Expression Patterns Of ncRNAs Research Articles

Extracellular RNAs from Whole Urine to Distinguish Prostate Cancer from Benign Prostatic Hyperplasia.

RNAs, especially non-coding RNAs (ncRNAs), are crucial players in regulating cellular mechanisms due to their ability to interact with and regulate other molecules. Altered expression patterns of ncRNAs have been observed in prostate cancer (PCa), contributing to the disease's initiation, progression, and treatment response. This study aimed to evaluate the ability of a specific set of RNAs, including long ncRNAs (lncRNAs), microRNAs (miRNAs), and mRNAs, to discriminate between PCa and the non-neoplastic condition benign prostatic hyperplasia (BPH). After selecting by literature mining the most relevant RNAs differentially expressed in biofluids from PCa patients, we evaluated their discriminatory power in samples of unfiltered urine from 50 PCa and 50 BPH patients using both real-time PCR and droplet digital PCR (ddPCR). Additionally, we also optimized a protocol for urine sample manipulation and RNA extraction. This two-way validation study allowed us to establish that miRNAs (i.e., miR-27b-3p, miR-574-3p, miR-30a-5p, and miR-125b-5p) are more efficient biomarkers for PCa compared to long RNAs (mRNAs and lncRNAs) (e.g., PCA3, PCAT18, and KLK3), as their dysregulation was consistently reported in the whole urine of patients with PCa compared to those with BPH in a statistically significant manner regardless of the quantification methodology performed. Moreover, a significant increase in diagnostic performance was observed when molecular signatures composed of different miRNAs were considered. Hence, the abovementioned circulating ncRNAs represent excellent potential non-invasive biomarkers in urine capable of effectively distinguishing individuals with PCa from those with BPH, potentially reducing cancer overdiagnosis.

Whole-transcriptome sequencing analysis to identify key circRNAs, miRNAs, and mRNAs in the development of yak testes

BackgroundThe Testis is an important reproductive organ in male mammals and the site for spermatogenesis, androgen synthesis, and secretion. Non-coding RNAs (ncRNAs) play an important regulatory role in various biological processes. However, the regulatory role of ncRNAs in the development of yak testes and spermatogenesis remains largely unclear.ResultIn this study, we compared the expression profiles of circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) in yak testicular tissue samples collected at 6 months (Y6M), 18 months (Y18M), and 4 years (Y4Y). Using RNA sequencing (RNA-Seq), we observed a significant difference in the expression patterns of ncRNAs in the samples collected at different testicular development stages. Twenty-two differentially expressed (DE) circRNAs, 69 DE miRNAs, and 64 DE mRNAs were detected in Y6M, Y18M, and Y4Y testicular samples, respectively. The results of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the source genes of DE circRNAs, predicted target genes of DE miRNAs, and DE mRNAs were specifically associated with signaling pathways and GO terms that were related to sperm synthesis, sperm vitality, and testicular development, such as cell cycle, Wnt signaling pathway, MAPK signaling pathway, GnRH signaling pathway, and spermatogenesis. The analysis of the circRNA-miRNA-mRNA network revealed that some DE ncRNAs, including miR-574, miR-449a, CDC42, and CYP11A1, among others, may be involved in testicular spermatogenesis. Concurrently, various circRNA-miRNA interaction pairs were observed.ConclusionOur findings provide a database of circRNAs, miRNAs, and mRNAs expression profiles in testicular tissue of yaks at different developmental stages and a detailed understanding of the regulatory network of ncRNAs in yak testicular development and provide data that can help elucidate the molecular mechanisms underlying yak testicular development.

The Expression Patterns of Non-Coding RNAs in Periodontal Disease.

During the last few decades there has been a growing interest in understanding the involvement of epigenetics in the pathogenesis and treatment of periodontal disease. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), may serve as epigenetic modifiers affecting the expression of genes involved in the pathogenesis of inflammatory and autoimmune diseases. There is increasing evidence supporting the idea that the function of all three types of ncRNAs seems to be interdependent. LncRNAs can act as miRNA decoys, while circRNAs can act as miRNA sponges, leading to the re-expression of miRNA target genes. The purpose of this review is to evaluate the expression patterns of ncRNAs in periodontal disease. Studies demonstrate a positive correlation between miRNA expression and periodontitis; however, this cannot be claimed for lncRNAs and circRNAs, which appear to be differentially expressed in periodontitis patients. Several studies have also suggested utilizing ncRNAs as diagnostic and prognostic biomarkers in periodontitis, or even as potential therapeutic targets; Nevetheless, the evidence to support this is premature. Future well-designed research remains necessary to establish the functional role of ncRNAs in the evolution and progression of periodontal disease.

