Regulatory Non-coding RNAs Research Articles

Noncoding RNA Regulation of Hormonal and Metabolic Systems in the Fruit Fly Drosophila

The importance of RNAs is commonly recognised thanks to protein-coding RNAs, whereas non-coding RNAs (ncRNAs) were conventionally regarded as 'junk'. In the last decade, ncRNAs' significance and roles are becoming noticeable in various biological activities, including those in hormonal and metabolic regulation. Among the ncRNAs: microRNA (miRNA) is a small RNA transcript with ~20 nucleotides in length; long non-coding RNA (lncRNA) is an RNA transcript with >200 nucleotides; and circular RNA (circRNA) is derived from back-splicing of pre-mRNA. These ncRNAs can regulate gene expression levels at epigenetic, transcriptional, and post-transcriptional levels through various mechanisms in insects. A better understanding of these crucial regulators is essential to both basic and applied entomology. In this review, we intend to summarise and discuss the current understanding and knowledge of miRNA, lncRNA, and circRNA in the best-studied insect model, the fruit fly Drosophila.

Brain-enriched miR-128: Reduced in exosomes from Parkinson's patient plasma, improves synaptic integrity, and prevents 6-OHDA mediated neuronal apoptosis.

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the death of mid-brain dopaminergic neurons. Unfortunately, no effective cure or diagnostic biomarkers for PD are available yet. To address this, the present study focuses on brain-enriched small non-coding regulatory RNAs called microRNAs (miRNAs) that are released into the circulation packaged inside small extracellular vesicles called exosomes. We collected blood samples from PD patients and isolated exosomes from the plasma. qPCR-based detection revealed a particular neuron-enriched miR-128 to be significantly decreased in the patient-derived exosomes. Interestingly, a concomitant decreased expression of miR-128 was observed in the cellular models of PD. Fluorescent live cell imaging and flow-cytometry revealed that over-expression of miR-128 can prevent 6-OHDA-mediated mitochondrial superoxide production and induction of neuronal death respectively. This neuroprotective effect was found to be induced by miR-128-mediated inhibition of FoxO3a activation, a transcription factor involved in apoptosis. miR-128 over-expression also resulted in down-regulation of pro-apoptotic FoxO3a targets- FasL and PUMA, at both transcript and protein levels. Further downstream, miR-128 over-expression inhibited activation of caspases-8, -9 and -3, preventing both the intrinsic and extrinsic pathways of apoptosis. Additionally, over expression of miR-128 prevented down-regulation of synaptic proteins- Synaptophysin and PSD-95 and attenuated neurite shortening, thereby maintaining overall neuronal integrity. Thus, our study depicts the intracellular role of miR-128 in neuronal apoptosis and neurodegeneration and its implications as a biomarker being detectable in the circulating exosomes of PD patient blood. Thus, characterization of such exosomal brain-enriched miRNAs hold promise for effective detection and diagnosis of PD.

Epigenetic modifications in esophageal cancer: An evolving biomarker.

Esophageal cancer is a widespread cancer of the digestive system that has two main subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA). In the diverse range of cancer therapy schemes, the side effects of conventional treatments remain an urgent challenge to be addressed. Therefore, the pursuit of novel drugs with multiple targets, good efficacy, low side effects, and low cost has become a hot research topic in anticancer therapy. Based on this, epigenetics offers an attractive target for the treatment of esophageal cancer, where major mechanisms such as DNA methylation, histone modifications, non-coding RNA regulation, chromatin remodelling and nucleosome localization offer new opportunities for the prevention and treatment of esophageal cancer. Recently, research on epigenetics has remained at a high level of enthusiasm, focusing mainly on translating the basic research into the clinical setting and transforming epigenetic alterations into targets for cancer screening and detection in the clinic. With the increasing emergence of tumour epigenetic markers and antitumor epigenetic drugs, there are also more possibilities for anti-esophageal cancer treatment. This paper focuses on esophageal cancer and epigenetic modifications, with the aim of unravelling the close link between them to facilitate precise and personalized treatment of esophageal cancer.

