influence of non-coding RNAs in the metastatic behavior of pancreatic cancer, as well as the role of diet in epigenetic regulation of non-coding RNAs in cancer, which can, in turn, lead the development of new prevention’s techniques or novel targets for cancer therapy.

scholarly journals Differential long noncoding RNA profiling of BMI in twins

Epigenomics ◽  
2020 ◽  
Vol 12 (17) ◽  
pp. 1531-1541
Author(s):  
Weilong Li ◽  
Jan Baumbach ◽  
Martin J Larsen ◽  
Afsaneh Mohammadnejad ◽  
Jesper Lund ◽  
...  
Keyword(s):  
Whole Blood ◽  
Generalized Estimating Equations ◽  
Noncoding Rna ◽  
Kidney Development ◽  
Noncoding Rnas ◽  
Monozygotic Twin ◽  
Causal Effects ◽  
Biological Processes ◽  
Rna Profiling ◽  
False Discovery

Aim: Many efforts have been deployed to identify genetic variants associated with BMI. Alternatively, we explore epigenetic contribution to BMI variation by focusing on long noncoding RNAs (lncRNAs) which represents a key layer of epigenetic control. Materials & methods: We analyzed lncRNA expression in whole blood of 229 monozygotic twin pairs in association with BMI using generalized estimating equations. Results & conclusion: Six lncRNA probes were identified as significant (false discovery rate <0.05), with BMI showing causal effects on the expression of the significant lncRNAs. Functional annotation of differential profiles identified Gene ontology biological processes including kidney development, regulations of lipid biosynthetic process, circadian rhythm, notch signaling, etc. Whole blood lncRNAs are significantly expressed in response to BMI variation.

scholarly journals LINC00261: a burgeoning long noncoding RNA related to cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Menggang Zhang ◽  
Fang Gao ◽  
Xiao Yu ◽  
Qiyao Zhang ◽  
Zongzong Sun ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Cancer Colorectal ◽  
Tumor Development ◽  
Noncoding Rnas ◽  
Biological Processes ◽  
Biological Mechanisms ◽  
Protein Coding ◽  
Cellular Processes

AbstractLong noncoding RNAs (lncRNAs), are transcripts longer than 200 nucleotides that are considered to be vital regulators of many cellular processes, particularly in tumorigenesis and cancer progression. long intergenic non-protein coding RNA 261 (LINC00261), a recently discovered lncRNA, is abnormally expressed in a variety of human malignancies, including pancreatic cancer, gastric cancer, colorectal cancer, lung cancer, hepatocellular carcinoma, breast cancer, laryngeal carcinoma, endometrial carcinoma, esophageal cancer, prostate cancer, choriocarcinoma, and cholangiocarcinoma. LINC00261 mainly functions as a tumor suppressor that regulates a variety of biological processes in the above-mentioned cancers, such as cell proliferation, apoptosis, motility, chemoresistance, and tumorigenesis. In addition, the up-regulation of LINC00261 is closely correlated with both favorable prognoses and many clinical characteristics. In the present review, we summarize recent research documenting the expression and biological mechanisms of LINC00261 in tumor development. These findings suggest that LINC00261, as a tumor suppressor, has bright prospects both as a biomarker and a therapeutic target.

scholarly journals Tumor-derived exosomal long noncoding RNA LINC01133, regulated by Periostin, contributes to pancreatic ductal adenocarcinoma epithelial-mesenchymal transition through the Wnt/β-catenin pathway by silencing AXIN2

Oncogene ◽  
2021 ◽  
Vol 40 (17) ◽  
pp. 3164-3179
Author(s):  
Yang Liu ◽  
Tianchi Tang ◽  
Xiaosheng Yang ◽  
Peng Qin ◽  
Pusen Wang ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Noncoding Rna ◽  
Pancreatic Tumor ◽  
Epithelial Mesenchymal Transition ◽  
Noncoding Rnas ◽  
Ductal Adenocarcinoma ◽  
Overall Survival Rate ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells

AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies and rapidly progressive diseases. Exosomes and long noncoding RNAs (lncRNAs) are emerging as vital mediators in tumor cells and their microenvironment. However, the detailed roles and mechanisms of exosomal lncRNAs in PDAC progression remain unknown. Here, we aimed to clarify the clinical significance and mechanisms of exosomal lncRNA 01133 (LINC01133) in PDAC. We analyzed the expression of LINC01133 in PDAC and found that exosomal LINC01133 expression was high and positively correlated with higher TNM stage and poor overall survival rate of PDAC patients. Further research demonstrated that Periostin could increase exosome secretion and then enhance LINC01133 expression. In addition, Periostin increased p-EGFR, p-Erk, and c-myc expression, and c-myc could bind to the LINC01133 promoter region. These findings suggested that LINC01133 can be regulated by Periostin via EGFR pathway activity. We also observed that LINC01133 promoted the proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) of pancreatic cancer cells. We subsequently evaluated the effect of LINC01133 on the Wnt/β-catenin pathway and confirmed that LINC01133 can interact with Enhancer Of Zeste Homolog 2 (EZH2) and then promote H3K27 trimethylation. This can further silence AXIN2 and suppress GSK3 activity, ultimately activating β-catenin. Collectively, these data indicate that exosomal LINC01133 plays an important role in pancreatic tumor progression, and targeting LINC01133 may provide a potential treatment strategy for PDAC.

scholarly journals Equine Genital Squamous Cell Carcinoma Associated with EcPV2 Infection: RANKL Pathway Correlated to Inflammation and Wnt Signaling Activation

Biology ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 244
Author(s):  
Samanta Mecocci ◽  
Ilaria Porcellato ◽  
Federico Armando ◽  
Luca Mechelli ◽  
Chiara Brachelente ◽  
...  
Keyword(s):  
Gene Expression ◽  
Wnt Signaling ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Animal Health ◽  
Wnt Signaling Pathway ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Signaling Activation ◽  
Expression Evaluation

Equine genital squamous cell carcinomas (egSCCs) are among the most common equine tumors after sarcoids, severely impairing animal health and welfare. Equus caballus papillomavirus type 2 (EcPV2) infection is often related to these tumors. The aim of this study was to clarify the molecular mechanisms behind egSCCs associated with EcPV2 infection, investigating receptor activator of nuclear factor-kappa B ligand (RANKL) signaling in NF-kB pathway, together with the Wnt and IL17 signaling pathways. We analyzed the innate immune response through gene expression evaluation of key cytokines and transcription factors. Moreover, Ki67 index was assessed with immunohistochemistry. EcPV2-E6 DNA was checked, and viral presence was confirmed in 21 positive out to 23 cases (91%). Oncogene expression was confirmed in 14 cases (60.8%) for E6 and in 8 (34.7%) for E2. RANKL, nuclear factor kappa-light-chain-enhancer of activated B cells (NFKB)-p50, NFKBp65, interleukin (IL)-6, IL17, IL23p19, IL8, IL12p35, IL12p40, β-catenin (BCATN1), FOS like 1 (FOSL1), and lymphoid enhancer binding factor 1 (LEF1) showed a significant upregulation in tumor samples compared to healthy tissues. Our results describe an inflammatory environment characterized by the activation of RANKL/RANK and IL17 with the relative downstream pathways, and a positive modulation of inflammatory cytokines genes such as IL6 and IL8. Moreover, the increase of BCATN1, FOSL1, and LEF1 gene expression suggests an activation of both canonical and non-canonical Wnt signaling pathway that could be critical for carcinogenesis and tumor progression.

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