Type Of Small RNA Research Articles

MiR-30b-3p Inhibits the Proliferation and Invasion of Lung Adenocarcinoma by Targeting COX6B1

背景与目的肺腺癌（lung adenocarcinoma, LUAD）是当前最常见的肺癌亚型，微小RNA（microRNAs, miRNAs）是一类非编码小RNA，在细胞活动中发挥核心作用。miR-30b-3p在许多类型的癌症中均起到了关键作用，但关于其在肺腺癌中如何发挥作用的研究仍然很少。本研究通过探索miR-30b-3p在肺腺癌增殖和侵袭中的作用和机制，以期为临床上抑制肺腺癌的增殖和侵袭拓展新的方向。方法利用NCBI生物数据库查找肺腺癌中差异表达明显的miRNA，并查询其差异表达及生存曲线；采用实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction, qRT-PCR）检测miR-30b-3p在各肺腺癌细胞系中的表达；5-乙炔基-2’脱氧尿嘧啶核苷（5-ethynyl-2'-deoxyuridine, EdU）细胞增殖实验和Transwell实验检测各组A549细胞增殖和侵袭能力的变化；使用在线预测数据网站确定miR-30b-3p的靶蛋白；Western blot验证COX6B1在不同组肺腺癌细胞中的表达情况；双荧光素酶实验证实miR-30b-3p与COX6B1是否存在结合位点。结果miR-30b-3p在肺腺癌组织和细胞中表达下调（P<0.05），低表达水平的miR-30b-3p与肺腺癌患者的不良预后有关（P=0.005,8）；过表达miR-30b-3p能够抑制肺腺癌细胞的增殖与侵袭能力（P<0.05）；双荧光素酶实验证明miR-30b-3p和COX6B1存在结合位点（P<0.05）；Western blot实验表明在肺腺癌细胞A549中，过表达miR-30b-3p能够下调COX6B1的表达（P<0.05）；EdU细胞增殖实验和Transwell侵袭实验表明，miR-30b-3p的过表达能够逆转上调COX6B1对肺腺癌细胞增殖和侵袭能力的促进作用（P<0.05）。结论miR-30b-3p在肺腺癌中起到了抑癌基因的作用，并能够通过调控COX6B1的表达来抑制肺腺癌的增殖和侵袭。

Identification of Novel tRNA-Leu-CAA-Derived tsRNAs for the Diagnosis and Prognosis of Diffuse Gliomas.

PurposetsRNA is a type of small non-coding RNA derived from tRNA. Diffuse gliomas are the most common brain tumors. This investigation focused on tsRNA identification and characterization within gliomas.MethodsThe sequences of human tRNA and tsRNAs were taken from GtRNAdb, tRFdb and tRFexplorer databases. Data processing and bioinformatic analysis were performed with R or Python software. The expression of tsRNAs in glioma tissues was analyzed by qRT-PCR assay.ResultsWith computational approaches, we identified hundreds of tsRNAs with available expression abundance in the glioma datasets, most of them derived from the 3′ end or 5′ end of mature tRNA. Among the tsRNAs derived from tRNA-Leu-CAA, ts-26, tRFdb-3012a, and tRFdb-3012b (tRFdb-3012a/b) were significantly decreased in diffuse gliomas. The clinical survivals of glioma patients with low tsRNA (ts-26, tRFdb-3012a, and tRFdb-3012b) expression were remarkably worse than that of those with high expression. Expression of tRFdb-3012a/b was correlated with IDH mutant status and MGMT promoter mutation in gliomas, and tRFdb-3012a/b and ts-23 tended to be highly expressed in patients with the IDH mutant. The enrichment analysis showed that some tRFdb-3012a/b-related genes were enriched in RNA splicing and processing, the spliceosome pathway and astrocyte molecular signatures. Moreover, the 3′ untranslated region of the RBM43 gene was predicted to contain putative binding sites of tRFdb-3012a/b, ts-26 may directly bind to the 3′ untranslated region of the HOXA13 gene, and the expressions of both RBM43 and HOXA13 were up-regulated in diffuse gliomas. High RBM43 and HOXA13 expressions were significantly associated with poor survival outcome of glioma patients.ConclusionThese results suggest that tRNA-Leu-CAA-derived tsRNAs (ts-26, tRFdb-3012a, and tRFdb-3012b) could be explored as diagnostic and prognostic biomarkers for diffuse gliomas, and tRFdb-3012a/b and ts-26 may play an important role in the progression of gliomas, through binding RBM43 and HOXA13, respectively.