Epigenetic modifications in chronic rhinosinusitis with and without nasal polyps.

Chronic rhinosinusitis (CRS) has brought a huge socioeconomic burden. However, its mechanism is still elusive, which may involve genetic, environmental and some other factors. Epigenetic analyses have been conducted to explore the mechanisms underlying CRS. Here, we reviewed the fruits in the epigenetic studies on DNA methylation, histone modification, and non-coding RNA regulation. We concluded that the epigenetic research on CRS has made great breakthroughs, especially in the past 5years and the field of microRNAs. "Epigenetic therapies" are expected to be designed to treat CRS in the future.

Analysis of a logical regulatory network reveals how Fe-S cluster biogenesis is controlled in the face of stress.

Iron-sulfur (Fe-S) clusters are important cofactors conserved in all domains of life, yet their synthesis and stability are compromised in stressful conditions such as iron deprivation or oxidative stress. Two conserved machineries, Isc and Suf, assemble and transfer Fe-S clusters to client proteins. The model bacterium Escherichia coli possesses both Isc and Suf, and in this bacterium utilization of these machineries is under the control of a complex regulatory network. To better understand the dynamics behind Fe-S cluster biogenesis in E. coli, we here built a logical model describing its regulatory network. This model comprises three biological processes: 1) Fe-S cluster biogenesis, containing Isc and Suf, the carriers NfuA and ErpA, and the transcription factor IscR, the main regulator of Fe-S clusters homeostasis; 2) iron homeostasis, containing the free intracellular iron regulated by the iron sensing regulator Fur and the non-coding regulatory RNA RyhB involved in iron sparing; 3) oxidative stress, representing intracellular H2O2 accumulation, which activates OxyR, the regulator of catalases and peroxidases that decompose H2O2 and limit the rate of the Fenton reaction. Analysis of this comprehensive model reveals a modular structure that displays five different types of system behaviors depending on environmental conditions, and provides a better understanding on how oxidative stress and iron homeostasis combine and control Fe-S cluster biogenesis. Using the model, we were able to predict that an iscR mutant would present growth defects in iron starvation due to partial inability to build Fe-S clusters, and we validated this prediction experimentally.

Epigenetic and epitranscriptomic mechanisms of chromium carcinogenesis.

Hexavalent chromium [Cr(VI)], a Group I carcinogen classified by the International Agency for Research on Cancer (IARC), represents one of the most common occupational and environmental pollutants. The findings from human epidemiological and laboratory animal studies show that long-term exposure to Cr(VI) causes lung cancer and other cancer. Although Cr(VI) is a well-recognized carcinogen, the mechanism of Cr(VI) carcinogenesis has not been well understood. Due to the fact that Cr(VI) undergoes a series of metabolic reductions once entering cells to generate reactive Cr metabolites and reactive oxygen species (ROS) causing genotoxicity, Cr(VI) is generally considered as a genotoxic carcinogen. However, more and more studies have demonstrated that acute or chronic Cr(VI) exposure also causes epigenetic dysregulations including changing DNA methylation, histone posttranslational modifications and regulatory non-coding RNA (microRNA and long non-coding RNA) expressions. Moreover, emerging evidence shows that Cr(VI) exposure is also capable of altering cellular epitranscriptome. Given the increasingly recognized importance of epigenetic and epitranscriptomic dysregulations in cancer initiation and progression, it is believed that Cr(VI) exposure-caused epigenetic and epitranscriptomic changes could play important roles in Cr(VI) carcinogenesis. The goal of this chapter is to review the epigenetic and epitranscriptomic effects of Cr(VI) exposure and discuss their roles in Cr(VI) carcinogenesis. Better understanding the mechanism of Cr(VI) carcinogenesis may identify new molecular targets for more efficient prevention and treatment of cancer resulting from Cr(VI) exposure.

