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@#Abstract: With the development of molecular biology, non-coding sRNA has been found to play an important regulatory role in gene expression and protein activity, affecting various biological pathways including mosquito resistance against insecticides. Understanding the molecular regulatory mechanisms of drug resistance is essential for controlling mosquitoes, , of which metabolic resistance being the most critical mechanism, mainly referring to the high expression of metabolic detoxification enzyme-related genes (especially the cytochrome P450 enzyme system) in mosquitoes. On the basis of verification of insecticide resistance-related genes, further research on the correlation between sRNA and mosquito resistance-related genes provides new ideas and directions for further exploring the mechanism of mosquito resistance. The study of mosquito metabolic resistance mechanism is of great significance for the control of vector mosquitoes, drug resistance monitoring and novel insecticide development. This article reviews the progress of research on the resistance genes, sRNAs biosynthesis, genes involved in regulating mosquito metabolic detoxification enzymes and their applications.
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Abstract RNAs that interact with PIWI (P-element Induced Wimpy) proteins, called piRNAs, were discovered in 2006. Considered the "guardians of the genome," piRNAs were first described in germ cells of Mus musculus and Drosophila melanogaster. Since then, studies have focused on elucidating their origin, biogenesis, and mechanisms of action. Today, we know some of the molecules that participate in these processes, but the nature of the molecular processes that they perform remains largely unknown. However, recent studies have demonstrated that both the piRNAs and their associated proteins are also expressed in somatic cells, suggesting that their scope of action is much greater than initially thought. In addition, their union to PIWI proteins generates a silencing complex that represses the transcriptional and post-transcriptional expression of repeated sequences, including elements known as "transposables". Finally, a recent discovery revealed that this complex could modulate the silencing of specific messenger RNAs (mRNA) necessary for cell regulation. The regulatory function that piRNAs perform in various cellular processes has led to a diversification in their study concerning various diseases, including cancer, where there are indications of their potential function as diagnostic tools, biomarkers for prognoses, and future therapeutic targets. Recently, changes in piRNAs expression have been observed in diseases related to air pollution exposition, such as respiratory diseases.
Resumen Los RNA que interactúan con las proteínas PIWI (P-element Induced Wimpy), conocidos como piRNA, fueron descubiertos en 2006. Desde entonces, los estudios se han enfocado en dilucidar su origen, biogénesis y mecanismos de acción. En la actualidad se conocen algunas de las moléculas que participan en estos procesos. Sin embargo, los procesos moleculares que estas llevan a cabo aún se desconocen. Considerados como los «guardianes del genoma¼, los piRNA inicialmente se describieron en células germinales de Mus musculus y Drosophila melanogaster, pero los estudios recientes han demostrado que tanto los piRNA como sus proteínas asociadas se expresan también en células somáticas, lo que sugiere que la acción de los piRNA es mayor de lo que antes se pensaba. Además, su unión con las proteínas PIWI genera un complejo de silenciamiento que reprime la expresión de manera transcripcional y postranscripcional de secuencias repetidas, Áincluyendo elementos conocidos como «transponibles¼. Por último, un descubrimiento ha demostrado que este complejo puede modular el silenciamiento de ciertos RNA mensajeros necesarios para la regulación celular. La función reguladora de los piRNA en múltiples procesos celulares ha contribuido a la diversificación de su estudio en diferentes enfermedades, incluyendo el cáncer, en el que hay indicaciones de su potencial función como herramientas de diagnóstico, biomarcadores de pronóstico y, en un futuro, dianas terapéuticas. Recientemente se han observado cambios en la expresión de piRNA en enfermedades relacionadas con la exposición a contaminantes ambientales, como las enfermedades respiratorias.
