scholarly journals Deciphering the Mounting Complexity of the p53 Regulatory Network in Correlation to Long Non-Coding RNAs (lncRNAs) in Ovarian Cancer

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 527 ◽  
Author(s):  
Sonali Pal ◽  
Manoj Garg ◽  
Amit Kumar Pandey
Keyword(s):  
Ovarian Cancer ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Critical Role ◽  
Functional Characterization ◽  
Great Promise ◽  
Altered Expression ◽  
Disease Biology ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation

Amongst the various gynecological malignancies affecting female health globally, ovarian cancer is one of the predominant and lethal among all. The identification and functional characterization of long non-coding RNAs (lncRNAs) are made possible with the advent of RNA-seq and the advancement of computational logarithm in understanding human disease biology. LncRNAs can interact with deoxyribonucleic acid (DNA), ribonucleic acid (RNA), proteins and their combinations. Moreover, lncRNAs regulate orchestra of diverse functions including chromatin organization and transcriptional and post-transcriptional regulation. LncRNAs have conferred their critical role in key biological processes in human cancer including tumor initiation, proliferation, cell cycle, apoptosis, necroptosis, autophagy, and metastasis. The interwoven function of tumor-suppressor protein p53-linked lncRNAs in the ovarian cancer paradigm is of paramount importance. Several lncRNAs operate as p53 regulators or effectors and modulates a diverse array of functions either by participating in various signaling cascades or via interaction with different proteins. This review highlights the recent progress made in the identification of p53 associated lncRNAs while elucidating their molecular mechanisms behind the altered expression in ovarian cancer tumorigenesis. Moreover, the development of novel clinical and therapeutic strategies for targeting lncRNAs in human cancers harbors great promise.

ADAMTS9-AS2: A functional long non-coding RNA in tumorigenesis

2021 ◽  
Vol 27 ◽  
Author(s):  
Wen Xu ◽  
Bei Wang ◽  
Yuxuan Cai ◽  
Jinlan Chen ◽  
Xing Lv ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Signaling Pathways ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Migration Inhibition ◽  
Cancer Proliferation ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

Background: Long non-coding RNAs (lncRNA) have been identified as novel molecular regulators in cancers. LncRNA ADAMTS9-AS2 can mediate the occurrence and development of cancer through various ways such as regulating miRNAs, activating the classical signaling pathways in cancer, and so on, which have been studied by many scholars. In this review, we summarize the molecular mechanisms of ADAMTS9-AS2 in different human cancers. Methods: Through a systematic search of PubMed, lncRNA ADAMTS9-AS2 mediated molecular mechanisms in cancer are summarized inductively. Results: ADAMTS9-AS2 aberrantly expression in different cancers is closely related to cancer proliferation, invasion, migration, inhibition of apoptosis. The involvement of ADAMTS9-AS2 in DNA methylation, mediating PI3K / Akt / mTOR signaling pathways, regulating miRNAs and proteins, and such shows its significant potential as a therapeutic cancer target. Conclusion: LncRNA ADAMTS9-AS2 can become a promising biomolecular marker and a therapeutic target for human cancer.

scholarly journals Genome-Based Identification of Cancer Genes by Proviral Tagging in Mouse Retrovirus-Induced T-Cell Lymphomas

2003 ◽  
Vol 77 (3) ◽  
pp. 2056-2062 ◽  
Author(s):  
Rachel Kim ◽  
Alla Trubetskoy ◽  
Takeshi Suzuki ◽  
Nancy A. Jenkins ◽  
Neal G. Copeland ◽  
...  
Keyword(s):  
T Cell ◽  
Molecular Mechanisms ◽  
Mouse Genome ◽  
Human Cancer ◽  
Inverse Pcr ◽  
Ras Signaling ◽  
Cancer Genes ◽  
Altered Expression ◽  
New Genes ◽  
T Cell Lymphomas

ABSTRACT The identification of tumor-inducing genes is a driving force for elucidating the molecular mechanisms underlying cancer. Many retroviruses induce tumors by insertion of viral DNA adjacent to cellular oncogenes, resulting in altered expression and/or structure of the encoded proteins. The availability of the mouse genome sequence now allows analysis of retroviral common integration sites in murine tumors to be used as a genetic screen for identification of large numbers of candidate cancer genes. By positioning the sequences of inverse PCR-amplified, virus-host junction fragments within the mouse genome, 19 target genes were identified in T-cell lymphomas induced by the retrovirus SL3-3. The candidate cancer genes included transcription factors (Fos, Gfi1, Lef1, Myb, Myc, Runx3, and Sox3), all three D cyclins, Ras signaling pathway components (Rras2/TC21 and Rasgrp1), and Cmkbr7/CCR7. The most frequent target was Rras2. Insertions as far as 57 kb away from the transcribed portion were associated with substantially increased transcription of Rras2, and no coding sequence mutations, including those typically involved in Ras activation, were detected. These studies demonstrate the power of genome-based analysis of retroviral insertion sites for cancer gene discovery, identify several new genes worth examining for a role in human cancer, and implicate the pathways in which those genes act in lymphomagenesis. They also provide strong genetic evidence that overexpression of unmutated Rras2 contributes to tumorigenesis, thus suggesting that it may also do so if it is inappropriately expressed in human tumors.