Box C/D snoRNA SNORD89 influences the occurrence and development of endometrial cancer through 2’-O-methylation modification of Bim

The small nucleolar RNA (snoRNA) is a type of small non-coding RNA widely distributed in the nucleoli of eukaryotic cells, promoting cancer development. The aim of this study was to assess box C/D snoRNA 89 (SNORD89) dysregulations in endometrial cancer. According to the TCGA database as well as the International Federation of Gynecology and Obstetrics (FIGO), higher SNORD89 expression is found in endometrial cancer tissues. In addition, the SNORD89 expression level was higher in endometrial carcinoma with lymph node metastasis than in endometrial carcinoma without lymph node metastasis. By interacting with the conservative chaperone protein methylase fibrillarin (Fbl), SNORD89 inhibits the translation process of the Bim gene, leading to a decrease in Bim protein. Cancer-promoting effect of SNORD89 can be reversed by Fbl knockdown or Bim overexpressing. What’s more, ASO-mediated silencing of SNORD89 could inhibit endometrial cancer cell proliferation and migration ability. Taken together, SNORD89 can modify Bim through 2′-O-methylation and affect downstream signaling pathways to promote endometrial cancer occurrence and development. The role of methylation modification in the prevention and treatment of endometrial cancer provides a new understanding and SNORD89 may be a new diagnostic and therapeutic target for endometrial cancer.

Efficient delivery of Echinococcus multilocularis miRNAs using chitosan nanoparticles.

Alveolar echinococcosis caused by Echinococcus multilocularis is an important zoonotic disease, a great threat to human health due to limited interventions. microRNAs are a type of small non-coding RNA that plays a key role in many diseases and is considered as a potential therapeutic target for control of parasitic diseases. However, naked miRNAs are difficult to enter into cells and are easily degraded in both external and internal environments. Chitosan (CS) has recently been used as a promising vehicle for delivery of nucleic acids. Therefore, we prepared miRNA-bearing CS nanoparticles and investigated the physicochemical properties as well as the delivery efficiency. We found that CS nanoparticles was relatively stable, offered miRNA strong protection from degradation and had low cytotoxicity with no significant effects on cell proliferation and apoptosis. CS nanoparticles were shown to be easily absorbed by cells and have remarkable liver tropism. Furthermore, CS nanoparticles were used to efficiently deliver E. multilocularis miR-4989 in vitro and in vivo and caused a significant reduction in the expression of UBE2N in the liver, a potential target of emu-miR-4989, at both mRNA and protein levels. Our data demonstrate that CS nanoparticles can act as a vehicle for efficient liver-targeted delivery of miRNAs and for development of miRNA-based therapeutics against E. multilocularis infection.

PiWi RNA in Neurodevelopment and Neurodegenerative Disorders.

