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Vegetation of various heights widely co-exists in natural rivers and wetlands, where the ecological environment and flow process are affected by the riparian vegetation, which has drawn great attention in river engineering and aquatic environmental management. Majority of studies in the past have been mainly focused on the understanding of flow through vegetation of single-layered vegetation. However, in natural riverine environments, mixing vegetation with different heights often occurs in natural rivers, which have a different effect on the flow than the single-layered vegetation does. In a flow condition under multiple layered vegetation, it is limited known about the impact of such vegetation on the flow velocity of channel, which is pre-requisite for many problems in river engineering and environmental management. In this paper, a novel experiment was designed to study the flow characteristics in an open-channel with vegetation of three different heights that exists on the channel bed, with a focus on the effect of the vegetation on the velocity distribution. Experiments were conducted in both partially submerged and fully submerged conditions. Three heights of dowels, 10, 15 and 20 cm, were used to mimic rigid vegetation in a staggered pattern for each type of dowel. Velocities at various locations across a section of channel were measured by Acoustic Doppler Velocimetry (ADV) and propeller velocimetry. Experimental results showed that the vertical velocity distribution is affected by vegetation heights. The results also revealed that the vegetation height have significant impact on the vertical distribution of velocity between and behind the vegetation. The vertical change of velocity behind TP (tall vegetation) and MP (medium vegetation) increases slowly beneath medium vegetation’s height (15cm) and then rapidly increases to the water surface. While the vertical change of velocity behind SP (short vegetation) and BP (blank space between vegetation) decreases a short amount beneath water height 5cm and increases rapidly to the water surface. Generally, the steamwise velocities at short vegetation zone and blank space are larger than tall vegetation zone and medium vegetation zone. These findings on the flow with multiple layered vegetation would be helpful for riparian management practices to maintain healthy ecological and habitat zones.

Muscle satellite cells (SCs) are responsible for muscle homeostasis and regeneration and lncRNAs play important roles in regulating SC activities. Here, in this study, we identify PAM (Pax7 Associated Muscle lncRNA) that is induced in activated/proliferating SCs upon injury to promote SC proliferation as myoblast cells. PAM is generated from a myoblast-specific super-enhancer (SE); as a seRNA it binds with a number of target genomic loci predominantly in trans. Further studies demonstrate that it interacts with Ddx5 to tether PAM SE to its inter-chromosomal targets Timp2 and Vim to activate the gene expression. Lastly, we show that PAM expression is increased in aging SCs, which leads to enhanced inter-chromosomal interaction and target genes upregulation. Altogether, our findings identify PAM as a previously unknown lncRNA that regulates both SC proliferation and aging through its trans gene regulatory activity.

A tight couple makes messenger RNAs Gene expression in eukaryotes first requires transcription of DNA to an RNA copy and then splicing to form the final, processed messenger RNA (mRNA). Zhang et al. investigated how gene transcription and RNA splicing are physically coupled. Using cryo–electron microscopy, they resolved the molecular structure of a complex of the transcription enzyme RNA polymerase II with part of the splicing machinery, the U1 small nuclear ribonucleoprotein particle. The results provide important details for our understanding of coupled mRNA production. Science , this issue p. 305

The functional study of lncRNAs in skeletal muscle satellite cells (SCs) remains at the infancy stage. Here we identify SAM (Sugt1 asssociated muscle) lncRNA that is enriched in the proliferating myoblasts. Global deletion of SAM has no overt effect on mice but impairs adult muscle regeneration following acute damage; it also exacerbates the chronic injury-induced dystrophic phenotype in mdx mice. Consistently, inducible deletion of SAM in SCs leads to deficiency in muscle regeneration. Further examination reveals that SAM loss results in a cell-autonomous defect in the proliferative expansion of myoblasts. Mechanistically, we find SAM interacts and stabilizes Sugt1, a co-chaperon protein key to kinetochore assembly during cell division. Loss of SAM or Sugt1 both disrupts kinetochore assembly in mitotic cells due to the mislocalization of two components: Dsn1 and Hec1. Altogether, our findings identify SAM as a regulator of SC proliferation through facilitating Sugt1 mediated kinetochore assembly during cell division., Long noncoding RNA SAM (Sugt1 associated muscle) is upregulated in the proliferating myoblast cells. Here the authors investigate SAM knockout mice and suggest that SAM binds and stabilizes Sugt1, a co-chaperone protein that regulates kinetochore assembly.