The Comprehensive Detection of mRNAs, lncRNAs, circRNAs, and miRNAs in Lychee Response to Lychee Downy Blight

Lychee downy blight (LDB) is an oomycete pathogen (Peronophythora litchi) disease, which affects the fruits and leaves of lychee, resulting in economic losses. Chemical fungicides are commonly used for disease control, while for eco-safety measures, the study of molecular mechanisms involved in lychee resistance against LDB is necessary. Non-coding RNAs (ncRNAs), including long ncRNAs (lncRNAs), circular (circRNAs), and microRNAs (miRNAs), play a crucial role in plant disease resistance. To examine lychee response (fruits and leaves) to LDB, we studied the expression patterns of ncRNAs and mRNAs under LDB treatment. By whole transcriptome sequencing analyses, a total of 36,885 mRNAs, 2627 lncRNAs, 4682 circRNAs, and 525 miRNAs were identified in lychee. A differential expression (DE) analysis revealed that there were 1095 DEmRNAs, 89 DElncRNAs, 28 DEcircRNAs, and 28 DEmiRNAs in the LDB-treated fruits, as well as 1158 DEmRNAs, 132 DElncRNAs, 13 DEcircRNAs, and 197 DEmiRNAs in the LDB-treated leaves. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the potential function of DEmRNAs and the targets of ncRNAs were involved in plant defense. Furthermore, co-expression networks of putative interacting ncRNAs and mRNAs were developed, in which mRNAs encoded some receptor proteins, pointing to potential ncRNAs associated with LDB infection. Our study provided a new, brief insight to the putative role of ncRNAs in lychee response to LDB.

Identification of the Genome-Wide Expression Patterns of Non-Coding RNAs Associated with Tanshinones Synthesis Pathway in Salvia miltiorrhiza

The red root of Salvia miltiorrhiza Bunge, a famous traditional Chinese medicine (TCM), was caused by tanshinone in epidermis cells. In order to study the biological function of ncRNAs in the tanshinone synthesis, the expression patterns of mRNA and ncRNAs were comprehensively analyzed in red (high tanshinone content) and white root (low tanshinone content) tissues derived from the same plant. A total of 731 differentially expressed genes (DEGs) were mainly enriched in primary metabolic pathways such as galactose and nitrogen, and some secondary metabolic pathways such as phenylpropanoid and terpenoids. A total of 70 miRNAs, 48 lncRNAs, and 26 circRNAs were identified as differentially expressed (DE) ones. The enrichment pathway of the targets of DE-lncRNA were mainly in ribosome, carbon metabolism, plant hormone signal transduction, and glycerophospholipid metabolism. The function of the targets genes of 59 miRNAs combined with DE-circRNAs was mainly involved in plant–pathogen interaction, endocytosis, phenylpropanoid biosynthesis, and sesquiterpenoid and triterpenoid biosynthesis pathways. Most genes of the tanshinone synthesis pathway had a higher expression. Some ncRNAs were predicted to regulate several key enzyme genes of the tanshinone synthesis pathway, such as SmDXS2, SmGGPPS1, SmKSL. Furthermore, most target genes were related to the resistance of pathogens. The present study exhibited the tissue-specific expression patterns of ncRNAs, which would provide a basis for further research into the regulation mechanism of ncRNAs in the tanshinone synthesis process.

CeRNA crosstalk mediated by ncRNAs is a novel regulatory mechanism in fish sex determination and differentiation.

Competing endogenous RNAs (ceRNAs) are vital regulators of gene networks in mammals. The involvement of noncoding RNAs (ncRNAs) as ceRNA in genotypic sex determination (GSD) and environmental sex determination (ESD) in fish is unknown. The Chinese tongue sole, which has both GSD and ESD mechanisms, was used to map the dynamic expression pattern of ncRNAs and mRNA in gonads during sex determination and differentiation. Transcript expression patterns shift during the sex differentiation phase, and ceRNA modulation occurs through crosstalk of differentially expressed long ncRNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and sex-related genes in fish. Of note was the significant up-regulation of a circRNA from the sex-determining gene dmrt1 (circular RNA dmrt1) and a lncRNA, called AMSDT (which stands for associated with male sex differentiation of tongue sole) in Chinese tongue sole testis. These two ncRNAs both share the same miRNA response elements with gsdf, which has an up-regulated expression when they bind to miRNA cse-miR-196 and concurrent down-regulated female sex-related genes to facilitate testis differentiation. This is the first demonstration in fish that ceRNA crosstalk mediated by ncRNAs modulates sexual development and unveils a novel regulatory mechanism for sex determination and differentiation.