The discovery of the mysterious dark matter of the genome expands our understanding of modern biology. Beyond the genome, the epigenome reveals a hitherto unknown path of key biological and functional gene control activities. Extraordinary character-P element wimpy testis-induced (PiWi)-interacting RNA (piRNA) is a type of small non-coding RNA that acts as a defender by silencing nucleic and structural invaders. PiWi proteins and piRNAs can be found in both reproductive and somatic cells, though germ line richness has been partially unravelled. The primary function is to suppress invading DNA sequences known as Transpose of Elements (TEs) that move within genomic DNA and downstream target genes via Transcriptional Gene Silencing (TGS) and Post-Translational Gene Silencing (PTGS). Germline piRNAs preserve genomic integrity, stability, sternness, and influence imprinting expression. The novel roles of somatic tissue-specific piRNAs have surprised researchers. In metazoans, including humans, piRNA regulates neurodevelopmental processes. The PiWi pathway regulates neural heterogeneity, neurogenesis, neural plasticity, and transgenerational inheritance of adaptive and long-term memory. Dysregulated piRNA causes neurodevelopmental, neurodegenerative, and psychiatric illness. A faulty piRNA signature results in inadvertent gene activation via TE activation, incorrect epigenetic tags on DNA, and/or histones. Imprinting expression is influenced by germline piRNAs, which maintain genomic integrity, stability, and sternness. New roles for piRNAs specific to somatic tissues have been discovered. Metazoans, including humans, are regulated by piRNA. In addition, the PiWi pathway regulates neuronal heterogeneity and neurogenesis as well as brain plasticity and transgenerational inheritance of adaptive and long-term memory. When piRNA is dysregulated, it can lead to neurodegenerative and psychiatric illnesses. Inappropriate gene activation or inactivation is caused by aberrant piRNA signatures, TE activation, inappropriate epigenetic marks on DNA, and/or histones. Defective piRNA regulation causes abnormal brain development and neurodegenerative aetiology, which promotes life-threatening disorders. Exemplification of exciting roles of piRNA is still in its early stages, so future research may expand on these observations using novel techniques and launch them as potential biomarkers for diagnostics and therapeutics. In this review, we summarised the potential gene molecular role of piRNAs in regulating neurobiology and serving as novel biomarkers and therapeutic targets for life-threatening disease.

MicroRNAs: Important Regulatory Molecules in Acute Lung Injury/Acute Respiratory Distress Syndrome.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is an overactivated inflammatory response caused by direct or indirect injuries that destroy lung parenchymal cells and dramatically reduce lung function. Although some research progress has been made in recent years, the pathogenesis of ALI/ARDS remains unclear due to its heterogeneity and etiology. MicroRNAs (miRNAs), a type of small noncoding RNA, play a vital role in various diseases. In ALI/ARDS, miRNAs can regulate inflammatory and immune responses by targeting specific molecules. Regulation of miRNA expression can reduce damage and promote the recovery of ALI/ARDS. Consequently, miRNAs are considered as potential diagnostic indicators and therapeutic targets of ALI/ARDS. Given that inflammation plays an important role in the pathogenesis of ALI/ARDS, we review the miRNAs involved in the inflammatory process of ALI/ARDS to provide new ideas for the pathogenesis, clinical diagnosis, and treatment of ALI/ARDS.

The Role and Mechanism of microRNA-1224 in Human Cancer.

microRNAs (miRNAs) are a type of small endogenous non-coding RNAs composed of 20-22 nucleotides, which can regulate the expression of a gene by targeting 3’ untranslated region (3’-UTR) of mRNA. Many studies have reported that miRNAs are involved in the occurrence and progression of human diseases, including malignant tumors. miR-1224 plays significant roles in different tumors, including tumor proliferation, metastasis, invasion, angiogenesis, biological metabolism, and drug resistance. Mostly, it serves as a tumor suppressor. With accumulating proofs of miR-1224, it can act as a potential bio-indicator in the diagnosis and prognosis of patients with cancer. In this article, we review the characteristics and research progress of miR-1224 and emphasize the regulation and function of miR-1224 in different cancer. Furthermore, we conclude the clinical implications of miR-1224. This review may provide new horizons for deeply understanding the role of miR-1224 as biomarkers and therapeutic targets in human cancer.

Selective sorting and secretion of hY4 RNA fragments into extracellular vesicles mediated by methylated YBX1 to promote lung cancer progression