Conventional Kirchhoff prestack time migration based on the hyperbolic moveout can cause ambiguity in laterally inhomogeneous media, because the root mean square velocity corresponds to a one‐dimensional model under the horizontal layer assumption; it does not include the lateral variations. The shot/receiver configuration with different offsets and azimuths should adopt different migration velocities as they contribute to a single image point. Therefore, we propose to use an offset‐vector to describe the lateral variations through an offset‐dependent velocity corresponding to the difference in offset from surface points to the image point. The offset‐vector is decomposed into orthogonal directions along the in‐line and cross‐line directions so that the single velocity can be expressed as a series of actual velocities. We use a simple Snell's law‐based ray tracing to calculate the travel time recorded at the image point and convert the travel time to an equivalent velocity corresponding to a pseudo‐straight ray. The double‐square‐root equation using such an equivalent velocity in the offset‐vector domain is non‐hyperbolic and asymmetrical, which improves the accuracy of the migration. Numerical examples using the Marmousi model and a wide azimuth field data show that the proposed method can achieve reasonable accuracy and significantly enhances the imaging of complex structures.

In order to improve the effect of the medical information automatic translation system, based on the text feature recognition technology of medical image, this paper constructs an automatic translation system that can recognize medical images. On the basis of the medical information image retrieval based on the combination of text information and visual information, this paper uses automatic image annotation technology and semantic similarity calculation method to extract the text and semantic features of medical information images. Then, this paper uses the inherent multi-information fusion capability of the Bayesian inference network to fuse the text features of medical information images and the semantic features of image content together to realize medical information image retrieval. Finally, this paper designs experiments to test the performance of the medical information automatic translation system. The research shows that the system constructed in this paper has certain effects.

Muscle satellite cells (SCs) are responsible for muscle homeostasis and regeneration; and lncRNAs play important roles in regulating SC activities. Here in this study, we identify PAM-1 (Pax7 Associated Muscle lncRNA) that is induced in activated SCs to promote SC activation into myoblast cells upon injury. PAM-1 is generated from a myoblast specific super-enhancer (SE); as a seRNA it binds with a number of target genomic loci predominantly in trans. Further studies demonstrate that it interacts with Ddx5 to tether PAM-1 SE to it inter-chromosomal targets Timp2 and Vim to activate the gene expression. Lastly, we show that PAM-1 expression is increased in aging SCs, which leads to enhanced inter-chromosomal interaction and target genes up-regulation. Altogether, our findings identify PAM-1 as a previously unknown lncRNA that regulates both SC activation and aging through its trans gene regulatory activity.

A good scoring function is necessary for ab inito prediction of RNA tertiary structures. In this study, we explored the power of a machine learning based approach as a scoring function. Compared with the traditional scoring functions, the present approach is more flexible in incorporating different kinds of features; it is also free of the difficult problem of choosing the reference state. Two multi-layer neural networks were constructed and trained. They took RNA a structural candidate as input and then output its likeness score that evaluates the likeness of the candidate to the native structure. The first network was working at the coarse-grained level of RNA structures, while the second at the all-atom level. We also built an RNA database and split it into the training, validation, and testing sets, containing 322, 70, and 70 RNAs, respectively. Each RNA was accompanied with 300 decoys generated by high-temperature molecular dynamics simulations. The networks were trained on the training set and then optimized with an early-stop strategy, based on the loss of the validation set. We then tested the performance of the networks on the testing set. The results were found to be consistently better than a recent knowledge-based all-atom potential.

In this study, 196 strains of actinomycetes isolated from marshland soil samples were tested for molluscicidal activity against Oncomelania hupensis. Five strains demonstrated molluscicidal activity, of which the molluscicidal efficiency of Actinomycetes strain A183 was the maximum. After the fermentation supernatant of actinomycetes A183 was extracted with ethyl acetate (EWEA), the LC50 of the EWEA after leaching for 48 h and 72 h were 0.2688 and 0.2195 mg/L, respectively. The effect of EWEA on the key points of energy metabolism was determined. We noted that 1 mg/L of EWEA (A813) significantly reduced the activity of mitochondrial respiratory chain complex I (P0.05), while no significant changes were observed in the activities of complexes II, III, and IV. In addition, EWEA (A813) could decrease the membrane potential of O. hupensis purified mitochondria in vitro. The LC50 of the 3 uncoupler (FCCP, DNP, and Tyrphostin A9) after immersion for 24 h were 0.065, 0.135, and 0.110 mg/L, respectively; LC50 after 48 h treatment was 0.064, 0.124, and 0.082 mg/L, respectively; LC50 after 72 h treatment was 0.063, 0.129, and 0.061 mg/L, respectively, and all uncoupler showed strong molluscicidal activities, demonstrating that the mitochondrial membrane potential uncoupling is a potential target for molluscicides against O. hupensis. Moreover, the molluscicidal active substance of strain A183 needs to be further isolated, purified, and structurally characterized considering its promising potential applications.

