Circular RNAs:implications of signaling pathways and bioinformatics in human cancer

Circular RNAs(circRNAs)form a class of endogenous single-stranded RNA transcripts that are widely expressed in eukaryotic cells.These RNAs mediate post-transcriptional control of gene expression and have multiple functions in biological processes,such as transcriptional regulation and splicing.They serve predominantly as microRNA sponges,RNA-binding proteins,and templates for translation.More importantly,circRNAs are involved in cancer progression,and may serve as promising biomarkers for tumor diagnosis and therapy.Although traditional experimental methods are usually time-consuming and laborious,substantial progress has been made in exploring potential circRNA-disease associations by using computational models,summarized signaling pathway data,and other databases.Here,we review the biological characteristics and functions of circRNAs,including their roles in cancer.Specifically,we focus on the signaling pathways associated with carcinogenesis,and the status of circRNA-associated bioinformatics databases.Finally,we explore the potential roles of circRNAs as prognostic biomarkers in cancer.

1996—1999年2岁以下儿童对国家免疫指导方针的依从性

for at health maintenance organizations (HMOs) and to examine effects on immunization status. Methods. A cohort study of 176 134 children born between January 1,1994,and December 31,1997,and monitored from birth to the second birthday was performed. Subjects belonged to the Vaccine Safety Datalink Project,a study of children enrolled in 1 of 4 HMOs. Children were continuously enrolled in a HMO for the first 2 years of life. Prevailing recommendations regarding optimal ages of immunization and intervals between doses were applied to define appropriate immunization timing and immunization status. Noncompliance was defined as having a missing or late immunization or an immunization error. Immunization errors included invalid immunizations (too early to be acceptable),extra immunizations (superfluous immunizations or make-up immunizations for invalid immunizations),and missed opportunities resulting in late or missing immunizations. Results. Although 75.4% of children in these HMOs were up to date for all immunizations at 2 years,only 35.6% of children were fully compliant with recommended immunization practices. Less than 8% of children received all immunizations in accordance with strict interpretation of recommended guidelines. Fifty-one percent of children had at least 1 immunization error by age 2 years; 29.7% had a missed opportunity with subsequent late or missing immunization,20.4% had an invalid immunization,and 11.6% had an extra immunization. Common reasons for noncompliance included missed opportunities for the fourth Haemophilus influenzae type b vaccine (14.6% ) ,invalid fourth diphtheria-tetanus-pertussis/ acellular pertussis immunizations (11.0% ),and superfluous polio immunizations (9.8% ). Conclusions. Approximately 35.6% of children were compliant with prevailing childhood immunization recommendations from 1996 to 1999. Efforts to improve compliance with guidelines are recommended,to optimize childhood infectious disease prevention.

Dominance of transposable element‑related satDNAs results in great complexity of“satDNA library”and invokes the extension towards“repetitive DNA library”

Research on bivalves is fast-growing,including genome-wide analyses and genome sequencing.Several characteristics qualify oysters as a valuable model to explore repetitive DNA sequences and their genome organization.Here we char-acterize the satellitomes of five species in the family Ostreidae(Crassostrea angulata,C.virginica,C.hongkongensis,C.ariakensis,Ostrea edulis),revealing a substantial number of satellite DNAs(satDNAs)per genome(ranging between 33 and 61)and peculiarities in the composition of their satellitomes.Numerous satDNAs were either associated to or derived from transposable elements,displaying a scarcity of transposable element-unrelated satDNAs in these genomes.Due to the non-conventional satellitome constitution and dominance of Helitron-associated satDNAs,comparative satellitomics demanded more in-depth analyses than standardly employed.Comparative analyses(including C.gigas,the first bivalve species with a defined satellitome)revealed that 13 satDNAs occur in all six oyster genomes,with Cg170/HindIII satDNA being the most abundant in all of them.Evaluating the“satDNA library model”highlighted the necessity to adjust this term when studying tandem repeat evolution in organisms with such satellitomes.When repetitive sequences with potential variation in the organizational form and repeat-type affiliation are examined across related species,the introduction of the terms“TE library”and“repetitive DNA library”becomes essential.

Regulation and dysregulation of hair regeneration: aiming for clinical application

Hair growth and regeneration represents a remarkable example of stem cell function.Recent progress emphasizes the micro-and macro-environment that controls the regeneration process.There is a shift from a stem cell-centered view toward the various layers of regulatory mechanisms that control hair regeneration,which include local growth factors,immune and neuroendocrine signals,and dietary and environmental factors.This is better suited for clinical applica-tion in multiple forms of hair disorders:in male pattern hair loss,the stem cells are largely preserved,but androgen signaling diminishes hair growth;in alopecia areata,an immune attack is targeted toward the growing hair follicle without abrogating its regeneration capability.Genome-wide association studies further revealed the genetic bases of these disorders,although the precise pathological mechanisms of the identified loci remain largely unknown.By analyzing the dysregulation of hair regeneration under pathological conditions,we can better address the complex interactions among stem cells,the differentiated progeny,and mesenchymal components,and highlight the critical role of macroenvironment adjustment that is essential for hair growth and regeneration.The poly-genetic origin of these disorders makes the study of hair regeneration an interesting and challenging field.

