scholarly journals Dysregulated Expression of Long Noncoding RNAs in Ovarian Cancer

2016 ◽  
Vol 26 (9) ◽  
pp. 1564-1570 ◽  
Author(s):  
Yancheng Zhong ◽  
Dan Gao ◽  
Shiwei He ◽  
Cijun Shuai ◽  
Shuping Peng

AbstractOvarian cancer is the leading cause of death among women with gynecologic malignancies. The development and progression of ovarian cancer are complex and a multiple-step process. New biomarker molecules for diagnostic and prognostic are essential for novel therapeutic targets and to extend the survival time of patients with ovarian cancer. Long noncoding RNAs (lncRNAs) are non–protein-coding transcripts longer than 200 nucleotides that have recently been found as key regulators of various biological processes and to be involved in the development and progression of many diseases including cancers. In this review, we summarized the expression pattern of several dysregulated lncRNAs (HOTAIR, H19, XIST, and HOST2) and the functional molecular mechanism of these lncRNAs on the initiation and progression of ovarian cancer. The lncRNAs as biomarkers may be used for current and future clinical diagnosis, therapeutics, and prognosis.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hidenori Tani ◽  
Ayaka Numajiri ◽  
Motohide Aoki ◽  
Tomonari Umemura ◽  
Tetsuya Nakazato

AbstractLong noncoding RNAs (lncRNAs) are non-protein-coding transcripts >200 nucleotides in length that have been shown to play important roles in various biological processes. The mechanisms underlying the induction of lncRNA expression by chemical exposure remain to be determined. We identified a novel class of short-lived lncRNAs with half-lives (t1/2) ≤4 hours in human HeLa Tet-off cells, which have been suggested to express many lncRNAs with regulatory functions. As they may affect various human biological processes, short-lived lncRNAs may be useful indicators of the degree of stress on chemical exposure. In the present study, we identified four short-lived lncRNAs, designated as OIP5-AS1, FLJ46906, LINC01137, and GABPB1-AS1, which showed significantly upregulated expression following exposure to hydrogen peroxide (oxidative stress), mercury II chloride (heavy metal stress), and etoposide (DNA damage stress) in human HepG2 cells. These lncRNAs may be useful indicators of chemical stress responses. The levels of these lncRNAs in the cells were increased because of chemical stress-induced prolongation of their decay. These lncRNAs were degraded by nuclear RNases, which are components of the exosome and XRN2, and chemical exposure inhibited the RNase activities within the cells.


2017 ◽  
Vol 2017 ◽  
pp. 1-13
Author(s):  
Fuquan Chen ◽  
Jiaojiao Ji ◽  
Jian Shen ◽  
Xinyi Lu

Most of the human genome can be transcribed into RNAs, but only a minority of these regions produce protein-coding mRNAs whereas the remaining regions are transcribed into noncoding RNAs. Long noncoding RNAs (lncRNAs) were known for their influential regulatory roles in multiple biological processes such as imprinting, dosage compensation, transcriptional regulation, and splicing. The physiological functions of protein-coding genes have been extensively characterized through genome editing in pluripotent stem cells (PSCs) in the past 30 years; however, the study of lncRNAs with genome editing technologies only came into attentions in recent years. Here, we summarize recent advancements in dissecting the roles of lncRNAs with genome editing technologies in PSCs and highlight potential genome editing tools useful for examining the functions of lncRNAs in PSCs.


2021 ◽  
Vol 22 (8) ◽  
pp. 4072
Author(s):  
Tushar Singh Barwal ◽  
Uttam Sharma ◽  
Sonali Bazala ◽  
Ipsa Singh ◽  
Manju Jain ◽  
...  