Expanding Roles of Noncoding RNAs in the Pathogenesis of Systemic Lupus Erythematosus.

The exact pathogenesis of systemic lupus erythematosus (SLE) remains unclear. Accumulating finds have indicated the roles of the non-coding RNAs (ncRNAs) acting as novel epigenetic regulatory elements in the dysfunction of the immune system in SLE. This review will introduce recent studies on how ncRNAs are involved in the development of SLE. Recent advances in ncRNAs biology have greatly expanded our understanding of epigenetic regulation of immune responses and inflammation, and increasing evidence suggests ncRNAs are important players in SLE development. Identifications of abnormal expression patterns of ncRNAs and relevant biological impacts in lupus patients have revealed their potential as novel biomarkers and therapeutic targets for SLE. The dysregulation of ncRNAs contributes to the immunopathogenesis of SLE. Clarifying the functions and mechanisms of SLE-associated ncRNAs provides new opportunities for disease biomarkers and targeted therapies.

Role of Fasciola hepatica Small RNAs in the Interaction With the Mammalian Host.

MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression being involved in many different biological processes and play a key role in developmental timing. Additionally, recent studies have shown that miRNAs released from parasites are capable of regulating the expression of host genes. In the present work, we studied the expression patterns of ncRNAs of various intra-mammalian life-cycle stages of the liver fluke, Fasciola hepatica, as well as those packaged into extracellular vesicles and shed by the adult fluke. The miRNA expression profile of the intra-mammalian stages shows important variations, despite a set of predominant miRNAs that are highly expressed across all stages. No substantial variations in miRNA expression between dormant and activated metacercariae were detected, suggesting that they might not be central players in regulating fluke gene expression during this crucial step in the invasion of the definitive host. We generated a curated pipeline for the prediction of putative target genes that reports only sites conserved between three different prediction approaches. This pipeline was tested against an iso-seq curated database of the 3’ UTR regions of F. hepatica genes to detect miRNA regulation networks within liver fluke. Several functions related to the host immune response or modulation were enriched among the targets of the most highly expressed parasite miRNAs, stressing that they might be key players during the establishment and maintenance of infection. Additionally, we detected fragments derived from the processing of tRNAs, in all developmental stages analyzed, and documented the presence of novel long tRNA fragments enriched in vesicles. We confirmed the presence of at least 5 putative vault RNAs (vtRNAs), that are expressed across different stages and enriched in vesicles. The presence of tRNA fragments and vtRNAs in vesicles raise the possibility that they could be involved in the host-parasite interaction.

A genome-wide expression profile of noncoding RNAs in human osteosarcoma cells as they acquire resistance to cisplatin

BackgroundRecurrence after cisplatin therapy is one of the major hindrances in the management of cancer. This necessitates a deeper understanding of the molecular signatures marking the acquisition of resistance. We therefore modeled the response of osteosarcoma (OS) cells to the first-line chemotherapeutic drug cisplatin. A small population of nondividing cells survived acute cisplatin shock (persisters; OS-P). These cells regained proliferative potential over time re-instating the population again (extended persisters; OS-EP).ResultIn this study, we present the expression profile of noncoding RNAs in untreated OS cells (chemo-naive), OS-P, OS-EP and drug-resistant (OS-R) cells derived from the latter. RNA sequencing was carried out, and thereafter, differential expression (log2-fold ± 1.5; p value ≤ 0.05) of microRNAs (miRNAs) was analyzed in each set. The core set of miRNAs that were uniquely or differentially expressed in each group was identified. Interestingly, we observed that most of each group had their own distinctive set of miRNAs. The miRNAs showing an inverse correlation in expression pattern with mRNAs were further selected, and the key pathways regulated by them were delineated for each group. We observed that pathways such as TNF signaling, autophagy and mitophagy were implicated in multiple groups.ConclusionTo the best of our knowledge, this is the first study that provides critical information on the variation in the expression pattern of ncRNAs in osteosarcoma cells and the pathways that they might tightly regulate as cells acquire resistance.