Identification of Key Genes as Potential Drug Targets for Gastric Cancer

Gastric cancer(GC)is one of the most common cancers and ranks the third in cancer mortality all over the world.The goal of this study was to identify potential hub-genes,highlighting their functions,signaling pathways,and candidate drugs for the treatment of GC patients.We used publicly available next generation sequencing(NGS)data to identify differentially expressed(DE)genes.The top DE genes were mapped to STRING database to construct the protein-protein interaction(PPI)network and top hub genes were selected for further analysis.We found a total of 1555 DE genes with 870 upregulated and 685 downregulated genes in GC.We selected the top 400(200 upregulated and 200 downregulated)genes to construct a PPI network and extracted the top 15 hub genes.The gene ontology(GO)term and kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analyses of the 15 hub genes exposed some important functions and signaling pathways that were significantly associated with GC patients.The survival analysis of the hub genes disclosed that the lower expressions of the three hub genes CDH2,COL4A1,and COL5A2 were associated with better survival of GC patients.These three genes might be the candidate biomarkers for the diagnosis and treatment of GC.Then,we considered 3 key proteins(genomic biomarkers)(COL4A1,CDH2,and CO5A2)as the drug target proteins(receptors),performed their docking analysis with the 102 meta-drug agents,and found Everolimus,Docetaxel,Lanreotide,Venetoclax,Temsirolimus,and Nilotinib as the top ranked 6 candidate drugs with respect to our proposed target proteins for the treatment against GC patients.Therefore,the proposed drugs might play vital role for the treatment against GC patients.

Chemotherapy suppresses SHH gene expression via a specific enhancer

Sonic hedgehog(SHH)signaling is a key regulator of embryonic development and tissue homeostasis that is involved in gastrointestinal(GI)cancer progression.Regulation of SHH gene expression is a paradigm of long-range enhancer function.Using the classical chemotherapy drug 5-fluorouracil(5FU)as an example,here we show that SHH gene expression is suppressed by chemotherapy.SHH is downstream of immediate early genes(IEGs),including Early growth response 1(Egr1).A specific 139 kb upstream enhancer is responsible for its down-regulation.Knocking down EGR1 expression or blocking its binding to this enhancer renders SHH unresponsive to chemotherapy.We further demonstrate that down-regulation of SHH expression does not depend on 5FU’s impact on nucleotide metabolism or DNA damage;rather,a sustained oxidative stress response mediates this rapid suppression.This enhancer is present in a wide range of tumors and normal tissues,thus providing a target for cancer chemotherapy and its adverse effects on normal tissues.We propose that SHH is a stress-responsive gene downstream of IEGs,and that traditional chemotherapy targets a specific enhancer to suppress its expression.

Gene expression changes in blood RNA after swimming in a chlorinated pool

Exposure to disinfection by-products（DBP） such as trihalomethanes（THM） in swimming pools has been linked to adverse health effects in humans, but their biological mechanisms are unclear. We evaluated short-term changes in blood gene expression of adult recreational swimmers after swimming in a chlorinated pool. Volunteers swam 40 min in an indoor chlorinated pool. Blood samples were drawn and four THM（chloroform,bromodichloromethane, dibromochloromethane and bromoform） were measured in exhaled breath before and after swimming. Intensity of physical activity was measured as metabolic equivalents（METs）. Gene expression in whole blood m RNA was evaluated using Illumina Human HT-12v3 Expression-Bead Chip. Linear mixed models were used to evaluate the relationship between gene expression changes and THM exposure. Thirty-seven before-after pairs were analyzed. The median increase from baseline to after swimming were： 0.7 to 2.3 for MET, and 1.4 to 7.1 μg/m^3 for exhaled total THM（sum of the four THM）.Exhaled THM increased on average 0.94 μg/m^3 per 1 MET. While 1643 probes were differentially expressed post-exposure. Of them, 189 were also associated with exhaled levels of individual/total THM or MET after False Discovery Rate. The observed associations with the exhaled THM were low to moderate（Log-fold change range：-0.17 to 0.15）. In conclusion, we identified short-term gene expression changes associated with swimming in a pool that were minor in magnitude and their biological meaning was unspecific. The high collinearity between exhaled THM levels and intensity of physical activity precluded mutually adjusted models with both covariates. These exploratory results should be validated in future studies.