Aromatase inhibitors (AIs) such as anastrozole, letrozole, and exemestane have shown to prevent metastasis and angiogenesis in estrogen receptor (ER)-positive breast and ovarian tumors. They function primarily by reducing estrogen production in ER-positive post-menopausal breast and ovarian cancer patients. Unfortunately, current AI-based therapies often have detrimental side-effects, along with acquired resistance, with increased cancer recurrence. Thus, there is an urgent need to identify novel AIs with fewer side effects and improved therapeutic efficacies. In this regard, we and others have recently suggested noncoding RNAs (ncRNAs), specifically microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), as potential molecular targets for utilization in modulating cancer hallmarks and overcoming drug resistance in several cancers, including ER-positive breast and ovarian cancer. Herein, we describe the disruptive functions of several miRNAs and lncRNAs seen in dysregulated cancer metabolism, with a focus on the gene encoding for aromatase (CYP19A1 gene) and estrogen synthesis as a novel therapeutic approach for treating ER-positive breast and ovarian cancers. Furthermore, we discuss the oncogenic and tumor-suppressive roles of several miRNAs (oncogenic miRNAs: MIR125b, MIR155, MIR221/222, MIR128, MIR2052HG, and MIR224; tumor-suppressive miRNAs: Lethal-7f, MIR27B, MIR378, and MIR98) and an oncogenic lncRNA (MIR2052HG) in aromatase-dependent cancers via transcriptional regulation of the CYP19A1 gene. Additionally, we discuss the potential effects of dysregulated miRNAs and lncRNAs on the regulation of critical oncogenic molecules, such as signal transducer, and activator of transcription 3, β-catenin, and integrins. The overall goal of this review is to stimulate further research in this area and to facilitate the development of ncRNA-based approaches for more efficacious treatments of ER-positive breast and ovarian cancer patients, with a slight emphasis on associated treatment–delivery mechanisms.


2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Yun Xiao ◽  
Yanling Lv ◽  
Hongying Zhao ◽  
Yonghui Gong ◽  
Jing Hu ◽  
...  

Long noncoding RNAs (lncRNAs) have been shown to play key roles in various biological processes. However, functions of most lncRNAs are poorly characterized. Here, we represent a framework to predict functions of lncRNAs through construction of a regulatory network between lncRNAs and protein-coding genes. Using RNA-seq data, the transcript profiles of lncRNAs and protein-coding genes are constructed. Using the Bayesian network method, a regulatory network, which implies dependency relations between lncRNAs and protein-coding genes, was built. In combining protein interaction network, highly connected coding genes linked by a given lncRNA were subsequently used to predict functions of the lncRNA through functional enrichment. Application of our method to prostate RNA-seq data showed that 762 lncRNAs in the constructed regulatory network were assigned functions. We found that lncRNAs are involved in diverse biological processes, such as tissue development or embryo development (e.g., nervous system development and mesoderm development). By comparison with functions inferred using the neighboring gene-based method and functions determined using lncRNA knockdown experiments, our method can provide comparable predicted functions of lncRNAs. Overall, our method can be applied to emerging RNA-seq data, which will help researchers identify complex relations between lncRNAs and coding genes and reveal important functions of lncRNAs.


2021 ◽  
Vol 72 (1) ◽  
Author(s):  
Andrzej T. Wierzbicki ◽  
Todd Blevins ◽  
Szymon Swiezewski

Plants have an extraordinary diversity of transcription machineries, including five nuclear DNA-dependent RNA polymerases. Four of these enzymes are dedicated to the production of long noncoding RNAs (lncRNAs), which are ribonucleic acids with functions independent of their protein-coding potential. lncRNAs display a broad range of lengths and structures, but they are distinct from the small RNA guides of RNA interference (RNAi) pathways. lncRNAs frequently serve as structural, catalytic, or regulatory molecules for gene expression. They can affect all elements of genes, including promoters, untranslated regions, exons, introns, and terminators, controlling gene expression at various levels, including modifying chromatin accessibility, transcription, splicing, and translation. Certain lncRNAs protect genome integrity, while others respond to environmental cues like temperature, drought, nutrients, and pathogens. In this review, we explain the challenge of defining lncRNAs, introduce the machineries responsible for their production, and organize this knowledge by viewing the functions of lncRNAs throughout the structure of a typical plant gene. Expected final online publication date for the Annual Review of Plant Biology, Volume 72 is May 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


2020 ◽  
Vol 6 (2) ◽  
pp. 24 ◽  
Author(s):  
Liming Chen ◽  
Yifan Bao ◽  
Suzhen Jiang ◽  
Xiao-bo Zhong