From Micro to Long: Non-Coding RNAs in Tamoxifen Resistance of Breast Cancer Cells.

Simple SummaryBreast cancer is a disease that affects thousands of women around the world. Adequate treatment depends on the characterization of breast cancer subtypes. Tumors that are positive for the estrogen receptor represent the most common subtypes and have the best prognosis. However, many patients relapse due to resistance to tamoxifen, one of the main drugs used for these subtypes. In this study, our goal is to discuss a class of molecules that have been directly linked to the tamoxifen resistance process but is still underexplored: the non-coding RNAs (ncRNAs). We have reviewed ncRNAs that have been associated with different processes of resistance to tamoxifen in order to stimulate a discussion about the importance of knowing and understanding the role of these molecules in breast cancer and their relevance to clinical applications.Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer mortality among women. Two thirds of patients are classified as hormone receptor positive, based on expression of estrogen receptor alpha (ERα), the main driver of breast cancer cell proliferation, and/or progesterone receptor, which is regulated by ERα. Despite presenting the best prognosis, these tumors can recur when patients acquire resistance to treatment by aromatase inhibitors or antiestrogen such as tamoxifen (Tam). The mechanisms that are involved in Tam resistance are complex and involve multiple signaling pathways. Recently, roles for microRNAs and lncRNAs in controlling ER expression and/or tamoxifen action have been described, but the underlying mechanisms are still little explored. In this review, we will discuss the current state of knowledge on the roles of microRNAs and lncRNAs in the main mechanisms of tamoxifen resistance in hormone receptor positive breast cancer. In the future, this knowledge can be used to identify patients at a greater risk of relapse due to the expression patterns of ncRNAs that impact response to Tam, in order to guide their treatment more efficiently and possibly to design therapeutic strategies to bypass mechanisms of resistance.

Novel Non-coding RNA Analysis in Multiple Myeloma Identified Through High-Throughput Sequencing.

This study aimed to explore the potential effects of novel non-coding ribose nucleic acids (ncRNAs) in patients with multiple myeloma (MM). The gene expression profile of plasma cells was used for sequence analysis to explore the expression pattern of ncRNAs in MM. The expression patterns of non-coding RNAs in MM were analyzed by RNA sequencing (whole-transcriptome-specific RNA sequencing). Next, the expression of the selected ncRNAs was verified by quantitative real-time polymerase chain reaction. Further, the lncRNA-associated competitive endogenous RNA network in MM was elucidated using deep RNA-seq. Differentially expressed (DE) ncRNAs were significantly regulated in patients with MM. DE target lncRNAs were analyzed by cis and trans targeting prediction. Two new lncRNAs were shown to be related to MM oncogenes. MSTRG.155519 played a carcinogenic role in myeloma by targeting CEACAM1; MSTRG.13132 was related to FAM46C. Finally, the network of lncRNA–mRNA–miRNA in MM was constructed in this study. The expression of non-coding RNAs through sequence and functional analyses might be helpful for further studies on the pathogenesis of MM and the development of new MM-targeted therapy for non-coding RNAs.

Emerging roles of non‑coding RNAs in the response of rectal cancer to radiotherapy (Review).

Radiotherapy (RT) followed by radical surgery is an effective standard treatment strategy for various types of cancer, including rectal cancer. The response to RT varies among patients, and the radiosensitivity of cancer cells determines the clinical outcome of patients. However, the application of RT to patients with radioresistant tumors may result in radiation‑induced toxicity without clinical benefits. Currently, there are no effective methods to predict the response to RT. The limitations of the methods currently used to evaluate tumor radiosensitivity, which are mainly based on clinical and radiological features, are low sensitivity and specificity. Non‑coding RNAs (ncRNAs) have emerged as a class of biomarkers for predicting radiosensitivity. In particular, the expression pattern of ncRNAs can predict the response to RT in patients with rectal cancer. Thus, ncRNAs may be used as potential biomarkers and therapeutic targets to improve the diagnosis and treatment outcome of patients with rectal cancer. In the present review, the current knowledge on the limitations of RT for rectal cancer and the association between ncRNA expression and sensitivity of rectal cancer to RT are presented. Additionally, the potential of ncRNAs as predictive biomarkers and therapeutic targets to mitigate resistance of rectal cancer to RT is discussed.