BackgroundExtracellular vesicles (EVs) are emerging mediators of intercellular communication that have been shown to play important roles in tumor progression. YRNA fragments, a type of small non-coding RNA, are dysregulated in non-small cell lung cancer (NSCLC) cell-derived EVs, suggesting that they may be an effective biomarker for cancer diagnosis and treatment strategies.MethodsDifferentially expressed YRNA hY4 fragments (hY4F) in EVs from NSCLC cells and normal lung fibroblasts were isolated by differential ultra-centrifugation. RNA-binding proteins that interacted with hY4F were identified by screening with an RNA pulldown assay and mass spectrometry. The molecular mechanism of hY4F and the RNA-binding protein Y box binding protein 1 (YBX1) was demonstrated by qRT-PCR, western blot, RNA pulldown, and rescue experiments. Transcriptome sequencing, qRT-PCR validation, bioinformatics analysis and NF-κB pathway inhibitor assays elucidate the mechanism of YBX1 and hY4F inhibiting lung cancer. A peptide pulldown assay was performed to screen and identify a potential methyltransferase for YBX1. The roles of hY4F, YBX1, and SET domain containing 3 in biological functions, such as proliferation, migration, invasion, and apoptosis, in lung cancer cells were also examined by EdU incorporation assay, Transwell assay, flow cytometry, and other methods. Lastly, a mouse xenograft assay was used to assess the clinical relevance of YBX1 and hY4F in vivo.ResultsOur data demonstrate that hY4 RNA fragments were upregulated in lung cancer- derived EVs, hY4F inhibits tumor progression through downregulating MAPK/NF-κB signaling, and then the selective sorting and secretion of hY4F into lung cancer EVs is regulated by the RNA-binding protein YBX1. Furthermore, we identified lysine K264 within the YBX1 C-terminal domain as the necessary site for its interaction with hY4Fs. K264 is modified by methylation, which affects its binding to hY4F and subsequent selective sorting into EVs in lung cancer cells.ConclusionOur findings demonstrate that hY4F acts as a tumor suppressor and is selectively sorted into lung cancer cell-derived EVs by interacting with methylated YBX1, which in turn promotes lung cancer progression. hY4F is a promising circulating biomarker for non-small cell lung cancer diagnosis and prognosis and an exceptional candidate for further therapeutic exploration.

TiRNA-Val promotes angiogenesis via Sirt1\u2013Hif-1\u03b1 axis in mice with diabetic retinopathy

BackgroundDiabetic retinopathy (DR) is a specific microvascular complication arising from diabetes, and its pathogenesis is not completely understood. tRNA-derived stress-induced RNAs (tiRNAs), a new type of small noncoding RNA generated by specific cleavage of tRNAs, has become a promising target for several diseases. However, the regulatory function of tiRNAs in DR and its detailed mechanism remain unknown.ResultsHere, we analyzed the tiRNA profiles of normal and DR retinal tissues. The expression level of tiRNA-Val was significantly upregulated in DR retinal tissues. Consistently, tiRNA-Val was upregulated in human retinal microvascular endothelial cells (HRMECs) under high glucose conditions. The overexpression of tiRNA-Val enhanced cell proliferation and inhibited cell apoptosis in HRMECs, but the knockdown of tiRNA-Val decreased cell proliferation and promoted cell apoptosis. Mechanistically, tiRNA-Val, derived from mature tRNA-Val with Ang cleavage, decreased Sirt1 expression level by interacting with sirt1 3'UTR, leading to the accumulation of Hif-1α, a key target for DR. In addition, subretinal injection of adeno-associated virus to knock down tiRNA-Val in DR mice ameliorated the symptoms of DR.ConclusiontiRNA-Val enhance cell proliferation and inhibited cell apoptosis via Sirt1/Hif-1α pathway in HRMECs of DR retinal tissues.

MiRNAFinder: A comprehensive web resource for plant Pre-microRNA classification

microRNAs (miRNAs) are known as one of the small non-coding RNA molecules that control the expression of genes at the RNA level, while some operate at the DNA level. They typically range from 20 to 24 nucleotides in length and can be found in the plant and animal kingdoms as well as in some viruses. Computational approaches have overcome the limitations of the experimental methods and have performed well in identifying miRNAs. Compared to mature miRNAs, precursor miRNAs (pre-miRNAs) are long and have a hairpin loop structure with structural features. Therefore, most in-silico tools are implemented for pre-miRNA identification. This study presents a multilayer perceptron (MLP) based classifier implemented using 180 features under sequential, structural, and thermodynamic feature categories for plant pre-miRNA identification. This classifier has a 92% accuracy, a 94% specificity, and a 90% sensitivity. We have further tested this model with other small non-coding RNA types and obtained 78% accuracy. Furthermore, we introduce a novel dataset to train and test machine learning models, addressing the overlapping data issue in the positive training and testing datasets presented in PlantMiRNAPred for the classification of real and pseudo-plant pre-miRNAs. The new dataset and the classifier that can be used with any plant species are deployed on a web server freely accessible at http://mirnafinder.shyaman.me/.

