scholarly journals Non-Coding RNAs in Breast Cancer: Intracellular and Intercellular Communication

2018 ◽  
Vol 4 (4) ◽  
pp. 40 ◽  
Author(s):  
Carolyn Klinge

Non-coding RNAs (ncRNAs) are regulators of intracellular and intercellular signaling in breast cancer. ncRNAs modulate intracellular signaling to control diverse cellular processes, including levels and activity of estrogen receptor α (ERα), proliferation, invasion, migration, apoptosis, and stemness. In addition, ncRNAs can be packaged into exosomes to provide intercellular communication by the transmission of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) to cells locally or systemically. This review provides an overview of the biogenesis and roles of ncRNAs: small nucleolar RNA (snRNA), circular RNAs (circRNAs), PIWI-interacting RNAs (piRNAs), miRNAs, and lncRNAs in breast cancer. Since more is known about the miRNAs and lncRNAs that are expressed in breast tumors, their established targets as oncogenic drivers and tumor suppressors will be reviewed. The focus is on miRNAs and lncRNAs identified in breast tumors, since a number of ncRNAs identified in breast cancer cells are not dysregulated in breast tumors. The identity and putative function of selected lncRNAs increased: nuclear paraspeckle assembly transcript 1 (NEAT1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), steroid receptor RNA activator 1 (SRA1), colon cancer associated transcript 2 (CCAT2), colorectal neoplasia differentially expressed (CRNDE), myocardial infarction associated transcript (MIAT), and long intergenic non-protein coding RNA, Regulator of Reprogramming (LINC-ROR); and decreased levels of maternally-expressed 3 (MEG3) in breast tumors have been observed as well. miRNAs and lncRNAs are considered targets of therapeutic intervention in breast cancer, but further work is needed to bring the promise of regulating their activities to clinical use.

2021 ◽  
Vol 7 (1) ◽  
pp. 2
Author(s):  
Debina Sarkar ◽  
Sarah D. Diermeier

Circular RNAs (circRNAs) are a class of non-coding RNAs that form a covalently closed loop. A number of functions and mechanisms of action for circRNAs have been reported, including as miRNA sponge, exerting transcriptional and translational regulation, interacting with proteins, and coding for peptides. CircRNA dysregulation has also been implicated in many cancers, such as breast cancer. Their relatively high stability and presence in bodily fluids makes cancer-associated circRNAs promising candidates as a new biomarker. In this review, we summarize the research undertaken on circRNAs associated with breast cancer, discuss circRNAs as biomarkers, and present circRNA-based therapeutic approaches.


Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3530
Author(s):  
Penn Muluhngwi ◽  
Carolyn M. Klinge

Despite improvements in the treatment of endocrine-resistant metastatic disease using combination therapies in patients with estrogen receptor α (ERα) primary tumors, the mechanisms underlying endocrine resistance remain to be elucidated. Non-coding RNAs (ncRNAs), including microRNAs (miRNA) and long non-coding RNAs (lncRNA), are targets and regulators of cell signaling pathways and their exosomal transport may contribute to metastasis. Previous studies have shown that a low expression of miR-29a-3p and miR-29b-3p is associated with lower overall breast cancer survival before 150 mos. Transient, modest overexpression of miR-29b1-3p or miR-29a-3p inhibited MCF-7 tamoxifen-sensitive and LCC9 tamoxifen-resistant cell proliferation. Here, we identify miR-29b-1/a-regulated and non-regulated differentially expressed lncRNAs in MCF-7 and LCC9 cells using next-generation RNA seq. More lncRNAs were miR-29b-1/a-regulated in LCC9 cells than in MCF-7 cells, including DANCR, GAS5, DSCAM-AS1, SNHG5, and CRND. We examined the roles of miR-29-regulated and differentially expressed lncRNAs in endocrine-resistant breast cancer, including putative and proven targets and expression patterns in survival analysis using the KM Plotter and TCGA databases. This study provides new insights into lncRNAs in endocrine-resistant breast cancer.


2021 ◽  
Vol 22 ◽  
Author(s):  
Vandana Golhani ◽  
Suman Kumar Ray ◽  
Sukhes Mukherjee

: MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are proficient in regulating gene expression post-transcriptionally. Considering the recent trend in exploiting non-coding RNAs (ncRNAs) as cancer therapeutics, the potential use of miRNAs and lncRNAs as biomarkers and novel therapeutic agents against angiogenesis is an important scientific aspect. An estimated 70% of the genome is actively transcribed, only 2% of which codes for known protein-coding genes. Long noncoding RNAs (lncRNAs) are a large and diverse class of RNAs > 200 nucleotides in length, and not translated into protein, and are of utmost importance and it governs the expression of genes in a temporal, spatial, and cell context-dependent manner. Angiogenesis is an essential process for organ morphogenesis and growth during development, and it is relevant during the repair of wounded tissue in adults. It is coordinated by an equilibrium of pro-and anti-angiogenic factors; nevertheless, when affected, it promotes several diseases, including breast cancer. Signaling pathways involved here are tightly controlled systems that regulate the appropriate timing of gene expression required for the differentiation of cells down a particular lineage essential for proper tissue development. Lately, scientific reports are indicating that ncRNAs, such as miRNAs, and lncRNAs, play critical roles in angiogenesis related to breast cancer. The specific roles of various miRNAs and lncRNAs in regulating angiogenesis in breast cancer, with particular focus on the downstream targets and signaling pathways regulated by these ncRNAs with molecular medicine perspective, are highlighted in this write-up.


Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 472
Author(s):  
Silvia Di Agostino

Long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), micro RNAs (miRNAs), and extracellular RNAs (exRNAs) are new groups of RNAs with regulation activities that have low or no protein-coding ability. Emerging evidence suggests that deregulated expression of these non-coding RNAs is associated with the induction and progression of diverse tumors throughout epigenetic, transcriptional, and post-transcriptional modifications. A consistent number of non-coding RNAs (ncRNAs) has been shown to be regulated by p53, the most important tumor suppressor of the cells frequently mutated in human cancer. It has been shown that some mutant p53 proteins are associated with the loss of tumor suppressor activity and the acquisition of new oncogenic functions named gain-of-function activities. In this review, we highlight recent lines of evidence suggesting that mutant p53 is involved in the expression of specific ncRNAs to gain oncogenic functions through the creation of a complex network of pathways that influence each other.


2021 ◽  
Vol 11 ◽  
Author(s):  
Soudeh Ghafouri-Fard ◽  
Tayyebeh Khoshbakht ◽  
Mohammad Taheri ◽  
Elena Jamali

Circular RNAs (circRNAs) are a group of long non-coding RNAs with enclosed structure generated by back-splicing events. Numerous members of these transcripts have been shown to affect carcinogenesis. Circular RNA itchy E3 ubiquitin protein ligase (circITCH) is a circRNA created from back splicing events in ITCH gene, a protein coding gene on 20q11.22 region. ITCH has a role as a catalyzer for ubiquitination through both proteolytic and non-proteolytic routes. CircITCH is involved in the pathetiology of cancers through regulation of the linear isoform as well as serving as sponge for several microRNAs, namely miR-17, miR-224, miR-214, miR-93-5p, miR-22, miR-7, miR-106a, miR-10a, miR-145, miR-421, miR-224-5p, miR-197 and miR-199a-5p. CircITCH is also involved in the modulation of Wnt/β-catenin and PTEN/PI3K/AKT pathways. Except from a single study in osteosarcoma, circITCH has been found to exert tumor suppressor role in diverse cancers. In the present manuscript, we provided a comprehensive review of investigations that reported function of circITCH in the carcinogenesis.


2014 ◽  
Author(s):  
Yongsheng Li ◽  
Yunpeng Zhang ◽  
Shengli Li ◽  
Jianping Lu ◽  
Juan Chen ◽  
...  

The development of human breast cancer is driven by changes in the genetic and epigenetic landscape of the cell. Despite growing appreciation of the importance of epigenetics in breast cancers, our knowledge of epigenetic alterations of non-coding RNAs (ncRNAs) in breast cancers remains limited. Here, we explored the epigenetic patterns of ncRNAs in breast cancers via a sequencing-based comparative methylome analysis, mainly focusing on two most popular ncRNA biotypes, long non-coding RNAs (lncRNAs) and miRNAs. Besides global hypomethylation and extensive CpG islands (CGIs) hypermethylation, we observed widely aberrant methylation in the promoters of ncRNAs, which was higher than that of protein-coding genes. Specifically, intergenic ncRNAs were observed to contribute a large slice of the aberrantly methylated ncRNA promoters. Moreover, we summarized five patterns of ncRNA promoter aberrant methylation in the context of genomic CGIs, where aberrant methylation occurred not only on the CGIs, but also flanking regions and CGI sparse promoters. Integration with transcriptional datasets, we found that the ncRNA promoter methylation events were associated with transcriptional changes. Furthermore, a panel of ncRNAs were identified as biomarkers that were able to discriminate between disease phenotypes (AUCs>0.90). Finally, the potential functions for aberrantly methylated ncRNAs were predicted based on similar patterns, adjacency and/or target genes, highlighting that ncRNAs and coding genes coordinately mediated pathways dysregulation in the development and progression of breast cancers. This study presents the aberrant methylation patterns of ncRNAs, which will be a highly valuable resource for investigations at understanding epigenetic regulation of breast cancers.