The regulated profile of noncoding RNAs associated with inflammation by tanshinone IIA on atherosclerosis.

Atherosclerosis (AS) is the principal cause of heart attack, sudden cardiac death, stroke, and necrosis of the extremities, in which significant changes in gene expression associated with inflammation are found. However, the molecular mechanisms of AS are not clearly elucidated. In this study, ApoE-/- mice were fed with a high fat diet for 12weeks to induce atherosclerosis and half of the mice were treated with tanshinone IIA (TAN). Then sequencing analysis was performed to investigate the expression patterns of ncRNAs in AS plaques obtained from mice treated with TAN and AS Model mice. A total of 22 long noncoding RNAs (lncRNAs), 74 microRNAs (miRNAs), 13 circular RNAs (circRNAs), and 1359 mRNAs in AS plaque were more significantly regulated from TAN mice, compared with model mice. Bioinformatics tools and databases were employed to investigate the potential ncRNA functions and their interaction. Our data showed that the most significantly pathways regulated by TAN were associated with inflammation, and involved in the signaling pathways of Ras, Rap1, MAPK, cAMP, T cell receptor, and so on. In addition, the competitive endogenous RNA (ceRNA) network had been constructed and the core nodes included circ-Tns3/let-7d-5p/Ctsl, circ-Wdr91/miR-378a-5p/Msr1, and circ-Cd84/ miR-30c/ Tlr2. The DERNAs were validated by quantitative RT-PCR and dual luminescence reporter assay in RAW264.7 cells in vitro. This study identified ceRNAs network regulated by TAN and elucidated the ncRNAs profile and signal pathways to attenuate AS comprehensively. This research would contribute to further research on the pathogenesis of AS, and facilitate the development of novel therapeutics targeting ncRNAs.

Trends of non-coding RNAs research in acute rejection after kidney transplantation

The success of kidney transplantation as the treatment of choice for patients with end-stage kidney diseases (ESKD) is hindered by eventual failure of grafts mainly due to immune mediated rejection. Early detection of acute rejection (AR) for early initiation of proper anti-rejection therapy is very important in preventing allograft damage or loss. Understanding of non-coding RNAs’ (ncRNAs) function and the existence of a highly regulated interplay between mRNA/miRNAs/lncRNAs in allograft rejection has gained the attention of research groups to explore different expression patterns of ncRNAs in the field of organ transplantation. Finding a specific pattern of ncRNAs as biomarker will be extremely important for monitoring the kidney allograft function, diagnosis, treatment and even preventing of AR occurrence. In this review list of miRNAs and lncRNAs have been linked to AR following kidney transplantation until now is presented.

MicroRNAs and other non-coding RNAs in adipose tissue and obesity: emerging roles as biomarkers and therapeutic targets.

Obesity is a metabolic condition usually accompanied by insulin resistance (IR), type 2 diabetes (T2D), and dyslipidaemia, which is characterised by excessive fat accumulation and related to white adipose tissue (WAT) dysfunction. Enlargement of WAT is associated with a transcriptional alteration of coding and non-coding RNAs (ncRNAs). For many years, big efforts have focused on understanding protein-coding RNAs and their involvement in the regulation of adipocyte physiology and subsequent role in obesity. However, diverse findings have suggested that a dysfunctional adipocyte phenotype in obesity might be also dependent on specific alterations in the expression pattern of ncRNAs, such as miRNAs. The aim of this review is to update current knowledge on the physiological roles of miRNAs and other ncRNAs in adipose tissue function and their potential impact on obesity. Therefore, we examined their regulatory role on specific WAT features: adipogenesis, adipokine secretion, inflammation, glucose metabolism, lipolysis, lipogenesis, hypoxia and WAT browning. MiRNAs can be released to body fluids and can be transported (free or inside microvesicles) to other organs, where they might trigger metabolic effects in distant tissues, thus opening new possibilities to a potential use of miRNAs as biomarkers for diagnosis, prognosis, and personalisation of obesity treatment. Understanding the role of miRNAs also opens the possibility of using these molecules on individualised dietary strategies for precision weight management. MiRNAs should be envisaged as a future therapeutic approach given that miRNA levels could be modulated by synthetic molecules (f.i. miRNA mimics and inhibitors) and/or specific nutrients or bioactive compounds.