MicroRNA and Exosome in Retinal-related Diseases: Their Roles in the Pathogenesis and Diagnosis.

The precise and exquisite architecture of the retina is directly related to vision. Therefore, any mechanisms associated with disruption of retinal structure could affect the quality of vision. A large number of studies indicated that several cellular and molecular processes are involved in retina pathogenesis. Among different risk factors reported as important players in retina diseases, deregulation of epigenetic contributors has critical roles in the pathogenesis of these diseases. MicroRNAs (miRNAs) are a type of small non-coding RNAs that are involved in various signaling pathways involved in retina diseases. These molecules exert their function by targeting a sequence of cellular and molecular signals. Long-non coding RNAs (lncRNAs) and circular RNAs are other non-coding RNAs, which can exert their regulatory roles via miRNA sponging. In this regard, it has been showed that miRNA sponging could modulate a variety of pathways in retinal diseases. Besides miRNAs, exosomes are other players in the pathogenesis of retinal diseases. Exosomes are biological vectors that could carry their cargos to recipient cells. The cargos of exosomes (i.e., proteins, lncRNAs, miRNAs, and fragments of DNA) change behaviors of host cells. Here, we summarized the roles of miRNAs, miRNAs sponging and exosomes in the pathogenesis of retinal diseases.

PIWI-Interacting RNAs (piRNAs): Promising Applications as Emerging Biomarkers for Digestive System Cancer.

PIWI-interacting RNAs (piRNAs) are a novel type of small non-coding RNAs (sncRNAs), which are 26–31 nucleotides in length and bind to PIWI proteins. Although piRNAs were originally discovered in germline cells and are thought to be essential regulators for germline preservation, they can also influence gene expression in somatic cells. An increasing amount of data has shown that the dysregulation of piRNAs can both promote and repress the emergence and progression of human cancers through DNA methylation, transcriptional silencing, mRNA turnover, and translational control. Digestive cancers are currently a major cause of cancer deaths worldwide. piRNAs control the expression of essential genes and pathways associated with digestive cancer progression and have been reported as possible biomarkers for the diagnosis and treatment of digestive cancer. Here, we highlight recent advances in understanding the involvement of piRNAs, as well as potential diagnostic and therapeutic applications of piRNAs in various digestive cancers.

Differential expression profiles and function prediction of tRNA-derived fragments in fibrous dysplasia

ObjectiveFibrous dysplasia (FD) is a bone disease featuring that normal bone matrix is replaced by fibrous tissue and immature bone tissue. Transfer RNA-derived RNA fragments (tRFs) and tRNA halves (tiRNAs) are types of small non-coding RNA that produced by specific shearing of mature tRNA. Here, we conducted a comparative analysis of the expression of tRFs/tiRNAs in BMSCs and FD BMSCs. DesignsThe differential expression of tRFs/tiRNAs was detected by high-throughput sequencing technique, and validated by qRT-PCR. Bioinformatics analyses including prediction of target genes, gene ontology (GO) enrichment and KEGG pathway analysis and protein-protein interaction (PPI) network analysis were performed. ResultsThe results detected 1 significantly upregulated tDR (tRNA-derived small RNA) and 3 downregulated tDRs in FD BMSCs. Predictions of target genes, GO and KEGG pathway analysis indicated that these tRFs were mainly involved in regulation of immune response, osteoclast differentiation, calcium ion transport, apoptotic signaling pathway, cell proliferation and endocrine system development. The PPI network analysis showed that PPP2R5A, ADAMTS1, PPARA, and POLR2C were the most frequently interacted proteins in target genes. ConclusionsOur findings provided a comprehensive analysis of the expression of tRFs/tiRNAs in FD BMSCs and BMSCs, and they could serve as potential therapeutic targets.