scholarly journals Long non-coding RNAs in plants: emerging modulators of gene activity in development and stress responses

Planta ◽  
2020 ◽  
Vol 252 (5) ◽  
Author(s):  
Li Chen ◽  
Qian-Hao Zhu ◽  
Kerstin Kaufmann
Keyword(s):  
Stress Responses ◽  
Translational Regulation ◽  
Molecular Mechanisms ◽  
Functional Characterization ◽  
Reproductive Organs ◽  
Gene Activity ◽  
Protein Coding ◽  
Wide Range ◽  
Non Coding Rnas ◽  
Coding Potential

Abstract Main conclusion Long non-coding RNAs modulate gene activity in plant development and stress responses by various molecular mechanisms. Abstract Long non-coding RNAs (lncRNAs) are transcripts larger than 200 nucleotides without protein coding potential. Computational approaches have identified numerous lncRNAs in different plant species. Research in the past decade has unveiled that plant lncRNAs participate in a wide range of biological processes, including regulation of flowering time and morphogenesis of reproductive organs, as well as abiotic and biotic stress responses. LncRNAs execute their functions by interacting with DNA, RNA and protein molecules, and by modulating the expression level of their targets through epigenetic, transcriptional, post-transcriptional or translational regulation. In this review, we summarize characteristics of plant lncRNAs, discuss recent progress on understanding of lncRNA functions, and propose an experimental framework for functional characterization.

scholarly journals Proteomics Reveals the Changes that Contribute to Fusarium Head Blight Resistance in Wheat

2020 ◽  
pp. PHYTO-05-20-017
Author(s):  
Mingming Yang ◽  
Xianguo Wang ◽  
Jian Dong ◽  
Wanchun Zhao ◽  
Tariq Alam ◽  
...  
Keyword(s):  
Fusarium Head Blight ◽  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Functional Characterization ◽  
Fusarium Head Blight Resistance ◽  
Defense Responses ◽  
Head Blight ◽  
Resistance Response ◽  
Fhb Resistance

Fusarium head blight (FHB) is a devastating disease of wheat, causing yield losses and quality reduction as a result of mycotoxin production. In this study, iTRAQ (isobaric tags for relative and absolute quantification)- labeling-based mass spectrometry was employed to characterize the proteome in wheat cultivars Xinong 538 and Zhoumai 18 with contrasting levels of FHB resistance as a means to elucidate the molecular mechanisms contributing to FHB resistance. A total of 13,669 proteins were identified in the two cultivars 48 h after Fusarium graminearum inoculation. Among these, 2,505 unique proteins exclusively accumulated in Xinong 538 (resistant) and 887 proteins in Zhoumai 18 (susceptible). Gene Ontology enrichment analysis showed that most differentially accumulated proteins (DAPs) from both cultivars were assigned to the following categories: metabolic process, single-organism process, cellular process, and response to stimulus. Kyoto Encyclopedia of Genes and Genomes analysis showed that a greater number of proteins belonging to different metabolic pathways were identified in Xinong 538 compared with Zhoumai 18. Specifically, DAPs from the FHB-resistant cultivar Xinong 538 populated categories of metabolic pathways related to plant–pathogen interaction. These DAPs might play a critical role in defense responses exhibited by Xinong 538. DAPs from both genotypes were assigned to all wheat chromosomes except chromosome 6B, with approximately 30% mapping to wheat chromosomes 2B, 3B, 5B, and 5D. Twenty single nucleotide polymorphism markers, flanking DAPs on chromosomes 1B, 3B, 5B, and 6A, overlapped with the location of earlier mapped FHB-resistance quantitative trait loci. The data provide evidence for the involvement of several DAPs in the early stages of the FHB-resistance response in wheat; however, further functional characterization of candidate proteins is warranted.

scholarly journals Emerging Role of Long Non-Coding RNAs in Diabetic Vascular Complications

2021 ◽  
Vol 12 ◽  
Author(s):  
Vinay Singh Tanwar ◽  
Marpadga A. Reddy ◽  
Rama Natarajan
Keyword(s):  
Drug Targets ◽  
Molecular Mechanisms ◽  
Microvascular Complications ◽  
Vascular Complications ◽  
Protein Coding ◽  
Altered Expression ◽  
Diabetic Vascular Complications ◽  
Obesity And Diabetes ◽  
Non Coding Rnas ◽  
Species Specific