Adult muscle stem cells, also known as satellite cells (SCs), play pivotal roles in muscle regeneration, and long non-coding RNA (lncRNA) functions in SCs remain largely unknown. Here, we identify a lncRNA, Lockd, which is induced in activated SCs upon acute muscle injury. We demonstrate that Lockd promotes SC proliferation; deletion of Lockd leads to cell-cycle arrest, and in vivo repression of Lockd in mouse muscles hinders regeneration process. Mechanistically, we show that Lockd directly interacts with RNA helicase DHX36 and the 5'end of Lockd possesses the strongest binding with DHX36. Furthermore, we demonstrate that Lockd stabilizes the interaction between DHX36 and EIF3B proteins; synergistically, this complex unwinds the RNA G-quadruplex (rG4) structure formed at Anp32e mRNA 5' UTR and promotes the translation of ANP32E protein, which is required for myoblast proliferation. Altogether, our findings identify a regulatory Lockd/DHX36/Anp32e axis that promotes myoblast proliferation and acute-injury-induced muscle regeneration.

Super-enhancers (SEs) are cis-regulatory elements enriching lineage specific key transcription factors (TFs) to form hotspots. A paucity of identification and functional dissection promoted us to investigate SEs during myoblast differentiation. ChIP-seq analysis of histone marks leads to the uncovering of SEs which remodel progressively during the course of differentiation. Further analyses of TF ChIP-seq enable the definition of SE hotspots co-bound by the master TF, MyoD and other TFs, among which we perform in-depth dissection for MyoD/FoxO3 interaction in driving the hotspots formation and SE activation. Furthermore, using Myogenin as a model locus, we elucidate the hierarchical and complex interactions among hotspots during the differentiation, demonstrating SE function is propelled by the physical and functional cooperation among hotspots. Finally, we show MyoD and FoxO3 are key in orchestrating the Myogenin hotspots interaction and activation. Altogether our results identify muscle-specific SEs and provide mechanistic insights into the functionality of SE.

The anaphase-promoting complex/cyclosome (APC/C) orchestrates cell cycle progression by controlling the temporal degradation of specific cell cycle regulators. Although cyclin A2 and cyclin B1 are both targeted for degradation by the APC/C, during the spindle assembly checkpoint (SAC), the mitotic checkpoint complex (MCC) represses APC/C’s activity towards cyclin B1, but not cyclin A2. Through structural, biochemical and in vivo analysis, we identify a non-canonical D box (D2) that is critical for cyclin A2 ubiquitination in vitro and degradation in vivo. During the SAC, cyclin A2 is ubiquitinated by the repressed APC/C-MCC, mediated by the cooperative engagement of its KEN and D2 boxes, ABBA motif, and the cofactor Cks. Once the SAC is satisfied, cyclin A2 binds APC/C-Cdc20 through two mutually exclusive binding modes, resulting in differential ubiquitination efficiency. Our findings reveal that a single substrate can engage an E3 ligase through multiple binding modes, affecting its degradation timing and efficiency., During the spindle assembly checkpoint, the activity of the anaphase promoting complex/cyclosome (APC/C) is repressed, yet cyclin A2 evades the checkpoint and is targeted for degradation. Here, the authors define the underlying mechanism and reveal that cyclin A2 engages the APC/C in multiple binding modes.

In eukaryotes, the anaphase-promoting complex (APC/C, also known as the cyclosome) regulates the ubiquitin-dependent proteolysis of specific cell-cycle proteins to coordinate chromosome segregation in mitosis and entry into the G1 phase. The catalytic activity of the APC/C and its ability to specify the destruction of particular proteins at different phases of the cell cycle are controlled by its interaction with two structurally related coactivator subunits, Cdc20 and Cdh1. Coactivators recognize substrate degrons, and enhance the affinity of the APC/C for its cognate E2 (refs 4-6). During mitosis, cyclin-dependent kinase (Cdk) and polo-like kinase (Plk) control Cdc20- and Cdh1-mediated activation of the APC/C. Hyperphosphorylation of APC/C subunits, notably Apc1 and Apc3, is required for Cdc20 to activate the APC/C, whereas phosphorylation of Cdh1 prevents its association with the APC/C. Since both coactivators associate with the APC/C through their common C-box and Ile-Arg tail motifs, the mechanism underlying this differential regulation is unclear, as is the role of specific APC/C phosphorylation sites. Here, using cryo-electron microscopy and biochemical analysis, we define the molecular basis of how phosphorylation of human APC/C allows for its control by Cdc20. An auto-inhibitory segment of Apc1 acts as a molecular switch that in apo unphosphorylated APC/C interacts with the C-box binding site and obstructs engagement of Cdc20. Phosphorylation of the auto-inhibitory segment displaces it from the C-box-binding site. Efficient phosphorylation of the auto-inhibitory segment, and thus relief of auto-inhibition, requires the recruitment of Cdk-cyclin in complex with a Cdk regulatory subunit (Cks) to a hyperphosphorylated loop of Apc3. We also find that the small-molecule inhibitor, tosyl-l-arginine methyl ester, preferentially suppresses APC/C(Cdc20) rather than APC/C(Cdh1), and interacts with the binding sites of both the C-box and Ile-Arg tail motifs. Our results reveal the mechanism for the regulation of mitotic APC/C by phosphorylation and provide a rationale for the development of selective inhibitors of this state.

