Molecular Mechanisms of lncRNAs in the Dependent Regulation of Cancer and Their Potential Therapeutic Use

Deep whole genome and transcriptome sequencing have highlighted the importance of an emerging class of non-coding RNA longer than 200 nucleotides (i.e., long non-coding RNAs (lncRNAs)) that are involved in multiple cellular processes such as cell differentiation, embryonic development, and tissue homeostasis. Cancer is a prime example derived from a loss of homeostasis, primarily caused by genetic alterations both in the genomic and epigenetic landscape, which results in deregulation of the gene networks. Deregulation of the expression of many lncRNAs in samples, tissues or patients has been pointed out as a molecular regulator in carcinogenesis, with them acting as oncogenes or tumor suppressor genes. Herein, we summarize the distinct molecular regulatory mechanisms described in literature in which lncRNAs modulate carcinogenesis, emphasizing epigenetic and genetic alterations in particular. Furthermore, we also reviewed the current strategies used to block lncRNA oncogenic functions and their usefulness as potential therapeutic targets in several carcinomas.

Differentially Expressed Genes Related to Flowering Transition between Once- and Continuous-Flowering Roses

Roses are the most important cut flower crops and widely used woody ornamental plants in gardens throughout the world, and they are model plants for studying the continuous-flowering trait of woody plants. To analyze the molecular regulation mechanism of continuous flowering, comparative transcriptome data of once- and continuous-flowering roses in our previous study were used to conduct weighted gene co-expression network analysis (WGCNA) to obtain the candidate genes related to flowering transitions. The expression patterns of candidate genes at different developmental stages between Rosa chinensis “Old Blush” (continuous-flowering cultivar) and R. “Huan Die” (once-flowering cultivar) were investigated, and the relationship of the key gene with the endogenous hormone was analyzed. The results showed that the expression trends of VIN3-LIKE 1 (VIL1), FRIGIDA- LIKE 3 (FRI3), APETALA 2- LIKE (AP2-like) and CONSTANS-LIKE 2 (CO-like 2) genes were significantly different between “Old Blush” and “Huan Die”, and the expression trends of SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1) and CO-like 2 were consistent in the flowering transition of “Old Blush” under different environments. The changes in cytokinin and gibberellic acid (GA3) content were different in the two rose cultivars. The overall change trend of the abscisic acid and GA3 in the flowering transition of “Old Blush” under different environments was consistent. The promoter sequence of CO-like 2 contained a P-box element associated with gibberellin response, as well as binding sites for transcription factors. In a word, we found CO-like 2 associated with continuous flowering and some factors that may synergistically regulate continuous flowering. The results provided a reference for elucidating the molecular regulatory mechanisms of continuous-flowering traits in roses.

Tumor-Related Molecular Regulatory Mechanisms of Long Non-Coding RNA RMST: Recent Evidence

Background: Long non-coding RNA rhabdomyosarcoma 2-associated transcript (LncRNA RMST) will affect every aspect of tumor progression, such as proliferation, translocation and apoptosis. As a result, RMST can be used as an attractive biomarker for early diagnosis and clinical therapies of different disease states. This article aims to review pathophysiological functions, molecular mechanisms as well as promising biotherapies of RMST in multiple tumors. Methods: Through the systematic induction and summary of 46 papers published in PubMed concerning this study, the molecular mechanisms of RMST in all kinds of tumors have been reviewed. Results: LncRNA RMST is a tumor-related regulatory mediator, aberrantly expressed in diverse tumors, regarding medullary thyroid cancer, hepatocellular carcinoma, endometrial carcinoma, colon cancer, pancreatic cancer, glioma, Wilm’s tumor and breast cancer. Furthermore, as a mechanism-based player, RMST probably guides the translation and post-translation modification, containing DNA methylation and SUMOylation. It is capable of regulating distinct tumor cells and stem cells of biological behaviors via various molecular pathways. Conclusion: LncRNA RMST, potentially as an original therapeutic target, is valuable in the occurrence, development and apoptosis of different tumors.

Molecular Resiliency and Aging

Resilience is described as the ability to respond to acute forms of stress and recover to normal homeostasis. There is growing evidence that biology of resilience is entwined with the biology of aging. With increasing age, resilience decreases and is a likely contributor to increased morbidity, frailty and susceptibility to death with age. Conversely, increased resilience across numerous physiological markers of function is associated with longevity and healthy aging. The variation in resilience in populations suggests biological and molecular regulatory mechanisms that might provide insight into interventions to improve resilience, healthy aging and longevity. In this session, speakers will provide insight regarding short-term assays of resilience in animal models that prove useful both in delineating these biological mechanisms as well as inform on potential translational models to better understand biological resilience in human populations. The sessions focus is on defining these assays and discussion of the biological relevance each resilience assay in terms of the regulation of aging. The goals of these studies range from identifying potential predictors of individual lifespan within markers of functional resilience to leveraging geroscience to define whether markers of resilience can be modified through interventions to the aging process. Moreover, better understanding of the biology of resilience could assist in defining novel interventions that improve resilience and thereby enhance longevity.

Elastin Structure, Synthesis, Regulatory Mechanism and Relationship With Cardiovascular Diseases

As the primary component of elastic fibers, elastin plays an important role in maintaining the elasticity and tensile ability of cardiovascular, pulmonary and many other tissues and organs. Studies have shown that elastin expression is regulated by a variety of molecules that have positive and negative regulatory effects. However, the specific mechanism is unclear. Moreover, elastin is reportedly involved in the development and progression of many cardiovascular diseases through changes in its expression and structural modifications once deposited in the extracellular matrix. This review article summarizes the role of elastin in myocardial ischemia-reperfusion, atherosclerosis, and atrial fibrillation, with emphasis on the potential molecular regulatory mechanisms.