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BACKGROUND: Exosomes derived from mesenchymal stem cells can reduce myocardial ischemia and reperfusion injury, but there are some problems such as short half-life, fast clearance and low targeting. OBJECTIVE: To modify and encapsulate exosomes with temperature-sensitive chitosan hydrogel to increase the retention rate of exosomes in the body, and to achieve better therapeutic effect. METHODS: Cell transfection method was used to knock down piR823 in exosomes derived from umbilical cord mesenchymal stem cells, and the effect of knockdown of piR823 exosomes on the proliferation and apoptosis of C2C12 cells was detected. Chitosan/β-sodium glycerophosphate temperature-sensitive hydrogel was prepared and mixed directly with exosomes to prepare chitosan/β-sodium glycerophosphate temperature-sensitive hydrogel encapsulated with exosomes. The gel-forming properties, rheology and in vitro sustained release properties of the hydrogel after encapsulation of exosomes were tested. Thirty C57BL/6J mice were taken to establish hind limb ischemia models, and randomly divided into five groups. The gastrocnemius of group A was injected with PBS; group B was injected with chitosan/β-sodium glycerophosphate temperature-sensitive hydrogel; and group C was injected with exosomes-encapsulated chitosan/β-sodium glycerophosphate temperature-sensitive hydrogel; group D was injected with exosomes; group E was injected with exosomes knocking down piR823. Limb function and recovery, blood flow, grip strength, exercise endurance and muscle regeneration were detected in each group. RESULTS AND CONCLUSION: (1) Exosomes knocking down piR823 inhibited the proliferation of C2C12 cells; normal exosomes inhibited hydrogen peroxide-induced apoptosis of C2C12 cells. The inhibitory effect of exosomes on apoptosis was weakened after piR823 was knocked down. (2) The hydrogel encapsulating exosomes had gel-forming properties, but the gel-forming time was shortened, and it could slowly and continuously release exosomes for more than 30 days. (3) After 28 days of hindlimb ischemia, the blood flow recovery of the left limb in group C was better than that in groups B and D (P < 0.05); it in group D was better than group E (P < 0.05); the grip strength, endurance, running time and distance of group C were better than those of groups D and B (P < 0.05), and above indexes in group D were better than in group E (P < 0.05). Muscle regeneration was better in group C than in groups B and D (P < 0.05), and it in group D was better than group E (P < 0.05). (4) The results showed that encapsulation of exosomes by chitosan/β-sodium glycerophosphate temperature-sensitive hydrogel prolonged the residence time of exosomes in vivo, significantly enhanced blood perfusion and recovery of tissue function after ischemia, and the treatment effect was more significant.
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@#[摘 要] PIWI蛋白相互作用RNA（PIWI-interacting RNA，piRNA）及PIWI蛋白通过表观遗传沉默影响肿瘤的发生发展，并与 恶性肿瘤的增殖、侵袭、转移和预后不良密切相关，是潜在的新型肿瘤标志物和预后判断因子。卵巢癌是妇科三大恶性肿瘤之 一，晚期易复发转移、产生耐药和病死率高，目前仍缺乏有效的早期肿瘤标志物和诊断方法。近年有研究表明，piRNA和PIWI蛋 白在卵巢癌中呈异常表达，通过转录后机制参与调控卵巢癌的发生发展。本文主要从piRNA的生物学特性、在肿瘤中表观遗传 沉默的相关机制和piRNA在卵巢癌中的作用及其机制最新研究进展进行综述，为研究早期诊断卵巢癌的分子标志物提供参考 依据。
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The mammalian epididymis not only plays a fundamental role in the maturation of spermatozoa, but also provides protection against various stressors. The foremost among these is the threat posed by oxidative stress, which arises from an imbalance in reactive oxygen species and can elicit damage to cellular lipids, proteins, and nucleic acids. In mice, the risk of oxidative damage to spermatozoa is mitigated through the expression and secretion of glutathione peroxidase 5 (GPX5) as a major luminal scavenger in the proximal caput epididymidal segment. Accordingly, the loss of GPX5-mediated protection leads to impaired DNA integrity in the spermatozoa of aged Gpx5
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The incidence of male infertility is increasing year by year, but there is a lack of non-invasive accurate diagnostic indicators for this disease, and the pathogenesis of idiopathic infertility is not yet fully clarified. Recent studies have found that there are various small non-coding RNAs (sncRNA) in the human seminal plasma and spermatic exosomes, which can be used as a novel non-invasive biomarker of male infertility. This review outlines the latest research updates on the relationship between sncRNAs in the seminal plasma and male infertility, aiming to provide some new ideas for the screening of the molecular markers of male infertility and study of its underlying molecular mechanisms.
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Non-coding RNA (ncRNA), expressed widely in organisms and comprised of a complex, regulatory and controlling biologically network, is an emerging theme in the biomedicine field at present. Regulatory sncRNAs, for example, microRNA (miRNA), endogenous small interfering RNA (siRNA) and PIWI-interacting RNA (piRNA), are the key members of the gene regulatory network and play important roles in the regulation of multiple pathophysiological activities in cells. Male infertility, a serious social problem all over the world, is mainly related the malfunctions of the spermatogenesis caused by known or unknown factors; and finally result in azoospermia, oligozoospermia or asthenospermia. Recent research indicated that regulatory sncRNAs play important roles in the development, differentiation and mature of the germ cells and their functions at different stages by silencing the transposable elements and regulating the expression of coding gene; and their abnormal expression in germ cells at different stage is closely related to male infertility. In this review, the roles and recent progresses of regulatory sncRNA focusing on piRNA to provide insight for future research in this field and for the diagnoses, interventions and treatments of male infertility are briefly summarized.