Decoding Cancer Formation: The Impact of Epigenetic Factors

This study delves into the critical role of epigenetic factors in the formation and progression of cancer, offering a comprehensive analysis of the molecular mechanisms that drive tumorigenesis. Epigenetic modifications, including DNA methylation, histone modification, and non-coding RNA regulation, have emerged as key players in the regulation of gene expression without altering the underlying DNA sequence. These modifications can lead to the activation of oncogenes or the silencing of tumor suppressor genes, thereby contributing to the initiation and progression of cancer. The research highlights how disruptions in normal epigenetic processes can result in abnormal cell growth, metastasis, and resistance to apoptosis, which are hallmarks of cancer. By analyzing recent advancements in epigenetic research, the study underscores the importance of understanding these mechanisms to identify potential biomarkers for early cancer detection and to develop targeted therapies that can reverse epigenetic alterations. Through a detailed examination of various cancer types, the study demonstrates the widespread impact of epigenetic changes across different forms of the disease. It also explores the potential of epigenetic therapies, such as inhibitors of DNA methyltransferases and histone deacetylases, in reprogramming cancer cells to a more normal state. This study contributes to the growing body of knowledge on the molecular underpinnings of cancer and offers insights into the development of novel therapeutic strategies that target epigenetic factors, paving the way for more effective and personalized cancer treatments.

Epigenetic regulons in Alzheimer's disease.

Alzheimer's disease is one of the most prevalent forms of dementia that occur genetically or sporadically (with increasing age) in the population of 65 years and above. The pathological hallmarks of AD include the formation of extracellular senile plaques of amyloid beta peptides 42 (Aβ42) and intracellular neurofibrillary tangles associated with hyperphosphorylated tau protein. AD has been reported as an outcome of multiple probabilistic factors such as age, lifestyle, oxidative stress, inflammation, insulin resistance, mitochondrial dysfunction, and epigenetics. Epigenetics are heritable changes in gene expression that give a phenotype without altering the DNA sequences. Epigenetic mechanisms include DNA methylation, hydroxymethylation, histone modifications, regulation of miRNAs and long non-coding RNAs, which are reported to be dysregulated in AD. Further, epigenetic mechanisms have been shown as a key player as they regulate memory development, where DNA methylation and post-translational modifications of histone tails are the prime epigenetic markers. Also, alterations of AD-related genes cause pathogenesis on the transcriptional level. In the current chapter, we summarize the role of epigenetics in the onset and progression of AD and the use of epigenetic therapeutics to ameliorate the constraints of AD.

Changes in the Content of Small Non-Coding RNAs in Spermatozoa as a Possible Mechanism of Transgenerational Transmission of the Effects of Paternal Stress: Experimental Research

It has been proven that the stress of the father can affect the phenotype of offspring, causing somatic, behavioral, hormonal and molecular changes. One of the hypothetical mechanisms responsible for the transmission of paternal effects to offspring may be a change in the spectrum of regulatory non-coding RNAs in spermatozoa. In this paper, we investigated the effect of paternal stress in models of post-traumatic stress disorder (PTSD) and depression on the representation of small RNAs (micro- and piwiRNAs) in the sperm of stressed animals. Male Wistar rats were subjected to stress in two paradigms (“stress–restress” and “learned helplessness”), which leads to the development of PTSD-like and depressive-like states in model animals, respectively. 48 days after the restress, sperm preparations were received and RNA was isolated. The spectrum of small RNAs was studied by NGS sequencing. In males with a PTSD-like condition, a change in the expression of 27 piwi RNAs and 77 microRNAs was detected compared with the control group. Among the targets of these miRNAs, it is possible to identify genes whose products may be involved in such mechanisms of transmission of paternal effects to offspring as changes in DNA methylation, histone modifications and RNA interference (Dnmt3a, Setd5, Hdac1, Mllt10, Mtdh), as well as genes associated with the functioning of insulin-like growth factor 2, the expression of which as previously shown, it is altered in the central nervous system in the offspring of males with a PTSD-like condition (Igf2, Igf2bp2, Igf2r). No changes in the representation of small RNAs were registered in males with a simulated depression-like state. The results indicate a pronounced effect of paternal stress on the spectrum of short non-coding RNAs in sperm cells in rats, however, it depends on the nature of the stress effect.