The detection of exogenous plant microRNAs in human/animal plasma/sera lies at the foundation of exploring their cross-kingdom regulatory functions. It is necessary to establish a standard operation procedure to promote study in this nascent field. In this study, 18 plant miRNAs were assessed in watermelon juice and mixed fruits by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). CT values, no-template controls and standard curves for each miRNA were used to evaluate the specificity and sensitivity of qRT-PCR and to obtain concentrations. Sixteen miRNAs were selected and measured in human plasma from volunteers after drinking juice. The CT values of 6 plant miRNAs in human plasma fell outside the linear ranges of their standard curves. The remaining 10 miRNAs were present at high basal levels, and 6 of them showed a dynamic physiological pattern in plasma (absorption rates of 0.04% to 1.31%). Northern blotting was used to confirm the qRT-PCR results. Critical issues such as RNA extraction and internal controls were also addressed.

The anaphase promoting complex or cyclosome (APC/C) is a large multi-subunit E3 ubiquitin ligase that orchestrates cell cycle progression by mediating the degradation of important cell cycle regulators. During the two decades since its discovery, much has been learnt concerning its role in recognizing and ubiquitinating specific proteins in a cell-cycle-dependent manner, the mechanisms governing substrate specificity, the catalytic process of assembling polyubiquitin chains on its target proteins, and its regulation by phosphorylation and the spindle assembly checkpoint. The past few years have witnessed significant progress in understanding the quantitative mechanisms underlying these varied APC/C functions. This review integrates the overall functions and properties of the APC/C with mechanistic insights gained from recent cryo-electron microscopy (cryo-EM) studies of reconstituted human APC/C complexes.

Malat1 is one of the most abundant long non-coding RNAs in various cell types; its exact cellular function is still a matter of intense investigation. In this study we characterized the function of Malat1 in skeletal muscle cells and muscle regeneration. Utilizing both in vitro and in vivo assays, we demonstrate that Malat1 has a role in regulating gene expression during myogenic differentiation of myoblast cells. Specifically, we found that knockdown of Malat1 accelerates the myogenic differentiation in cultured cells. Consistently, Malat1 knockout mice display enhanced muscle regeneration after injury and deletion of Malat1 in dystrophic mdx mice also improves the muscle regeneration. Mechanistically, in the proliferating myoblasts, Malat1 recruits Suv39h1 to MyoD-binding loci, causing trimethylation of histone 3 lysine 9 (H3K9me3), which suppresses the target gene expression. Upon differentiation, the pro-myogenic miR-181a is increased and targets the nuclear Malat1 transcripts for degradation through Ago2-dependent nuclear RNA-induced silencing complex machinery; the Malat1 decrease subsequently leads to the destabilization of Suv39h1/HP1β/HDAC1-repressive complex and displacement by a Set7-containing activating complex, which allows MyoD trans-activation to occur. Together, our findings identify a regulatory axis of miR-181a-Malat1-MyoD/Suv39h1 in myogenesis and uncover a previously unknown molecular mechanism of Malat1 action in gene regulation.

Ebola virus (EBOV), a member of the filovirus family, is an enveloped negative-sense RNA virus that causes lethal infections in humans and primates. Recently, more than 1000 people have been killed by the Ebola virus disease in Africa, yet no specific treatment or diagnostic tests for EBOV are available. In this study, we identified two putative viral microRNA precursors (pre-miRNAs) and three putative mature microRNAs (miRNAs) derived from the EBOV genome. The production of the EBOV miRNAs was further validated in HEK293T cells transfected with a pcDNA6.2-GW/EmGFP-EBOV-pre-miRNA plasmid, indicating that EBOV miRNAs can be produced through the cellular miRNA processing machinery. We also predicted the potential target genes of these EBOV miRNAs and their possible biological functions. Overall, this study reports for the first time that EBOV may produce miRNAs, which could serve as non-invasive biomarkers for the diagnosis and prognosis of EBOV infection and as therapeutic targets for Ebola viral infection treatment.