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Objective@#To investigates the role of piwi-interacting RNAs (piRNA) in the occurrence and development of hepatocellular carcinoma.@*Methods@#Second-generation small RNA sequencing was performed on cancer and paracancerous tissues, metastatic and non-metastatic liver cancer tissues of patients with liver cancer, and the sequencing data were filtered out for the common RNA sequences to be repeated. The piRNA predictor was used to forecast the possible new piRNA merged with the downloaded known piRNA to screen out distinction. A miRanda algorithm was used to predict the corresponding target genes and functional enrichment analysis. piRNA was selected for experimental functional (migration) analysis. An independent t-test was used to compare means between the two groups.@*Results@#66 772 piRNAs (known 149) were obtained by sequencing. 241 piRNAs were found in cancer and paracancerous tissues, and 1 634 piRNAs were found in metastatic and non-metastatic tumors. Analysis of the GO and KEGG pathways of the target genes of differential piRNAs revealed that they were mainly involved in cell adhesion. An experimental functional analysis was performed on the selected Pirna (PIR1/97), which showed that it promoted the migration of hepatoma cells (LM3: t = 8.829, P < 0.05; PLC: t = 7.318, P < 0.05).@*Conclusion@#The expression levels of piRNA in hepatocellular carcinoma patients with cancer and paracancerous tissues, metastasis and non-metastatic liver cancer tissues are different and it could be entailed in the metastasis process of hepatocellular carcinoma. Hence, experimental functional analysis is required for research and experimental confirmation.
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Resumen Los piRNA son secuencias de 24 a 32 nucleótidos asociados a proteínas PIWI de la familia argonauta, la cual posee propiedad endonucleasa. Son sintetizados a partir de regiones intergénicas repetitivas y su principal función, es el silenciamiento de transposones, sin embargo, se ha encontrado que su descontrol está asociado con el desarrollo de diversos tipos de cáncer. Varios piRNAs han sido propuestos como biomarcadores del desarrollo tumoral, sin embargo, no en todos los tipos de cáncer han sido estudiados, siendo el cáncer de mama y el cáncer gástrico los que encabezan la lista con un mayor número de publicaciones. El presente trabajo, se centra en conocer los piRNAs de mayor relevancia en tipos específicos de cáncer con la finalidad de promover su análisis en casos de cáncer en los que han sido poco estudiados, o que predominan epidemiológicamente en ciertas poblaciones.
Abstract The piRNAs are sequences from 24 to 32 nucleotides associated with PIWI proteins from the Argonauta family, which possesses endonuclease holdings. They are synthesized from repetitive intergenic regions and their main function is the silencing of transposons, however, it has been found that its lack of control is associated with the development of various types of cancer. Several piRNAs have been associated as biomarkers of tumor development, however, It has not been studied in all types of cancer, recent investigations show that breast and gastric cancer are on top of the list with more publications related with piRNAs. Therefore, the present review focuses on knowing the most relevant piRNAs in specific types of cancer, in order to promote their analysis in the poorly studied cancer or that predominate epidemiologically in certain populations.
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Piwi-interacting RNAs (piRNAs) are a distinct class of small non-coding RNAs specifically expressed in the germline of many species. Studies show that the piRNA pathway influences spermatogenesis by translation regulation, germline stem cell maintenance, RNA degradation and gene defense in addition to inhibition of transposable elements. This review presents an overview of the piRNA pathway focusing on piRNA, PIWI protein and other related proteins and outlines the latest advances in the studies of the piRNA pathway in spermatogenesis.
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The presence of RNA has been confirmed in mature human sperm and plays an important role in altering the early events of embryos. Increasing evidence indicates that the expression of small non-coding RNAs can be changed by environmental exposures such as the structure of paternal diet and the status of stress. As the carriers of paternal information and epigenetic markers, small non-coding RNAs can alter the development of early embryos and offspring and mediate transgenerational transmission, which offers a new target for the studies of the epigenetics of sperm. Sperm piRNA, microRNA and tRNA, which are widely present in male germ cells, can mediate transgenerational transmission via related regulation mechanisms. This review introduces some new findings about the transgenerational epigenetics concerning the three small non-coding RNAs in sperm and offers a novel insight into male reproduction.
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piRNA(Piwi-interacting RNA) is a novel class of small single strand RNA that were recently isolated from testes of the mammals, associate with PIWI proteins, and are organized into distinct genomic clusters. These RNAs are typically 30 nt long, strikingly different from microRNAs in their length, expression pattern, and genomic organization. piRNA has a role in RNA silencing via the formation of an RNA-induced silencing complex (RISC) with Piwi proteins, these piRNA complexes (piRCs) have been linked to transcriptional gene silencing of retrotransposons and other genetic elements in germ line cells, particularly those in spermatogenesis.Recent researches and progresses of piRNAs are reviewed.
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piRNA is a novel class of small single strand RNA that were recently isolated from testes of the mammals. These RNAs are bigger (26～31 nt) than most previously described small RNAs (21～23 nt) and are associated with Piwi-subfamily members of the Argonaute protein family.