Mammalian antiviral systems directed by small RNA.

There are strong incentives for human populations to develop antiviral systems. Similarly, genomes that encode antiviral systems have had strong selective advantages. Protein-guided immune systems, which have been well studied in mammals, are necessary for survival in our virus-laden environments. Small RNA–directed antiviral immune systems suppress invasion of cells by non-self genetic material via complementary base pairing with target sequences. These RNA silencing-dependent systems operate in diverse organisms. In mammals, there is strong evidence that microRNAs (miRNAs) regulate endogenous genes important for antiviral immunity, and emerging evidence that virus-derived nucleic acids can be directly targeted by small interfering RNAs (siRNAs), PIWI-interacting RNAs (piRNAs), and transfer RNAs (tRNAs) for protection in some contexts. In this review, we summarize current knowledge of the antiviral functions of each of these small RNA types and consider their conceptual and mechanistic overlap with innate and adaptive protein-guided immunity, including mammalian antiviral cytokines, as well as the prokaryotic RNA-guided immune system, CRISPR. In light of recent successes in delivery of RNA for antiviral purposes, most notably for vaccination, we discuss the potential for development of small noncoding RNA–directed antiviral therapeutics and prophylactics.

PiRBase: integrating piRNA annotation in all aspects

Piwi-interacting RNAs are a type of small noncoding RNA that have various functions. piRBase is a manually curated resource focused on assisting piRNA functional analysis. piRBase release v3.0 is committed to providing more comprehensive piRNA related information. The latest release covers >181 million unique piRNA sequences, including 440 datasets from 44 species. More disease-related piRNAs and piRNA targets have been collected and displayed. The regulatory relationships between piRNAs and targets have been visualized. In addition to the reuse and expansion of the content in the previous version, the latest version has additional new content, including gold standard piRNA sets, piRNA clusters, piRNA variants, splicing-junction piRNAs, and piRNA expression data. In addition, the entire web interface has been redesigned to provide a better experience for users. piRBase release v3.0 is free to access, browse, search, and download at http://bigdata.ibp.ac.cn/piRBase.

HnRNPA2B1-Mediated Extracellular Vesicles Sorting of miR-122-5p Potentially Promotes Lung Cancer Progression.

Extracellular vesicles (EVs) released by tumor cells play important roles on the remodeling of the tumor–stromal environment and on promoting tumor metastasis. Our earlier studies revealed that miR-122-5p, a type of small non-coding RNA, was dysregulated in non-small cell lung cancer (NSCLC) cell-derived EVs. In this study, we found that miR-122-5p was selectively sorted and secreted into lung cancer EVs through binding to RNA-binding protein hnRNPA2B1. In addition, we found that hnRNPA2B1 interacted with miR-122-5p through the EXO-motif. The delivering of lung cancer EVs-miR-122-5p promoted the migration of liver cells, which may play roles in establishing a pre-metastatic micro-environment and hepatic metastasis of lung cancer. Importantly, our findings revealed the molecular mechanism that RNA-binding protein controls the selective sorting of tumor-derived EV miR-122-5p, which potentially promotes lung cancer progression.

TsRFun: a comprehensive platform for decoding human tsRNA expression, functions and prognostic value by high-throughput small RNA-Seq and CLIP-Seq data.

tRNA-derived small RNA (tsRNA), a novel type of regulatory small noncoding RNA, plays an important role in physiological and pathological processes. However, the understanding of the functional mechanism of tsRNAs in cells and their role in the occurrence and development of diseases is limited. Here, we integrated multiomics data such as transcriptome, epitranscriptome, and targetome data, and developed novel computer tools to establish tsRFun, a comprehensive platform to facilitate tsRNA research (http://rna.sysu.edu.cn/tsRFun/ or http://biomed.nscc-gz.cn/DB/tsRFun/). tsRFun evaluated tsRNA expression profiles and the prognostic value of tsRNAs across 32 types of cancers, identified tsRNA target molecules utilizing high-throughput CLASH/CLEAR or CLIP sequencing data, and constructed the interaction networks among tsRNAs, microRNAs, and mRNAs. In addition to its data presentation capabilities, tsRFun offers multiple real-time online tools for tsRNA identification, target prediction, and functional enrichment analysis. In summary, tsRFun provides a valuable data resource and multiple analysis tools for tsRNA investigation.