Recently, numerous studies have documented the importance of microRNAs (miRNAs) as an essential cornerstone of the genetic system. Although RNA is usually considered an unstable molecule because of the ubiquitous ribonuclease, miRNAs are now known to circulate in the bloodstream and other body fluids in a stable, cell-free form. Importantly, extracellular miRNAs are aberrantly present in plasma, serum, and other body fluids during the pathogenesis of many diseases and, thus, are promising noninvasive or minimally invasive biomarkers to assess the pathological status of the body. However, the origin and biological function of extracellular miRNAs remains incompletely understood. In this review, we summarize the recent literature on the biogenesis and working models of extracellular miRNAs, and we highlight the impact of extending these ongoing extracellular miRNA studies to clinical applications.

High density lipoproteins (HDL) have been successfully reconstructed to deliver a large number of lipophilic drugs. Here, discoidal and spherical recombinant HDL loaded with cardiovascular drug tanshinone IIA (TA) were constructed (TA-d-rHDL and TA-s-rHDL), respectively. And next their in vitro physiochemical and biomimetic properties were characterized. Furthermore, pharmacokinetics, atherosclerotic lesions targeting effects and antiatherogenic efficacies were elaborately performed and compared in atherosclerotic New Zealand White (NZW) rabbits. In vitro characterizations results showed that both TA-d-rHDL and TA-s-rHDL had nano-size diameter, high entrapment efficiency (EE) and drug-loading capacity (DL). Additionally, similar to their native counterparts, TA-d-rHDL maintained remodeling behaviors induced by lecithin cholesterol acyltransferase (LCAT), and TA leaked during remodeling behaviors. Pharmacokinetic studies manifested that both TA-d-rHDL and TA-s-rHDL markedly improved pharmacokinetic behaviors of TA in vivo. Ex vivo imaging demonstrated that both d-rHDL and s-rHDL bound more avidly to atherosclerotic lesions than to normal vessel walls, and s-rHDL had better targeting effect than d-rHDL. Pharmacodynamic tests illustrated that both TA-d-rHDL and TA-s-rHDL had much stronger antiatherogenic efficacies than conventional TA nanostructured lipid carriers (TA-NLC), TA liposomes (TA-L) and commercially available preparation Sulfotanshinone Sodium Injection (SSI). Moreover, TA-s-rHDL had more potent antiatherogenic efficacies than TA-d-rHDL. Collectively our studies indicated that rHDL could be exploited as potential delivery vehicles of TA targeting atherosclerotic lesions as well as synergistically improving efficacies, especially for s-rHDL.

In this work, lanthanide $$\beta $$ -diketonate complexes Ln(btfa) $${}_{3} \cdot 2\hbox {H}_{2}$$ O (Ln $$^{3+}$$ : Eu $$^{3+}$$ , Sm $$^{3+ }$$ , and Tb $$^{3+}$$ ; btfa: 4,4,4-trifluoro-l-phenyl-1,3-butanedione) were incorporated into silica gels by a sol–gel method. Photoacoustic (PA) spectra of these complex-doped silica samples were measured and studied. The PA intensity of the $$\beta $$ -diketonate ligand is nearly the same for lanthanide complexes in wet gels. After heat treatment at 150 $$^{\circ }$$ C, however, the PA intensity of the ligand increases for Eu $$^{3+}$$ , Sm $$^{3+}$$ , and Tb $$^{3+}$$ complexes in silica gels, respectively. Different PA intensities of the samples are interpreted by comparison with their luminescence spectra. The luminescence result is consistent with the PA spectra. The result indicates that lanthanide $$\beta $$ -diketonate complexes cannot be formed in silica gels without a suitable heat treatment. Moreover, the relaxation process model is proposed based on the PA and luminescence results.

In this work, $$\hbox {Pr}^{3+}$$ -doped titania nanomaterials were prepared by a sol–gel method. The structural variations of the samples during the phase transitions were studied by using the $$\hbox {Pr}^{3+}$$ ion as a photoacoustic spectral probe. The result shows that for the gel sample heated at $$80\,^{\circ }\hbox {C}$$ , the coordination environment of $$\hbox {Pr}^{3+}$$ is similar to that of its aqueous ion. The f–f transitions of $$\hbox {Pr}^{3+}$$ exhibit a continuous red shift along with the gel-to-anatase transition, indicating an increase of the ‘degree of covalency’ for the $$\hbox {Pr}^{3+}$$ bonding. For the sample calcined at $$1100\,^{\circ }\hbox {C}$$ , however, the f–f transitions of $$\hbox {Pr}^{3+}$$ show obvious blue shift. This can be attributed to the segregation of $$\hbox {Pr}^{3+}$$ ions to the external surface during the anatase-to-rutile transition, forming $$\hbox {Pr}_{4}\hbox {Ti}_{9}\hbox {O}_{24}$$ . The stabilization effect of the doped $$\hbox {Pr}^{3+ }$$ ions on the anatase phase of the samples is also discussed.