Long noncoding RNAs (lncRNAs) are RNAs with a length of over 200 nucleotides that do not have protein-coding abilities. Recent studies suggest that lncRNAs are highly involved in physiological functions and diseases. lncRNAs HNF1α-AS1 and HNF4α-AS1 are transcripts of lncRNA genes HNF1α-AS1 and HNF4α-AS1, which are antisense lncRNA genes located in the neighborhood regions of the transcription factor (TF) genes HNF1α and HNF4α, respectively. HNF1α-AS1 and HNF4α-AS1 have been reported to be involved in several important functions in human physiological activities and diseases. In the liver, HNF1α-AS1 and HNF4α-AS1 regulate the expression and function of several drug-metabolizing cytochrome P450 (P450) enzymes, which also further impact P450-mediated drug metabolism and drug toxicity. In addition, HNF1α-AS1 and HNF4α-AS1 also play important roles in the tumorigenesis, progression, invasion, and treatment outcome of several cancers. Through interacting with different molecules, including miRNAs and proteins, HNF1α-AS1 and HNF4α-AS1 can regulate their target genes in several different mechanisms including miRNA sponge, decoy, or scaffold. The purpose of the current review is to summarize the identified functions and mechanisms of HNF1α-AS1 and HNF4α-AS1 and to discuss the future directions of research of these two lncRNAs.


2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Ling Wei ◽  
Xingwu Wang ◽  
Liyan Lv ◽  
Jibing Liu ◽  
Huaixin Xing ◽  
...  

Abstract Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the second most lethal human cancer. A portion of patients with advanced HCC can significantly benefit from treatments with sorafenib, adriamycin, 5-fluorouracil and platinum drugs. However, most HCC patients eventually develop drug resistance, resulting in a poor prognosis. The mechanisms involved in HCC drug resistance are complex and inconclusive. Human transcripts without protein-coding potential are known as noncoding RNAs (ncRNAs), including microRNAs (miRNAs), small nucleolar RNAs (snoRNAs), long noncoding RNAs (lncRNAs) and circular RNA (circRNA). Accumulated evidences demonstrate that several deregulated miRNAs and lncRNAs are important regulators in the development of HCC drug resistance which elucidates their potential clinical implications. In this review, we summarized the detailed mechanisms by which miRNAs and lncRNAs affect HCC drug resistance. Multiple tumor-specific miRNAs and lncRNAs may serve as novel therapeutic targets and prognostic biomarkers for HCC.


Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2701
Author(s):  
Naiade Calanca ◽  
Cecilie Abildgaard ◽  
Cláudia Aparecida Rainho ◽  
Silvia Regina Rogatto

Comprehensive large-scale sequencing and bioinformatics analyses have uncovered a myriad of cancer-associated long noncoding RNAs (lncRNAs). Aberrant expression of lncRNAs is associated with epigenetic reprogramming during tumor development and progression, mainly due to their ability to interact with DNA, RNA, or proteins to regulate gene expression. LncRNAs participate in the control of gene expression patterns during development and cell differentiation and can be cell and cancer type specific. In this review, we described the potential of lncRNAs for clinical applications in ovarian cancer (OC). OC is a complex and heterogeneous disease characterized by relapse, chemoresistance, and high mortality rates. Despite advances in diagnosis and treatment, no significant improvements in long-term survival were observed in OC patients. A set of lncRNAs was associated with survival and response to therapy in this malignancy. We manually curated databases and used bioinformatics tools to identify lncRNAs implicated in the epigenetic regulation, along with examples of direct interactions between the lncRNAs and proteins of the epigenetic machinery in OC. The resources and mechanisms presented herein can improve the understanding of OC biology and provide the basis for further investigations regarding the selection of novel biomarkers and therapeutic targets.


Medicine ◽  
2018 ◽  
Vol 97 (32) ◽  
pp. e11481 ◽  
Author(s):  
Li Ning ◽  
Ying-chao Hu ◽  
Shu Wang ◽  
Jing-he Lang

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Corrine Corrina R. Hartford ◽  
Ashish Lal

ABSTRACT Recent advancements in genetic and proteomic technologies have revealed that more of the genome encodes proteins than originally thought possible. Specifically, some putative long noncoding RNAs (lncRNAs) have been misannotated as noncoding. Numerous lncRNAs have been found to contain short open reading frames (sORFs) which have been overlooked because of their small size. Many of these sORFs encode small proteins or micropeptides with fundamental biological importance. These micropeptides can aid in diverse processes, including cell division, transcription regulation, and cell signaling. Here we discuss strategies for establishing the coding potential of putative lncRNAs and describe various functions of known micropeptides.


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