Databases and prospects of dynamic gene regulation in eukaryotes: A mini review

In eukaryotes, dynamic regulation enables DNA polymerases to catalyze a variety of RNA products in spatial and temporal patterns. Dynamic gene expression is regulated by transcription factors (TFs) and epigenetics (DNA methylation and histone modification). The applications of biochemical technology and high-throughput sequencing enhance the understanding of mechanisms of these regulations and affected genomic regions. To provide a searchable platform for retrieving such metadata, numerous databases have been developed based on the integration of genome-wide maps (e.g., ChIP-seq, whole-genome bisulfite sequencing, RNA-seq, ATAC-seq, DNase-seq, and MNase-seq data) and functionally genomic annotation. In this mini review, we summarize the main functions of TF-related databases and outline the prevalent approaches used in inferring epigenetic regulations, their associated genes, and functions. We review the literature on crosstalk between TF and epigenetic regulation and the properties of non-coding RNA regulation, which are challenging topics that promise to pave the way for advances in database development.

Hypoxia-elicited Exosomes Promote the Chemoresistance of Pancreatic Cancer Cells by Transferring LncROR via Hippo Signaling.

Recent studies have found that hypoxia contributes to tumor progression and drug resistance by inducing the secretion of exosomes. However, the mechanism underlying this resistance in pancreatic cancer remains to be explored. In this study, we investigated the effect of hypoxia-induced tumor-derived exosomes (Hexo) on stemness and resistance to gemcitabine in pancreatic cancer cells, as well as the molecular mechanisms involved in this process. Firstly, we discovered that hypoxia promoted stemness and induced resistance to gemcitabine in pancreatic cancer cells. Secondly, we showed that exosomes secreted by pancreatic cancer cells under normoxic or hypoxic conditions can be transfected into tumor cells. Thirdly, it was demonstrated that Hexo promotes proliferation, stemness, and resistance to gemcitabine in pancreatic cancer cells, as well as inhibits the apoptosis and cell cycle arrest induced by gemcitabine. Finally, it was verified that Hexo inactivated the Hippo/Yes-associated protein (Hippo/YAP) pathway in pancreatic cancer cells by transferring exosomal long non-coding RNA regulator of reprogramming (lncROR). In summary, the hypoxic tumor microenvironment could promote stemness and induce resistance to gemcitabine in pancreatic cancer cells. Mechanistically, Hexo enhanced stemness to promote chemoresistance in pancreatic cancer cells by transferring lncROR via Hippo signaling. Thus, exosomal lncROR may serve as a candidate target of chemotherapy for pancreatic cancer.

New insights into genome annotation in Podospora anserina through re-exploiting multiple RNA-seq data

BackgroundPublicly available RNA-seq datasets are often underused although being helpful to improve functional annotation of eukaryotic genomes. This is especially true for filamentous fungi genomes which structure differs from most well annotated yeast genomes. Podospora anserina is a filamentous fungal model, which genome has been sequenced and annotated in 2008. Still, the current annotation lacks information about cis-regulatory elements, including promoters, transcription starting sites and terminators, which are instrumental to integrate epigenomic features into global gene regulation strategies.ResultsHere we took advantage of 37 RNA-seq experiments that were obtained in contrasted developmental and physiological conditions, to complete the functional annotation of P. anserina genome. Out of the 10,800 previously annotated genes, 5’UTR and 3’UTR were defined for 7554, among which, 3328 showed differential transcriptional signal starts and/or transcriptional end sites. In addition, alternative splicing events were detected for 2350 genes, mostly due alternative 3’splice sites and 1732 novel transcriptionally active regions (nTARs) in unannotated regions were identified.ConclusionsOur study provides a comprehensive genome-wide functional annotation of P. anserina genome, including chromatin features, cis-acting elements such as UTRs, alternative splicing events and transcription of non-coding regions. These new findings will likely improve our understanding of gene regulation strategies in compact genomes, such as those of filamentous fungi. Characterization of alternative transcripts and nTARs paves the way to the discovery of putative new genes, alternative peptides or regulatory non-coding RNAs.