Although piwi-interacting RNAs (piRNAs) play pivotal roles in spermatogenesis, little is known about piRNAs in the seminal plasma of infertile males. In this study, we systematically investigated the profiles of seminal plasma piRNAs in infertile males to identify piRNAs that are altered during infertility and evaluate their diagnostic value. Seminal plasma samples were obtained from 211 infertile patients (asthenozoospermia and azoospermia) and 91 fertile controls. High-throughput sequencing technology was employed to screen piRNA profiles in seminal plasma samples pooled from healthy controls and infertile patients. The results identified 61 markedly altered piRNAs in infertile patient groups compared with control group. Next, a quantitative RT-PCR assay was conducted in the training and validation sets to measure and confirm the concentrations of altered piRNAs. The results identified a panel of 5 piRNAs that were significantly decreased in seminal plasma of infertile patients compared with healthy controls. ROC curve analysis and risk score analysis revealed that the diagnostic potential of these 5 piRNAs to distinguish asthenozoospermic and azoospermic individuals from healthy controls was high. In summary, this study identifies a panel of piRNAs that can accurately distinguish fertile from infertile males. This finding may provide pathophysiological clues about the development of infertility.

Ultrashort-pulsed lasers have been attracting worldwide interest in science and engineering. Studying the ther- mal deformation induced by ultrashort-pulsed lasers is important for preventing thermal damage. This article presents a new numerical method for studying thermal deformation in 3D double-layered film micro-structures exposed to ultras- hort-pulsed lasers. The method is demonstrated by investigating thermal deformations in a 3D double-layered thin film and a 3D double-layered sphere, respectively.

Background Although human cancers have heterogeneous combinations of altered oncogenes, some crucial genes are universally dysregulated in most cancers. One such gene, FEAT (faint expression in normal tissues, aberrant overexpression in tumors), is uniformly overexpressed in a variety of human cancers and plays an important role in tumorigenesis by suppressing apoptosis. However, the precise molecular mechanism through which FEAT is upregulated during tumorigenesis remains largely unknown. Methods In this study, we used bioinformatic analyses to search for miRNAs that potentially target FEAT. We examined the expression of FEAT protein level by western blotting and miR-16 level by qRT-PCR assay. Cancer cell lines (A549, MCF-7 and Huh-7) with miR-16 upregulation and FEAT silencing were established and the effects on apoptosis of cancer cells in vitro were assessed. Luciferase reporter assay was also performed to investigate the interaction between miR-16 and FEAT. Results We identified a specific target site for miR-16 in the 3′-untranslated region (3′-UTR) of FEAT. Consistent with the bioinformatic analyses, we identified an inverse correlation between the miR-16 and FEAT protein levels in lung cancer, breast cancer, and hepatocellular cancer tissues. We then experimentally validated miR-16 as a direct regulator of FEAT using cell transfection and luciferase assays. Finally, we demonstrated that the repression of FEAT by miR-16 promoted the apoptosis of cancer cells. Conclusions Our findings provide the first clues regarding the role of miR-16 as a tumor suppressor in cancer cells through the inhibition of FEAT translation. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1458-8) contains supplementary material, which is available to authorized users.

Little is known how lincRNAs are involved in skeletal myogenesis. Here we describe the discovery of Linc-YY1 from the promoter of the transcription factor (TF) Yin Yang 1 (YY1) gene. We demonstrate that Linc-YY1 is dynamically regulated during myogenesis in vitro and in vivo. Gain or loss of function of Linc-YY1 in C2C12 myoblasts or muscle satellite cells alters myogenic differentiation and in injured muscles has an impact on the course of regeneration. Linc-YY1 interacts with YY1 through its middle domain, to evict YY1/Polycomb repressive complex (PRC2) from target promoters, thus activating the gene expression in trans. In addition, Linc-YY1 also regulates PRC2-independent function of YY1. Finally, we identify a human Linc-YY1 orthologue with conserved function and show that many human and mouse TF genes are associated with lincRNAs that may modulate their activity. Altogether, we show that Linc-YY1 regulates skeletal myogenesis and uncover a previously unappreciated mechanism of gene regulation by lincRNA.