Chronic metabolic disorders such as obesity and diabetes are associated with accelerated rates of macrovascular and microvascular complications, which are leading causes of morbidity and mortality worldwide. Further understanding of the underlying molecular mechanisms can aid in the development of novel drug targets and therapies to manage these disorders more effectively. Long non-coding RNAs (lncRNAs) that do not have protein-coding potential are expressed in a tissue- and species-specific manner and regulate diverse biological processes. LncRNAs regulate gene expression in cis or in trans through various mechanisms, including interaction with chromatin-modifying proteins and other regulatory proteins and via posttranscriptional mechanisms, including acting as microRNA sponges or as host genes of microRNAs. Emerging evidence suggests that major pathological factors associated with diabetes such as high glucose, free fatty acids, proinflammatory cytokines, and growth factors can dysregulate lncRNAs in inflammatory, cardiac, vascular, and renal cells leading to altered expression of key inflammatory genes and fibrotic genes associated with diabetic vascular complications. Here we review recent reports on lncRNA characterization, functions, and mechanisms of action in diabetic vascular complications and translational approaches to target them. These advances can provide new insights into the lncRNA-dependent actions and mechanisms underlying diabetic vascular complications and uncover novel lncRNA-based biomarkers and therapies to reduce disease burden and mortality.

scholarly journals Recent Advances in the Pathogenesis and Treatment of Chronic Lymphocytic Leukemia

PRILOZI ◽  
2014 ◽  
Vol 35 (3) ◽  
pp. 105-120
Author(s):  
Dimitar G. Efremov ◽  
Luca Laurenti
Keyword(s):  
Molecular Mechanisms ◽  
Critical Role ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Great Promise ◽  
Next Generation Sequencing Technology ◽  
Recent Advances ◽  
Leukaemic Cells ◽  
Near Future

AbstractChronic lymphocytic leukaemia (CLL) is a common lymphoid malignancy characterized by the expansion and progressive accumulation of mature autoreactive B lymphocytes. The disease is clinically heterogeneous and incurable by standard chemotherapy. A major feature of the disease is the marked dependence of the leukaemic cells on various microenvironmental stimuli, which promote leukaemia cell growth, survival, and drug-resistance. Recently, considerable progress has been made in the understanding of the molecular mechanisms that drive CLL. The identification of recurrent genetic lesions using next generation sequencing technology has provided new data on the pathophysiology of the disease and has improved its prognostication. The recognition of the critical role of the B cell receptor (BCR) in driving the disease has resulted in the development of BCR pathway inhibitors that have the potential to completely transform CLL treatment in the near future. Other novel therapeutic agents, such as BCL2 antagonists and chimeric antigen receptor (CAR)-modified T-cells, are also showing great promise in clinical trials. In this review, we summarize some of these recent advances, with a particular focus on the BCR and corresponding pathway inhibitors.

scholarly journals Long Non-Coding RNA Expression Profiling in Aging Rats with Erectile Dysfunction

2015 ◽  
Vol 37 (4) ◽  
pp. 1513-1526 ◽  
Author(s):  
Lianjun Pan ◽  
Jiehua Ma ◽  
Feng Pan ◽  
Dan Zhao ◽  
Jianping Gao
Keyword(s):  
Erectile Dysfunction ◽  
Expression Profiles ◽  
Critical Role ◽  
Altered Expression ◽  
Aged People ◽  
Age Related ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Rna Expression Profiling ◽  
Long Non Coding Rna

Background/Aims: Erectile dysfunction (ED) in aged people remains a topic of interest to andrological physicians. Long non-coding RNAs (lncRNAs), which form the largest group of non-coding RNAs, have been shown to regulate various biological processes. The function of lncRNAs in age-related erectile dysfunction (A-ED) pathogenesis remains poorly understood. Methods: This study aims to assess the differential expression profiles of mRNAs and lncRNAs between A-ED and normal control (NC) samples. Using a second-generation lncRNA microarray, we detected a total of 8,744 lncRNAs and 13,585 coding transcripts. Results: We identified 608 up-regulated and 406 down-regulated lncRNAs in A-ED compared with NC samples, by setting a filter of fold-change >2.0. Gene Ontology and pathway analysis revealed that a muscle contraction disorder induced by abnormal ion channels might play a critical role in the pathogenesis of A-ED. Conclusion: Our results show significantly altered expression profiles of lncRNAs and mRNAs between A-ED and NC. This study may provide information for further research on A-ED and may be helpful for finding a new therapeutic target for A-ED.

scholarly journals Long Non-Coding RNAs: the New Horizon of Gene Regulation in Ovarian Cancer