2021 ◽  
Vol 12 ◽  
Author(s):  
Bijayalaxmi Sahoo ◽  
Ratan K. Choudhary ◽  
Paramajeet Sharma ◽  
Shanti Choudhary ◽  
Mukesh Kumar Gupta

Livestock production contributes to a significant part of the economy in developing countries. Although artificial insemination techniques brought substantial improvements in reproductive efficiency, male infertility remains a leading challenge in livestock. Current strategies for the diagnosis of male infertility largely depend on the evaluation of semen parameters and fail to diagnose idiopathic infertility in most cases. Recent evidences show that spermatozoa contains a suit of RNA population whose profile differs between fertile and infertile males. Studies have also demonstrated the crucial roles of spermatozoal RNA (spRNA) in spermatogenesis, fertilization, and early embryonic development. Thus, the spRNA profile may serve as unique molecular signatures of fertile sperm and may play pivotal roles in the diagnosis and treatment of male fertility. This manuscript provides an update on various spRNA populations, including protein-coding and non-coding RNAs, in livestock species and their potential role in semen quality, particularly sperm motility, freezability, and fertility. The contribution of seminal plasma to the spRNA population is also discussed. Furthermore, we discussed the significance of rare non-coding RNAs (ncRNAs) such as long ncRNAs (lncRNAs) and circular RNAs (circRNAs) in spermatogenic events.


2020 ◽  
Vol 115 (5) ◽  
Author(s):  
Naisam Abbas ◽  
Filippo Perbellini ◽  
Thomas Thum

Abstract Soon after birth, the regenerative capacity of the mammalian heart is lost, cardiomyocytes withdraw from the cell cycle and demonstrate a minimal proliferation rate. Despite improved treatment and reperfusion strategies, the uncompensated cardiomyocyte loss during injury and disease results in cardiac remodeling and subsequent heart failure. The promising field of regenerative medicine aims to restore both the structure and function of damaged tissue through modulation of cellular processes and regulatory mechanisms involved in cardiac cell cycle arrest to boost cardiomyocyte proliferation. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) are functional RNA molecules with no protein-coding function that have been reported to engage in cardiac regeneration and repair. In this review, we summarize the current understanding of both the biological functions and molecular mechanisms of ncRNAs involved in cardiomyocyte proliferation. Furthermore, we discuss their impact on the structure and contractile function of the heart in health and disease and their application for therapeutic interventions.


Author(s):  
Xiao He ◽  
Tao Xu ◽  
Weijie Hu ◽  
Yufang Tan ◽  
Dawei Wang ◽  
...  

As one of the most frequently occurring malignancies in women, breast cancer (BC) is still an enormous threat to women all over the world. The high mortality rates in BC patients are associated with BC recurrence, metastatic progression to distant organs, and therapeutic resistance. Circular RNAs (circRNAs), belonging to the non-coding RNAs (ncRNAs), are connected end to end to form covalently closed single-chain circular molecules. CircRNAs are widely found in different species and a variety of human cells, with the features of diversity, evolutionary conservation, stability, and specificity. CircRNAs are emerging important participators in multiple diseases, including cardiovascular disease, inflammation, and cancer. Recent studies have shown that circRNAs are involved in BC progress by regulating gene expression at the transcriptional or post-transcriptional level via binding to miRNAs then inhibiting their function, suggesting that circRNAs may be potential targets for early diagnosis, treatment, and prognosis of BC. Herein, in this article, we have reviewed and summarized the current studies about the biogenesis, features, and functions of circRNAs. More importantly, we emphatically elucidate the pivotal functions and mechanisms of circRNAs in BC growth, metastasis, diagnosis, and drug resistance. Deciphering the complex networks, especially the circRNA-miRNA target gene axis, will endow huge potentials in developing therapeutic strategies for combating BC.


2020 ◽  
Vol 20 ◽  
Author(s):  
Mohammad Karim Shahrzad ◽  
Reyhaneh Gharehgozlou ◽  
Sara Fadaei ◽  
Parastoo Hajian ◽  
Hamid Reza Mirzaei

: Breast cancer, a life-threatening serious disease with high incident rate among women, is responsible for thousands of cancer-associated death worldwide. Numerous investigations have been evaluated the possible mechanisms related to this malignancy. Among of them, non-coding RNAs (ncRNAs) i.e., microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs have recently attracted attentions of researchers. In addition to recent studies for evaluating the role of ncRNAs in breast cancer etiology, some investigations have revealed that vitamin D has regulatory and therapeutic roles in breast cancer. Moreover, an important link between vitamin D and ncRNAs in cancer therapy has been highlighted. Herein, we aimed to discuss the available data on mentioned link in breast cancer.


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