MicroRNA-200b and microRNA-200c (miR-200b/c) are 2 of the most frequently upregulated oncomiRs in colorectal cancer cells. The role of miR-200b/c during colorectal tumorigenesis, however, remains unclear. In the present study, we report that miR-200b/c can promote colorectal cancer cell proliferation via targeting the reversion-inducing cysteine-rich protein with Kazal motifs (RECK). Firstly, bioinformatics analysis predicted RECK as a conserved target of miR-200b/c. By overexpressing or knocking down miR-200b/c in colorectal cancer cells, we experimentally validated that miR-200b/c are direct regulators of RECK. Secondly, an inverse correlation between the levels of miR-200b/c and RECK protein was found in human colorectal cancer tissues and cell lines. Thirdly, we demonstrated that repression of RECK by miR-200b/c consequently triggered SKP2 (S-phase kinase-associated protein 2) elevation and p27Kip1 (also known as cyclin-dependent kinase inhibitor 1B) degradation in colorectal cancer cells, which eventually promotes cancer cell proliferation. Finally, promoting tumor cell growth by miR-200b/c-targeting RECK was also observed in the xenograft mouse model. Taken together, our results demonstrate that miR-200b/c play a critical role in promoting colorectal tumorigenesis through inhibiting RECK expression and subsequently triggering SKP2 elevation and p27Kip1 degradation.

Long noncoding RNAs (lncRNAs) are key regulators of diverse cellular processes. Recent advances in high-throughput sequencing have allowed for an unprecedented discovery of novel lncRNAs. To identify functional lncRNAs from thousands of candidates for further functional validation is still a challenging task. Here, we present a novel computational framework, lncFunNet (lncRNA Functional inference through integrated Network) that integrates ChIP-seq, CLIP-seq and RNA-seq data to predict, prioritize and annotate lncRNA functions. In mouse embryonic stem cells (mESCs), using lncFunNet we not only recovered most of the functional lncRNAs known to maintain mESC pluripotency but also predicted a plethora of novel functional lncRNAs. Similarly, in mouse myoblast C2C12 cells, applying lncFunNet led to prediction of reservoirs of functional lncRNAs in both proliferating myoblasts (MBs) and differentiating myotubes (MTs). Further analyses demonstrated that these lncRNAs are frequently bound by key transcription factors, interact with miRNAs and constitute key nodes in biological network motifs. Further experimentations validated their dynamic expression profiles and functionality during myoblast differentiation. Collectively, our studies demonstrate the use of lncFunNet to annotate and identify functional lncRNAs in a given biological system.

Introduction ERBB3, one of the four members of the ErbB family of receptor tyrosine kinases, plays an important role in breast cancer etiology and progression. In the present study, we aimed to identify novel miRNAs that can potentially target ERBB3 and their biological functions. Method The expression levels of miR-143/145 and target mRNA were examined by relative quantification RT-PCR, and the expression levels of target protein were detected by Western blot. We used bioinformatic analyses to search for miRNAs that can potentially target ERBB3. Luciferase reporter plasmids were constructed to confirm direct targeting. Furthermore, the biological consequences of the targeting of ERBB3 by miR-143/145 were examined by cell proliferation and invasion assays in vitro and by the mouse xenograft tumor model in vivo. Results We identified an inverse correlation between miR-143/145 levels and ERBB3 protein levels, but not between miR-143/145 levels and ERBB3 mRNA levels, in breast cancer tissue samples. We identified specific targeting sites for miR-143 and miR-145 (miR-143/145) in the 3’-untranslated region (3’-UTR) of the ERBB3 gene and regulate ERBB3 expression. We demonstrated that the repression of ERBB3 by miR-143/145 suppressed the proliferation and invasion of breast cancer cells, and that miR-143/145 showed an anti-tumor effect by negatively regulating ERBB3 in the xenograft mouse model. Interestingly, miR-143 and miR-145 showed a cooperative repression of ERBB3 expression and cell proliferation and invasion in breast cancer cells, such that the effects of the two miRNAs were greater than with either miR-143 or miR-145 alone. Conclusion Taken together, our findings provide the first clues regarding the role of the miR-143/145 cluster as a tumor suppressor in breast cancer through the inhibition of ERBB3 translation. These results also support the idea that different miRNAs in a cluster can synergistically repress a given target mRNA. Electronic supplementary material The online version of this article (doi:10.1186/1476-4598-13-220) contains supplementary material, which is available to authorized users.

Insulin-like growth factor 1 receptor (IGF1R) is a transmembrane receptor that is activated by insulin-like growth factor 1 (IGF-1) and by a related hormone called IGF-2. It belongs to the large class of tyrosine kinase receptors and plays an important role in colorectal cancer etiology and progression. In this study, we used bioinformatic analyses to search for miRNAs that potentially target IGF1R. We identified specific target sites for miR-143 and miR-145 (miR-143/145) in the 3'-untranslated region (3'-UTR) of the IGF1R gene. These miRNAs are members of a cluster of miRNAs that have been reported to exhibit tumor suppressor activity. Consistent with the bioinformatic analyses, we identified an inverse correlation between miR-143/145 levels and IGF1R protein levels in colorectal cancer tissues. By overexpressing miR-143/145 in Caco2, HT29 and SW480 colorectal cancer cells, we experimentally validated that miR-143/145 directly recognizes the 3'-UTR of the IGF1R transcript and regulates IGF1R expression. Furthermore, the biological consequences of the targeting of IGF1R by miR-143/145 were examined by cell proliferation assays in vitro. We demonstrated that the repression of IGF1R by miR-143/145 suppressed the proliferation of Caco2 cells. Taken together, our findings provide evidence for a role of the miR-143/145 cluster as a tumor suppressor in colorectal cancer through the inhibition of IGF1R translation.