2017 ◽  
Vol 44 (3) ◽  
pp. 948-966 ◽  
Author(s):  
Tesfaye Worku ◽  
Dinesh Bhattarai ◽  
Duncan Ayers ◽  
Kai Wang ◽  
Chen Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Gene Regulation ◽  
Molecular Mechanisms ◽  
Future Directions ◽  
Diagnostic Biomarkers ◽  
Functional Roles ◽  
Gene Therapies ◽  
Wide Range ◽  
Recent Developments ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs), a class of non-coding transcripts, have recently been emerging with heterogeneous molecular actions, adding a new layer of complexity to gene-regulation networks in tumorigenesis. LncRNAs are considered important factors in several ovarian cancer histotypes, although few have been identified and characterized. Owing to their complexity and the lack of adapted molecular technology, the roles of most lncRNAs remain mysterious. Some lncRNAs have been reported to play functional roles in ovarian cancer and can be used as classifiers for personalized medicine. The intrinsic features of lncRNAs govern their various molecular mechanisms and provide a wide range of platforms to design different therapeutic strategies for treating cancer at a particular stage. Although we are only beginning to understand the functions of lncRNAs and their interactions with microRNAs (miRNAs) and proteins, the expanding literature indicates that lncRNA-miRNA interactions could be useful biomarkers and therapeutic targets for ovarian cancer. In this review, we discuss the genetic variants of lncRNAs, heterogeneous mechanisms of actions of lncRNAs in ovarian cancer tumorigenesis, and drug resistance. We also highlight the recent developments in using lncRNAs as potential prognostic and diagnostic biomarkers. Lastly, we discuss potential approaches for linking lncRNAs to future gene therapies, and highlight future directions in the field of ovarian cancer research.

scholarly journals Etiology and Pathogenesis of Epithelial Ovarian Cancer

2007 ◽  
Vol 23 (5-6) ◽  
pp. 367-376 ◽  
Author(s):  
Samuel C. Mok ◽  
Joseph Kwong ◽  
William R. Welch ◽  
Goli Samimi ◽  
Laurent Ozbun ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Molecular Mechanisms ◽  
Complex Disease ◽  
Critical Role ◽  
Epidemiological Studies ◽  
Genetic Studies ◽  
Genetic Changes ◽  
Disease Phenotypes ◽  
Stromal Microenvironment ◽  
Insight Into

Ovarian cancer is complex disease composed of different histological grades and types. However, the underlying molecular mechanisms involved in the development of different phenotypes remain largely unknown. Epidemiological studies identified multiple exogenous and endogenous risk factors for ovarian cancer development. Among them, an inflammatory stromal microenvironment seems to play a critical role in the initiation of the disease. The interaction between such a microenvironment, genetic polymorphisms, and different epithelial components such as endosalpingiosis, endometriosis, and ovarian inclusion cyst in the ovarian cortex may induce different genetic changes identified in the epithelial component of different histological types of ovarian tumors. Genetic studies on different histological grades and types provide insight into the pathogenetic pathways for the development of different disease phenotypes. However, the link between all these genetic changes and the etiological factors remains to be established.

scholarly journals Breast Cancer and the Other Non-Coding RNAs

2021 ◽  
Vol 22 (6) ◽  
pp. 3280
Author(s):  
Dana Dvorská ◽  
Dušan Braný ◽  
Marcela Ňachajová ◽  
Erika Halašová ◽  
Zuzana Danková
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Breast Cancer Cell Lines ◽  
Altered Expression ◽  
Factors Affecting ◽  
Mesenchymal Transition ◽  
Non Coding Rnas ◽  
Endothelial To Mesenchymal Transition ◽  
Molecular Therapeutic

Breast cancer is very heterogenous and the most common gynaecological cancer, with various factors affecting its development. While its impact on human lives and national health budgets is still rising in almost all global areas, many molecular mechanisms affecting its onset and development remain unclear. Conventional treatments still prove inadequate in some aspects, and appropriate molecular therapeutic targets are required for improved outcomes. Recent scientific interest has therefore focused on the non-coding RNAs roles in tumour development and their potential as therapeutic targets. These RNAs comprise the majority of the human transcript and their broad action mechanisms range from gene silencing to chromatin remodelling. Many non-coding RNAs also have altered expression in breast cancer cell lines and tissues, and this is often connected with increased proliferation, a degraded extracellular environment, and higher endothelial to mesenchymal transition. Herein, we summarise the known abnormalities in the function and expression of long non-coding RNAs, Piwi interacting RNAs, small nucleolar RNAs and small nuclear RNAs in breast cancer, and how these abnormalities affect the development of this deadly disease. Finally, the use of RNA interference to suppress breast cancer growth is summarised.

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