Establishment of an Absolute Quantitative Method to Detect a Plasma tRNA-Derived Fragment and Its Application in the Non-Invasive Diagnosis of Gastric Cancer

(1) Transfer RNA (tRNA)-derived fragments (tRFs) are a new category of regulatory non-coding RNAs with distinct biological functions in cancer. They are produced from pre-tRNAs or mature tRNAs and their sequences are relatively short; thus, the amplification of tRFs, especially those in body fluids, is faced with certain technical difficulties. In this study, we established a quantitative method to detect plasma tRF-27-87R8WP9N1E5 (tRF-27) and used it to screen gastric cancer patients. (2) A specific stem-loop-structure reverse transcription primer, a TaqMan probe, and amplification primers for tRF-27 were prepared, and the absolute quantitative method was used to measure plasma tRF-27 levels. To determine the noninvasive diagnostic value of tRF-27 in gastric cancer, plasma tRF-27 levels in patients with benign and malignant lesions (120 healthy individuals, 48 patients with benign lesions, 48 patients with precancerous lesions, and 72 patients with early gastric cancer) were analyzed. Plasma tRF-27 levels were also analyzed in 106 preoperative gastric cancer patients, 106 postoperative gastric cancer patients, and 120 healthy individuals. Survival curves and Cox regression models were established and analyzed. (3) A new absolute quantitative method to determine the plasma tRF-27 copy number was established. Plasma tRF-27 levels were significantly increased in gastric cancer patients compared to healthy individuals, and the area under the receiver operating characteristic curve was 0.7767, when the cutoff value was 724,807 copies/mL, with sensitivity and specificity values of 0.6226 and 0.8917, respectively. The positive predictive and negative predictive values were 83.50% and 72.80%, respectively. Plasma tRF-27 levels in postoperative gastric cancer patients were significantly decreased compared to preoperative gastric cancer patients and tended to the levels of healthy individuals. Moreover, tRF-27 levels were closely related to tumor size and Ki67 expression in gastric cancer patients. Prognostic analysis showed that tRF-27 may be an independent predictor of overall survival. (4) This novel and non-invasive method of measuring plasma tRF-27 levels was valuable in the early diagnosis of gastric cancer.

Multifunctional Roles of Betulinic Acid in Cancer Chemoprevention: Spotlight on JAK/STAT, VEGF, EGF/EGFR, TRAIL/TRAIL-R, AKT/mTOR and Non-Coding RNAs in the Inhibition of Carcinogenesis and Metastasis.

The pursual of novel anticancer molecules from natural sources has gained worthwhile appreciation, and a significant fraction of conceptual knowledge has revolutionized our understanding about heterogeneous nature of cancer. Betulinic acid has fascinated interdisciplinary researchers due to its tremendous pharmacological properties. Ground-breaking discoveries have unraveled previously unprecedented empirical proof-of-concept about momentous chemopreventive role of betulinic acid against carcinogenesis and metastasis. Deregulation of cell signaling pathways has been reported to play a linchpin role in cancer progression and colonization of metastatically competent cancer cells to the distant organs for the development of secondary tumors. Importantly, betulinic acid has demonstrated unique properties to mechanistically modulate oncogenic transduction cascades. In this mini-review, we have attempted to provide a sophisticated compendium of regulatory role of betulinic acid in cancer chemoprevention. We have partitioned this multi-component review into different sections in which we summarized landmark research-works which highlighted betulinic acid mediated regulation of JAK/STAT, VEGF, EGF/EGFR, TRAIL/TRAIL-R, AKT/mTOR and ubiquitination pathways in the inhibition of cancer. In parallel, betulinic acid mediated regulation of signaling cascades and non-coding RNAs will be critically analyzed in cell culture and animal model studies. Better comprehension of the pharmaceutical features of betulinic acid and mapping of the existing knowledge gaps will be valuable in the translatability of preclinical studies into rationally designed clinical trials.

