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Long-stranded non-coding RNAs (lncRNAs) are RNA molecules that are longer than 200 nucleotides and do not code for proteins. They play a significant role in various biological processes, including epigenetics, cell cycle, and cell differentiation. Many studies have shown that the occurrence of human cancer is closely related to the abnormal expression of lncRNA. In recent years, lncRNAs have been a hot topic in cancer research. TRPM2-AS, a novel lncRNA, is aberrantly expressed in many human cancers, and its overexpression is strongly linked to poor clinical outcomes in patients. It has been demonstrated that TRPM2-AS acts as a ceRNA, participates in signaling pathways, and interacts with biological proteins and other molecular mechanisms to regulate gene expression. In addition, it can regulate the proliferation, migration, invasion, apoptosis, and treatment resistance of cancer cells. As a result, TRPM2-AS may be a potential target for cancer treatment and a possible biomarker for cancer prognosis. This review outlined the expression, biological processes, and molecular mechanisms of TRPM2-AS in various malignancies, and discussed potential therapeutic uses. [ABSTRACT FROM AUTHOR]

Background: Renal cell carcinoma (RCC) is one of the most common malignant tumor worldwide. Metastasis is a leading case of cancer-related deaths of RCC. Circular RNAs (circRNAs), a class of noncoding RNAs, have emerged as important regulators in cancer metastasis. However, the functional effects and regulatory mechanisms of circRNAs on RCC metastasis remain largely unknown. Methods: High-throughput RNA sequencing techniques were performed to analyze the expression profiles of circRNAs and mRNAs in highly and poorly invasive clear cell renal cell carcinoma (ccRCC) cell lines. Functional experiments were performed to unveil the regulatory role of circPPAP2B in the proliferation and metastatic capabilities of ccRCC cells. RNA pulldown, Mass spectrometry analysis, RNA methylation immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), co-immunoprecipitation (CoIP), next-generation RNA-sequencing and double luciferase experiments were employed to clarify the molecular mechanisms by which circPPAP2B promotes ccRCC metastasis. Results: In this study, we describe a newly identified circular RNA called circPPAP2B, which is overexpressed in highly invasive ccRCC cells, as determined through advanced high-throughput RNA sequencing techniques. Furthermore, we observed elevated circPPAP2B in ccRCC tissues, particularly in metastatic ccRCC tissues, and found it to be associated with poor prognosis. Functional experiments unveiled that circPPAP2B actively stimulates the proliferation and metastatic capabilities of ccRCC cells. Mechanistically, circPPAP2B interacts with HNRNPC in a m6A-dependent manner to facilitate HNRNPC nuclear translocation. Subcellular relocalization was dependent upon nondegradable ubiquitination of HNRNPC and stabilization of an HNRNPC/Vimentin/Importin α7 ternary complex. Moreover, we found that circPPAP2B modulates the interaction between HNRNPC and splicing factors, PTBP1 and HNPNPK, and regulates pre-mRNA alternative splicing. Finally, our studies demonstrate that circPPAP2B functions as a miRNA sponge to directly bind to miR-182-5p and increase CYP1B1 expression in ccRCC. Conclusions: Collectively, our study provides comprehensive evidence that circPPAP2B promotes proliferation and metastasis of ccRCC via HNRNPC-dependent alternative splicing and miR-182-5p/CYP1B1 axis and highlights circPPAP2B as a potential therapeutic target for ccRCC intervention. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are endogenously encoded small RNAs that post-transcriptionally regulate gene expression and play essential roles in numerous developmental and physiological processes. Currently, little information on the transcriptome and tissue-specific expression of miRNAs is available in the model non-edible oilseed crop castor bean (Ricinus communis L.), one of the most important non-edible oilseed crops cultivated worldwide. Recent advances in sequencing technologies have allowed the identification of conserved and novel miRNAs in many plant species. Here, we used high-throughput sequencing technologies to identify and characterize the miRNAs in castor bean. Results: Five small RNA libraries were constructed for deep sequencing from root tips, leaves, developing seeds (at the initial stage, seed1; and at the fast oil accumulation stage, seed2) and endosperms in castor bean. High-throughput sequencing generated a large number of sequence reads of small RNAs in this study. In total, 86 conserved miRNAs were identified, including 63 known and 23 newly identified. Sixteen miRNA isoform variants in length were found from the conserved miRNAs of castor bean. MiRNAs displayed diverse organ-specific expression levels among five libraries. Combined with criteria for miRNA annotation and a RT-PCR approach, 72 novel miRNAs and their potential precursors were annotated and 20 miRNAs newly identified were validated. In addition, new target candidates for miRNAs newly identified in this study were proposed. Conclusions: The current study presents the first high-throughput small RNA sequencing study performed in castor bean to identify its miRNA population. It characterizes and increases the number of miRNAs and their isoforms identified in castor bean. The miRNA expression analysis provides a foundation for understanding castor bean miRNA organ-specific expression patterns. The present study offers an expanded picture of miRNAs for castor bean and other members in the family Euphorbiaceae. [ABSTRACT FROM AUTHOR]