PiRNA-IPdb: a PIWI-bound piRNAs database to mining NGS sncRNA data and beyond

BackgroundPIWI-interacting RNAs (piRNAs) are an abundant single-stranded type of small non-coding RNAs (sncRNAs), which initially were discovered in gonadal cells, with a role as defenders of genomic integrity in the germline, acting against the transposable elements. With a regular size range of 21-35 nt, piRNAs are associated with a PIWI-clade of Argonaute family proteins. The most widely accepted mechanisms of biogenesis for piRNAs involve the transcription of longer precursors of RNAs to be processed, by complexes of proteins, to functional size, preferentially accommodating uridine residues at the 5’ end and 3’ methylation to increase the stability of these molecules. piRNAs have also been detected in somatic cells, with diverse potential functions, indicating their high plasticity and pleiotropic activity. Discovered about two decades ago, piRNAs are a large and versatile type of sncRNA and that remain insufficiently identified and analyzed, through next-generation sequencing (NGS), to evaluate their processing, functions, and biogenesis in different cell types and during development. piRNAs’ distinction from other sncRNAs has led to controversial results and interpretation difficulties when using existing databases because of the heterogeneity of the criteria used in making the distinction.DescriptionWe present “piRNA-IPdb”, a database based uniquely on datasets obtaining after the defining characteristic of piRNAs: those small RNAs bound to PIWI proteins. We selected and analyzed sequences from piRBase that exclusively cover the binding to PIWI. We pooled a total of 18,821,815 sequences from RNA-seq after immunoprecipitation that included the binding to any of the mouse PIWI proteins (MILI, MIWI, or MIWI2).ConclusionsIn summary, we present the characteristics and potential use of piRNA-IPdb database for the analysis of bona fide piRNAs.

MicroRNAs in Transforming Growth Factor-Beta Signaling Pathway Associated With Fibrosis Involving Different Systems of the Human Body.

Fibrosis, a major cause of morbidity and mortality, is a histopathological manifestation of many chronic inflammatory diseases affecting different systems of the human body. Two types of transforming growth factor beta (TGF-β) signaling pathways regulate fibrosis: the canonical TGF-β signaling pathway, represented by SMAD-2 and SMAD-3, and the noncanonical pathway, which functions without SMAD-2/3 participation and currently includes TGF-β/mitogen-activated protein kinases, TGF-β/SMAD-1/5, TGF-β/phosphatidylinositol-3-kinase/Akt, TGF-β/Janus kinase/signal transducer and activator of transcription protein-3, and TGF-β/rho-associated coiled-coil containing kinase signaling pathways. MicroRNA (miRNA), a type of non-coding single-stranded small RNA, comprises approximately 22 nucleotides encoded by endogenous genes, which can regulate physiological and pathological processes in fibrotic diseases, particularly affecting organs such as the liver, the kidney, the lungs, and the heart. The aim of this review is to introduce the characteristics of the canonical and non-canonical TGF-β signaling pathways and to classify miRNAs with regulatory effects on these two pathways based on the influenced organ. Further, we aim to summarize the limitations of the current research of the mechanisms of fibrosis, provide insights into possible future research directions, and propose therapeutic options for fibrosis.

Role of microRNA-122 in the development, progression, and diagnosis of liver disease

MicroRNA is a type of small non-coding RNA that participates in multiple links such as cell proliferation and apoptosis by regulating gene expression after transcription. More and more studies have shown that microRNA-122 (miRNA-122) is involved in the development and progression of a variety of liver diseases. With reference to related reports in the literature, this article summarizes advances in the role of miRNA-122 in various liver diseases including nonalcoholic fatty liver disease, hepatitis, liver fibrosis, and liver cancer and analyzes the potential of miRNA-122 as a new noninvasive biomarker, so as to provide a reference for exploring the diagnosis and treatment of liver disease.