Differential Expression Analysis of tRNA-Derived Small RNAs from Subcutaneous Adipose Tissue of Obese and Lean Pigs.

Epigenetic factors, including non-coding RNA regulation, play a vital role in the development of obesity and have been well researched. Transfer RNA-derived small RNA (tsRNA) is a class of non-coding RNA proven to be involved in various aspects of mammalian biology. Here we take pigs as a model for obesity research and use tsRNA-seq to investigate the difference in tsRNA expression in the subcutaneous adipose tissue of obese and lean pigs to elucidate the role of tsRNA in obesity development. A total of 482 tsRNAs were identified in pig adipose tissue, of which 123 were significantly differentially accumulated tsRNAs compared with the control group. The tRF-5c was the main type of these tsRNAs. The largest number of tsRNAs produced was the Gly-carrying tRNA, which produced 81 tsRNAs. Functional enrichment analysis revealed that differential tsRNAs indirectly participated in MAPK, AMPK, insulin resistance, the TNF signaling pathway, adipocytokine signaling pathway, and other signaling pathways by interacting with target genes. These are involved in bioenergetic metabolic regulatory processes, suggesting that tsRNAs may influence these pathways to mediate the regulation of energy metabolism in porcine adipocytes to promote lipid deposition, thus contributing to obesity. Our findings suggest a potential function of tsRNA in regulating obesity development.

Epigenetics and Gut Microbiota Crosstalk: A potential Factor in Pathogenesis of Cardiovascular Disorders.

Cardiovascular diseases (CVD) are the leading cause of mortality, morbidity, and "sudden death" globally. Environmental and lifestyle factors play important roles in CVD susceptibility, but the link between environmental factors and genetics is not fully established. Epigenetic influence during CVDs is becoming more evident as its direct involvement has been reported. The discovery of epigenetic mechanisms, such as DNA methylation and histone modification, suggested that external factors could alter gene expression to modulate human health. These external factors also influence our gut microbiota (GM), which participates in multiple metabolic processes in our body. Evidence suggests a high association of GM with CVDs. Although the exact mechanism remains unclear, the influence of GM over the epigenetic mechanisms could be one potential pathway in CVD etiology. Both epigenetics and GM are dynamic processes and vary with age and environment. Changes in the composition of GM have been found to underlie the pathogenesis of metabolic diseases via modulating epigenetic changes in the form of DNA methylation, histone modifications, and regulation of non-coding RNAs. Several metabolites produced by the GM, including short-chain fatty acids, folates, biotin, and trimethylamine-N-oxide, have the potential to regulate epigenetics, apart from playing a vital role in normal physiological processes. The role of GM and epigenetics in CVDs are promising areas of research, and important insights in the field of early diagnosis and therapeutic approaches might appear soon.

Genome-wide association study analysis to resolve the key regulatory mechanism of biomineralization in Pinctada fucata martensii.