Polyphenism is a successful strategy adopted by organisms to adapt to environmental changes. Brown planthoppers (BPH, Nilaparvata lugens) develop two wing phenotypes, including long-winged (LW) and short-winged (SW) morphs. Though insulin receptor (InR) and juvenile hormone (JH) have been known to regulate wing polyphenism in BPH, the interaction between these regulators remains largely elusive. Here, we discovered that a conserved microRNA, miR-34, modulates a positive autoregulatory feedback loop of JH and insulin/IGF signaling (IIS) pathway to control wing polyphenism in BPH. Nlu-miR-34 is abundant in SW BPHs and suppresses NlInR1 by targeting at two binding sites in the 3’UTR of NlInR1. Overexpressing miR-34 in LW BPHs by injecting agomir-34 induces the development towards SW BPHs, whereas knocking down miR-34 in SW BPHs by injecting antagomir-34 induces more LW BPHs when another NlInR1 suppressor, NlInR2, is also suppressed simultaneously. A cis-response element of Broad Complex (Br-C) is found in the promoter region of Nlu-miR-34, suggesting that 20-hydroxyecdysone (20E) might be involved in wing polyphenism regulation. Topic application of 20E downregulates miR-34 expression but does not change wing morphs. On the other hand, JH application upregulates miR-34 expression and induces more SW BPH. Moreover, knocking down genes in IIS pathway changes JH titers and miR-34 abundance. In all, we showed that miRNA mediates the cross talk between JH, 20E and IIS pathway by forming a positive feedback loop, uncovering a comprehensive regulation mechanism which integrates almost all known regulators controlling wing polyphenism in insects. [ABSTRACT FROM AUTHOR]