Systematic analysis of the expression profile of non-coding RNAs involved in ischemia/reperfusion-induced acute kidney injury in mice using RNA sequencing.

Acute kidney injury (AKI) is a common and serious disease characterized by a rapid decline in renal function and has an unacceptably high mortality rate with no effective treatment beyond supportive care. AKI can be induced by many factors such as ischemia/reperfusion (IR), sepsis, and drug-induced nephrotoxicity. However, the molecular mechanisms of AKI are poorly understood. A non-coding RNA (ncRNA) is a RNA molecule that is not translated into a protein. NcRNAs play multiple roles in cellular processes, and mutations or imbalances of these molecules within the body can cause a variety of diseases. Although growing evidence has supported the key role of ncRNAs in AKI, the specific mechanism remains largely unknown. In this study, the second-generation gene sequencing was performed to investigate the expression patterns of ncRNAs, including microRNA (miRNA), long non-coding RNAs, and circular RNAs, in the kidneys of mice subjected to IR-induced AKI. This information will contribute to future research of the mechanism of ncRNAs in the pathogenesis of AKI and facilitate the identification of novel therapeutic targets of ncRNAs.

Identification of the Spinal Expression Profile of Non-coding RNAs Involved in Neuropathic Pain Following Spared Nerve Injury by Sequence Analysis.

Neuropathic pain (NP) is caused by damage to the nervous system, resulting in aberrant pain, which is associated with gene expression changes in the sensory pathway. However, the molecular mechanisms are not fully understood. A non-coding Ribose Nucleic Acid (ncRNA) is an RNA molecule that is not translated into a protein. NcRNAs are involved in many cellular processes, and mutations or imbalances of the repertoire within the body can cause a variety of diseases. Although ncRNAs have recently been shown to play a role in NP pathogenesis, the specific effects of ncRNAs in NP remain largely unknown. In this study, sequencing analysis was performed to investigated the expression patterns of ncRNAs in the spinal cord following spared nerve injury-induced NP. A total of 134 long non-coding RNAs (lncRNAs), 12 microRNAs (miRNAs), 188 circular RNAs (circRNAs) and 1066 mRNAs were significantly regulated at 14 days after spared nerve injury (SNI) surgery. Next, quantitative real-time polymerase chain reaction (PCR) was performed to validate the expression of selected lncRNAs, miRNAs, circRNAs, and mRNAs. Bioinformatics tools and databases were employed to explore the potential ncRNA functions and relationships. Our data showed that the most significantly involved pathways in SNI pathogenesis were ribosome, PI3K-Akt signaling pathway, focal adhesion, ECM-receptor interaction, amoebiasis and protein digestion and absorption. In addition, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA network of NP was constructed. This is the first study to comprehensively identify regulated ncRNAs of the spinal cord and to demonstrate the involvement of different ncRNA expression patterns in the spinal cord of NP pathogenesis by sequence analysis. This information will enable further research on the pathogenesis of NP and facilitate the development of novel NP therapeutics targeting ncRNAs.

Non-coding RNAs: emerging regulatory factors in the derivation and differentiation of mammalian parthenogenetic embryonic stem cells.

Parthenogenetic embryonic stem cells (PESCs) are ESCs derived from early parthenogenetic embryos. Haploid PESCs, containing haploid DNA, originate from a single sperm or occyte, while, diploid PESCs originate from two fused occytes. Most PESC lines used so far are diploid. PESCs exhibit representative pluripotent stem cell features, such as the capacity for self-renewal and the pariticular molecular signatures. Whereas, PESCs display distinctive properties, such as differential regulation of X-chromosome inactivation (XCI) and divergent monitor of genes involved in multiple biological processes. PESCs are considered promising in the regeneration medicine and developmental biology. Non-coding RNAs (ncRNAs), especially miRNAs and lncRNAs, have garnered increasing attention over the past 2 decades. They are now known to be involved in almost all cellular processes due to their full-range regulation of gene expression. Numerous studies have indicated that embryonic stem cells (ESCs) displayed distinct signatures of ncRNA genes, which play key roles in the pluripotency and self renewal of ESCs. However, the expression pattern of ncRNAs in PESCs and their roles in the derivation and differentiation of PESCs were rarely reported. In this paper, we reviewed recent research on the derivation and differentiation of PESCs and describe the emerging role of ncRNAs in these processes.