SRC, also known as proto-oncogene c-Src, is a non-receptor tyrosine kinase that plays an important role in cancer progression by promoting survival, angiogenesis, proliferation, and invasion pathways. In this study, we found that SRC protein levels were consistently upregulated in lung cancer tissues, but that SRC mRNA levels varied randomly, suggesting that a post-transcriptional mechanism was involved in SRC regulation. Because microRNAs (miRNAs) are powerful post-transcriptional regulators of gene expression, we used bioinformatic analyses to search for miRNAs that potentially target SRC. We identified specific targeting sites for miR-203 in the 3'-untranslated region (3'-UTR) of SRC. We then experimentally validated miR-203 as a direct regulator of SRC using cell transfection and luciferase assays and showed that miR-203 inhibited SRC expression and consequently triggered suppression of the SRC/Ras/ERK pathway. Finally, we demonstrated that the repression of SRC by miR-203 suppressed the proliferation and migration and promoted the apoptosis of lung cancer cells. In summary, this study provides the first clues regarding the role of miR-203 as a tumor suppressor in lung cancer cells through the inhibition of SRC translation.

Background In eukaryotes, miR-16 is an important microRNA (miRNA) that is involved in numerous biological processes. However, it is not fully understood how miR-16 executes its physiological functions. In the present study, we aimed to identify novel miR-16 targets and study their biological functions. Methods Candidate target genes of miR-16 were screened by microarray analysis of mRNA levels in several cancer cell lines with enhanced miR-16. Three bioinformatics algorithms, including TargetScan, PicTar, and miRanda, were used in combination to calculate the miR-16 targets. The expression levels of miR-16 and target mRNA were examined by relative quantification RT-PCR, and the expression levels of target protein were detected by Western blot. Luciferase reporter plasmids were constructed to confirm direct targeting. The effect of miR-16 and target gene on cell viability was evaluated using MTT assays. The effects of miR-16 and target gene on apoptosis and cell cycle distribution were evaluated by flow cytometry analysis. Results By overexpressing miR-16 in several cancer cell lines and measuring global mRNA levels using microarray analysis, we identified 27 genes that may be regulated by miR-16. After the bioinformatics filtering process, 18 genes were selected as candidate miR-16 targets. Furthermore, we experimentally validated three of these candidates, MAP7 (microtubule-associated protein 7), PRDM4 (PR domain containing 4) and CDS2 (CDP-diacylglycerol synthase 2), as direct targets of miR-16. Finally, we demonstrated that miR-16 targeting MAP7 played a critical role in regulating proliferation but not apoptosis and cell cycle progression in cancer cells. Conclusion In summary, the present study identifies several novel miR-16 targets and illustrates a novel function of miR-16 targeting MAP7 in modulating proliferation in cancer cells.

Recently, numerous studies have documented the importance of microRNAs (miRNAs) as an essential cornerstone of the genetic system. Although RNA is usually considered an unstable molecule because of the ubiquitous ribonuclease, miRNAs are now known to circulate in the bloodstream and other body fluids in a stable, cell-free form. Importantly, extracellular miRNAs are aberrantly present in plasma, serum, and other body fluids during the pathogenesis of many diseases and, thus, are promising noninvasive or minimally invasive biomarkers to assess the pathological status of the body. However, the origin and biological function of extracellular miRNAs remains incompletely understood. In this review, we summarize the recent literature on the biogenesis and working models of extracellular miRNAs, and we highlight the impact of extending these ongoing extracellular miRNA studies to clinical applications.

It is Yan Geling’s invariable literary thoughts and feelings that express the real deep affections and experiences of women. As a Chinese American writer, she has invented one Chinese story after another. All her stories are unique, intricate and imbued with deep affectations. In Fusang, Yan Geling revealed the hard, bloody and tragic history of the Chinese immigrants. Her narration is a new annotation of the ancient Chinese femininity, gender relationship and cross-cultural communication. In the novel, the author, basing on cross-cultural communication and combining her personal life experiences with the story, showed deep concern for the survival conditions of the traditional oriental females so as to arouse readers’ rational thought and emotional resonance. Through the vivid feminine imagery living at the bottom of the social ladder, Yan opened the window for readers to spy on feminine primitive potency and explore into the secret buried deep in human nature.