Biomineralization-controlled exo-/endoskeleton growth contributes to body growth and body size diversity. Molluscan shells undergo ectopic biomineralization to form the exoskeleton and biocalcified "pearl" involved in invading defence. Notably, exo-/endoskeletons have a common ancestral origin, but their regulation and body growth are largely unknown. This study employed the pearl oyster, Pinctada fucata marntensii, a widely used experimental model for biomineralization in invertebrates, to perform whole-genome resequencing of 878 individuals from wild and breeding populations. This study characterized the genetic architecture of biomineralization-controlled growth and ectopic biomineralization. The insulin-like growth factor (IGF) endocrine signal interacted with ancient single-copy transcription factors to form the regulatory network. Moreover, the "cross-phylum" regulation of key long noncoding RNA (lncRNA) in bivalves and mammals indicated the conserved genetic and epigenetic regulation in exo-/endoskeleton growth. Thyroid hormone signal and apoptosis regulation in pearl oysters affected ectopic biomineralization in pearl oyster. These findings provide insights into the mechanism underlying the evolution and regulation of biomineralization in exo-/endoskeleton animals and ectopic biomineralization.

Divergent Carry-Over Effects of Hypoxia during the Early Development of Abalone

After being exposed to environmental stimuli during early developmental stages, some organisms may gain or weaken physiological regulating abilities, which would have long-lasting effects on their performance. Environmental hypoxia events can have significant effects on marine organisms, but for breeding programs and other practical applications, it is important to further explore the long-term physiological effects of early hypoxia exposure in economically significant species. In this study, the Pacific abalone Haliotis discus hannai was exposed to moderate hypoxia (∼4 mg/L) from zygote to trochophora, and the assessments of hypoxia tolerance were conducted on the grow-out stage. The results revealed that juvenile abalones exposed to hypoxia at the early development stages were more hypoxia-tolerant but with slower weight growth, a phenomenon called the trade-off between growth and survival. These phenotypic effects driven by the hypoxia exposure were explained by strong selection of genes involved in signal transduction, autophagy, apoptosis, and hormone regulation. Moreover, long non-coding RNA regulation plays an important role modulating carry-over effects by controlling DNA replication and repair, signal transduction, myocardial activity, and hormone regulation. This study revealed that the ability to create favorable phenotypic differentiation through genetic selection and/or epigenetic regulation is important for the survival and development of aquatic animals in the face of rapidly changing environmental conditions.

From molecular basics to agronomic benefits: Insights into noncoding RNA-mediated gene regulation in plants.

The development of plants is largely dependent on their growth environment. To better adapt to a particular habitat, plants have evolved various subtle regulatory mechanisms for altering gene expression. Noncoding RNAs (ncRNAs) constitute a major portion of the transcriptomes of eukaryotes. Various ncRNAs have been recognized as important regulators of the expression of genes involved in essential biological processes throughout the whole life cycles of plants. In this review, we summarize the current understanding of the biogenesis and contributions of small nucleolar RNA (snoRNA)- and regulatory long noncoding RNA (lncRNA)-mediated gene regulation in plant development and environmental responses. Many regulatory ncRNAs appear to be associated with increased yield, quality and disease resistance of various species and cultivars. These ncRNAs may potentially be used as genetic resources for improving agronomic traits and for molecular breeding. The challenges in understanding plant ncRNA biology and the possibilities to make better use of these valuable gene resources in the future are discussed in this review. This article is protected by copyright. All rights reserved.

5′-tRF-GlyGCC promotes breast cancer metastasis by increasing fat mass and obesity-associated protein demethylase activity

tRNA-derived fragments (tRFs) are a class of regulatory non-coding RNAs that play essential biological functions in cancer and stress-induced diseases. Several lines of evidence suggest that 5′-tRF-GlyGCC participates in tumor progression; however, its molecular mechanisms remain unclear. In this study, we explored the function of 5′-tRF-GlyGCC in breast cancer (BC) progression and studied the related potential molecular mechanisms. 5′-tRF-GlyGCC expression increased in human BC, and it promoted the proliferation, migration, and invasion of BC cells in vitro and tumor growth and metastasis in vivo. 5′-tRF-GlyGCC was found for the first time to bind directly to fat mass and obesity-associated proteins, and increase the activity of FTO demethylase, reducing eIF4G1 methylation, inhibiting autophagy, and promoting BC proliferation and metastasis. These findings suggest that 5′-tRF-GlyGCC might be a therapeutic target for treating BC.