Implications of non-coding RNAs in viral infections.

The advances in RNA sequencing have unveiled various non-coding RNAs (ncRNAs), which modulate the gene expression. ncRNAs do not get translated into proteins. These include transfer RNAs, ribosomal RNAs, microRNA (miRNA), short interfering RNA, long non-coding RNA, piwi-interacting RNA and small nuclear RNA. ncRNAs regulate gene expression at various levels and control cellular machinery. miRNAs have been reported in plants, animals, several invertebrates and viruses. The miRNAs regulate the gene expression post-transcriptionally. Viral infection strongly influences the abundance and the distribution of miRNAs and other ncRNAs within the host cells. Viruses may encode their own miRNA, which help in the viral life cycle and other aspects of pathogenesis. Viruses are known to successfully modulate the expression pattern of ncRNAs. The ncRNA-based strategies adopted by viruses for their survival present a complex picture of host-virus interactions. Copyright © 2016 John Wiley & Sons, Ltd.

Long non-coding RNAs in hematologic malignancies: road to translational research

The human genome encodes ~20,000 proteins; however, protein-coding genes represent <2% of the total genome (Gibb et al., 2011). Since this discovery, several studies have pointed out that at least 90% of the genome is actively transcribed (Birney et al., 2007; Costa, 2010). This field provoked a spirited debate, which is evident from the number of original articles, reviews, letter to the editors, commentaries, and rebuttals. Many long non-coding RNAs (lncRNAs), ranging from 0.2 to ~100 kilobases (kb) in length, are transcribed from the genome. LncRNAs affect various cellular functions such as gene regulation, genomic imprinting, RNA maturation, and translation (Wang and Chang, 2011). In addition, the differential expression of lncRNAs has recently been linked to carcinogenesis, including gastric cancer (Hajjari et al., 2013). In recent reports, lncRNAs have been attributed to oncogenic and/or tumor suppressor roles (Reviewed in Gibb et al., 2011; Qiu et al., 2013). Taken together, these reports support the possible involvement of lncRNAs in the initiation and/or progression of breast, colorectal, liver, lung, and gastric cancers (Hajjari and Khoshnevisan, 2013). However, little is known about the potential role of lncRNAs in leukemia. In fact, there is a paucity of reports on the characterization of lncRNAs in this type of cancer. In the December 2011 edition of Frontiers in Genetics, Heuston et al. (2011) published a review on non-coding RNAs in hematologic malignancies. They highlighted the potential roles for non-coding RNAs including microRNAs and lncRNAs in the development of acute and chronic leukemia. While this is the only review that described the expression patterns of ncRNAs in leukemia, it may provide a foundation for future research in this field. Heuston et al., referred to several reports on lncRNAs such as ANRIL, lncRNA-P21, MEG3, Dleu2, HOTAIRM1, EGO, and lncRNA-a7 in leukemia, highlighting the potential benefit of research on lncRNAs for the development of much needed diagnostic, prognostic, and therapeutic targets (Heuston et al., 2011). In addition, based on the previous studies, Heuston et al., proposed to study more about the functional role of MEG3 in leukemia. In our opinion, this review provides an overview of the published reports on the subject and represents a suitable guide for researchers involved in the field of molecular pathology of leukemia. To test if any prior evidence on the potential role of lncRNAs in leukemia progression existed, we queried the Oncomine Database (www.oncomine.org) for five lncRNAs: HOTAIR, ANRIL, MEG3, H19, and UCA1. All five lncRNAs were among the most cited lncRNAs associated with a potential role in cancer. We found that two lncRNAs including MEG3 and H19 are up-regulated in acute myeloid leukemia (AML) cancer compared to normal blood cells (Fold change > 1.5, P-value < 0.01). As presented in Table ​Table1,1, the results showed that H19, UCA1, and MEG3 are up-regulated in French-American-British (FAB) classification subtypes M3, M2, and M3, respectively. The expression of H19 is up-regulated in AML compared to acute lymphoblastic leukemia (ALL). In conclusion, taken together, the review from Heuston et al. and our data shed lights on the roles of lncRNAs in different types of leukemia and may prove useful for the development of molecular diagnosis and targeted therapy for leukemia. Table 1 Expression level of the lncRNAs in Leukemia (the results are expressed as fold change between cancer and normal tissues or cancer subtypes).