Centromere is a specialized chromatin domain that plays a vital role in chromosome segregation. In most eukaryotes, centromere is surrounded by the epigenetically distinct heterochromatin domain. Heterochromatin has been shown to contribute to centromere function, but the precise role of heterochromatin in centromere specification remains elusive. Centromeres in most eukaryotes, including fission yeast (Schizosaccharomyces pombe), are defined epigenetically by the histone H3 (H3) variant CENP-A. In contrast, the budding yeast Saccharomyces cerevisiae has genetically-defined point centromeres. The transition between regional centromeres and point centromeres is considered as one of the most dramatic evolutionary events in centromere evolution. Here we demonstrated that Cse4, the budding yeast CENP-A homolog, can localize to centromeres in fission yeast and partially substitute fission yeast CENP-ACnp1. But overexpression of Cse4 results in its localization to heterochromatic regions. Cse4 is subject to efficient ubiquitin-dependent degradation in S. pombe, and its N-terminal domain dictates its centromere distribution via ubiquitination. Notably, without heterochromatin and RNA interference (RNAi), Cse4 fails to associate with centromeres. We showed that RNAi-dependent heterochromatin mediates centromeric localization of Cse4 by protecting Cse4 from ubiquitin-dependent degradation. Heterochromatin also contributes to the association of native CENP-ACnp1 with centromeres via the same mechanism. These findings suggest that protection of CENP-A from degradation by heterochromatin is a general mechanism used for centromere assembly, and also provide novel insights into centromere evolution. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are endogenous molecules longer than 200 nucleotides, and lack coding potential. LncRNAs that interact with microRNAs (miRNAs) are known as a competing endogenous RNAs (ceRNAs) and have the ability to regulate the expression of target genes. The ceRNAs play an important role in the initiation and progression of various cancers. However, until now, there is no a database including a collection of experimentally verified, human ceRNAs. We developed the LncCeRBase database, which encompasses 432 lncRNA–miRNA–mRNA interactions, including 130 lncRNAs, 214 miRNAs and 245 genes from 300 publications. In addition, we compiled the signaling pathways associated with the included lncRNA–miRNA–mRNA interactions as a tool to explore their functions. LncCeRBase is useful for understanding the regulatory mechanisms of lncRNA. Database URL: http://lnccerbase.it1004.com [ABSTRACT FROM AUTHOR]

Abstract: MicroRNAs (miRNA) participate in regulating diverse biological pathways by translational repression in animals. They have attracted increasing attention recently. However, little work has been done on the miRNA genes in agriculturally important pests. Because the transcripts of most miRNA genes are the products of type-II RNA polymerase, pri-miRNA has a poly(A) tail and appears in expressed sequence tags (EST). We developed a computational pipeline to identify miRNA genes from insect ESTs. First, 980,697 ESTs from 63 insects were collected and used to search the nr database. The ESTs which did not share significant similarities with any known protein-coding genes were treated as non-coding ESTs. Next, known mature miRNAs were used to align with non-coding ESTs. The ESTs which contain the sequence of mature miRNA were treated as candidate ESTs. Finally, putative precursors were extracted flanking the mature miRNA region in candidate ESTs and evaluated by the Triplet-SVM algorithm. As a result, 86 miRNAs from 30 insect species were found based on a strict criterion while 330 miRNAs from 51 species were found based on a loose criterion. Evolution analysis indicated that mir-467, mir-297 and mir-466 were the highest conserved miRNA families in insects. To confirm the reliability of putative insect miRNAs, the expression profile of nine predicted miRNAs in Locusta migratoria was investigated. Eight miRNAs were successfully detected by RT-PCR. Most miRNAs were expressed ubiquitously at all examined tissues and developmental stages whereas Lmi-mir-509 was specifically expressed in the thorax of the 2nd, 4th and 5th instars and adult locust. In all, our work reported an efficient computational strategy for predicting miRNA genes from insect ESTs and presented tens of miRNAs in diverse insect species which are expected to participate in many important physiological processes. [ABSTRACT FROM AUTHOR]

Abstract: MicroRNAs (miRNAs) have recently received much interest for their role in post-transcriptional regulation. However, the study of miRNA transcription lags behind that of gene cloning and functional analysis. The MiR-281 in Drosophila melanogaster is located in the first intron of isoform RA of the ornithine decarboxylase antizyme (ODA) gene. ODA has three isoforms because of alternative transcription start sites (TSSs). Expression profile analysis indicated that miR-281 is not co-expressed with any ODA isoform. We amplified the primary transcripts of miR-281 using the RACE technique. The pri-miRNA is 2149bp with a poly (A) tail and a canonical polyadenylation signal (AATAAA). Chromatin immunoprecipitation analysis confirmed the binding of hypophosphorylated Pol-II and the transcription factor Myc at the core miR-281 promoter region. The abundance of miR-281 does not correlate, either positively or negatively, with the expression of any ODA isoform, indicating that ODA has little influence on the transcription of miR-281. [Copyright &y& Elsevier]