Comprehensive Analysis of REST/NRSF Gene in Glioma and Its ceRNA Network Identification

We sought to clarify the clinical relationship between REST/NRSF expression and the prognosis of glioma and explore the REST-associated competitive endogenous RNA (ceRNA) network in glioma. We downloaded RNA-seq, miRNA-seq and correlated clinical data of 670 glioma patients from The Cancer Genome Atlas and analyzed the correlation between REST expression, clinical characteristics and prognosis. Differentially expressed genes (DEGs) were identified with DESeq2 and analyzed with Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) using the Profiler package. Starbase was used to explore the regulatory interaction between REST and miRNAs or LncRNAs. The lncRNA-miRNA-REST ceRNA network was constructed with Cytoscape. RT-qPCR, WB, CCK8, wound-healing, and luciferase assays were performed to validate the ceRNA network. Results showed that REST expression was significantly higher in glioma patients than normal samples. Higher REST expression was significantly associated with worse overall survival, progression-free interval, and worse disease-specific survival in glioma patients. The DEGs of mRNA, miRNA, and lncRNA were identified, and GO and KEGG enrichment analyses were performed. Finally, REST-associated ceRNA networks, including NR2F2-AS1-miR129-REST and HOTAIRM1-miR137-REST, were experimentally validated. Thus, REST may be a prognostic biomarker and therapeutic target in glioma, and its regulatory network validated in this study may provide insights into glioma's molecular regulatory mechanisms.

Regulatory network of miRNA, lncRNA, transcription factor and target immune response genes in bovine mastitis

Pre- and post-transcriptional modifications of gene expression are emerging as foci of disease studies, with some studies revealing the importance of non-coding transcripts, like long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). We hypothesize that transcription factors (TFs), lncRNAs and miRNAs modulate immune response in bovine mastitis and could potentially serve as disease biomarkers and/or drug targets. With computational analyses, we identified candidate genes potentially regulated by miRNAs and lncRNAs base pair complementation and thermodynamic stability of binding regions. Remarkably, we found six miRNAs, two being bta-miR-223 and bta-miR-24-3p, to bind to several targets. LncRNAs NONBTAT027932.1 and XR_003029725.1, were identified to target several genes. Functional and pathway analyses revealed lipopolysaccharide-mediated signaling pathway, regulation of chemokine (C-X-C motif) ligand 2 production and regulation of IL-23 production among others. The overarching interactome deserves further in vitro/in vivo explication for specific molecular regulatory mechanisms during bovine mastitis immune response and could lay the foundation for development of disease markers and therapeutic intervention.

Overexpression of OsLCT2, a Low-Affinity Cation Transporter Gene, Reduces Cadmium Accumulation in Shoots and Grains of Rice

Cadmium (Cd)-contaminated rice is a serious issue affecting food safety. Understanding the molecular regulatory mechanisms of Cd accumulation in rice grains is crucial to minimizing Cd concentrations in grains. We identified a member of the low-affinity cation transporter family, OsLCT2 in rice. It was a membrane protein. OsLCT2 was expressed in all tissues of the elongation and maturation zones in roots, with the strongest expression in pericycle and stele cells adjacent to the xylem. When grown in Cd-contaminated paddy soils, rice plants overexpressing OsLCT2 significantly reduced Cd concentrations in the straw and grains. Hydroponic experiment demonstrated its overexpression decreased the rate of Cd translocation from roots to shoots, and reduced Cd concentrations in xylem sap and in shoots of rice. Moreover, its overexpression increased Zn concentrations in roots by up-regulating the expression of OsZIP9, a gene responsible for Zn uptake. Overexpression of OsLCT2 reduces Cd accumulation in rice shoots and grains by limiting the amounts of Cd loaded into the xylem and restricting Cd translocation from roots to shoots of rice. Thus, OsLCT2 is a promising genetic resource to be engineered to reduce Cd accumulation in rice grains.

Leaf Morphogenesis: Insights From the Moss Physcomitrium patens

Specialized photosynthetic organs have appeared several times independently during the evolution of land plants. Phyllids, the leaf-like organs of bryophytes such as mosses or leafy liverworts, display a simple morphology, with a small number of cells and cell types and lack typical vascular tissue which contrasts greatly with flowering plants. Despite this, the leaf structures of these two plant types share many morphological characteristics. In this review, we summarize the current understanding of leaf morphogenesis in the model moss Physcomitrium patens, focusing on the underlying cellular patterns and molecular regulatory mechanisms. We discuss this knowledge in an evolutionary context and identify parallels between moss and flowering plant leaf development. Finally, we propose potential research directions that may help to answer fundamental questions in plant development using moss leaves as a model system.

Identification of Quantitative Trait Loci Controlling the Development of Prickles in Eggplant by Genome Re-sequencing Analysis

Eggplant (Solanum melongena L.) is the third most important crop in the family of Solanaceae. Prickles are considered as the undesirable traits during the plantation of eggplant and the transportation of fruits. In this study, we constructed a high-quality genetic linkage Bin map derived from the re-sequencing analysis on a cross of a prickly wild landrace, 17C01, and a cultivated variety, 17C02. The major quantitative trait locus (QTL) controlling the development of prickles on the calyx (explained 30.42% of the phenotypic variation), named as qPC.12, was identified on a ~7 kb region on chromosome 12. A gene within qPC.12, which encodes a WUSCHEL-related homeobox-like protein, with higher expression levels in 17C01 calyx and 22-bp deletion in 17C02 was probably the functional gene for prickle formation. Results from this study would ultimately facilitate uncovering the molecular regulatory mechanisms underlying the development of a prickle in eggplant.