Friend leukemia virus integration 1 (FLI1), an ETS transcription factor family member, acts as an oncogenic driver in hematological malignancies and promotes tumor growth in solid tumors. However, ...little is known about the mechanisms underlying the activation of this proto-oncogene in tumors.
Immunohistochemical staining showed that FLI1 is aberrantly overexpressed in advanced stage and metastatic breast cancers. Using a CRISPR Cas9-guided immunoprecipitation assay, we identify a circular RNA in the FLI1 promoter chromatin complex, consisting of FLI1 exons 4-2-3, referred to as FECR1.Overexpression of FECR1 enhances invasiveness of MDA-MB231 breast cancer cells. Notably, FECR1 utilizes a positive feedback mechanism to activate FLI1 by inducing DNA hypomethylation in CpG islands of the promoter. FECR1 binds to the FLI1 promoter in cis and recruits TET1, a demethylase that is actively involved in DNA demethylation. FECR1 also binds to and downregulates in trans DNMT1, a methyltransferase that is essential for the maintenance of DNA methylation.
These data suggest that FECR1 circular RNA acts as an upstream regulator to control breast cancer tumor growth by coordinating the regulation of DNA methylating and demethylating enzymes. Thus, FLI1 drives tumor metastasis not only through the canonical oncoprotein pathway, but also by using epigenetic mechanisms mediated by its exonic circular RNA.
Carboazidation of alkenes and alkynes holds the promise to construct valuable molecules directly from chemical feedstock therefore is significantly important. Although a few examples have been ...developed, there are still some unsolved problems and lack of universal methods for carboazidation of both alkenes and alkynes. Here we describe an iron-catalyzed rapid carboazidation of alkenes and alkynes, enabled by the oxidative radical relay precursor t-butyl perbenzoate. This strategy enjoys success with a broad scope of alkenes under mild conditions, and it can also work with aryl alkynes which are challenging substrates for carboazidation. A large number of diverse structures, including many kinds of amino acid precursors, fluoroalkylated vinyl azides, other specific organoazides, and 2H-azirines can be easily produced.
One of the biggest obstacles for superhydrophobic films in applications is their poor mechanical resistance. In this research, robust superhydrophobic SiO2 films were constructed on mild steel (MS) ...for corrosion protection by the combination of rough electrodeposited SiO2 (E-SiO2) films and durable polydimethylsiloxane (PDMS) polymer with low surface energy. Results show that the PDMS content has a great effect on the microtopography, wettability, roughness, and wear-resistance of the final films. EIS measurements indicate that as-prepared robust superhydrophobic E-SiO2/PDMS films exhibit good corrosion inhibition efficiency of up to 99.99 % for MS substrates in 3.5 wt.% NaCl solution.
The IL23/Th17 pathway is essential for the onset of inflammatory bowel disease (IBD), yet the specific mechanism by which this pathway initiates the disease remains unknown. In this study, we ...identify the mechanisms that mediate cross-talk between the IL23 pathway and the intestinal barrier in IBD.
The downstream targets of the IL23 pathway were identified by RNA array profiling and confirmed by immunohistochemical staining. The role of miRNAs that interact with IL23 was explored in mice with TNBS-induced colitis. Claudin-8 (CLDN8), a multigene family protein that constitutes the backbone of tight junctions, was identified as a novel target of IL23 in IBD. CLDN8 was significantly downregulated in IBD patients with inflamed colonic mucosa, and in trinitrobenzene sulphonic acid (TNBS) induced colitis in mice. Therapeutic treatment of colitis in mice using an IL23 antibody restored CLDN8 abundance, in parallel with recovery from colitis. In addition, we identify miR-223 as a novel mediator of the crosstalk between the IL23 signal pathway and CLDN8 in the development of IBD. MiR-223 was upregulated in IBD, and its activity was regulated through the IL23 pathway. Antagomir inhibition of miR-223 reactivated CLDN8 and improved a number of signs associated with TNBS-induced colitis in mice.
Our study characterizes a new mechanistic pathway in IBD, in which miR-223 interacts with the IL23 pathway by targeting CLDN8. Strategies designed to disrupt this interaction may provide novel therapeutic agents for the management of IBD.
Superhydrophobic silica films were deposited onto mild steel substrate for the purpose of corrosion protection. The superhydrophobicity was obtained by one-step electrodeposition of inorganic/organic ...hybrid sol–gel films from tetraethoxysilane and dodecyltriethoxysilane mixed sol–gel precursors, as a result of simultaneous generation of high roughness and low-energy surface. The corrosion performance was investigated by monitoring the change of water contact angle, by the electrochemical impedance spectroscopy measurements and by iron dissolution test over the whole immersion time. The results show that the superhydrophobic film provides an effective barrier coating for the mild steel interface.
Ezh2 (Enhancer of zeste homolog 2) protein is the enzymatic component of the Polycomb repressive complex 2 (PRC2), which represses gene expression by methylating lysine 27 of histone H3 (H3K27) and ...regulates cell proliferation and differentiation during embryonic development. Recently, hot-spot mutations of Ezh2 were identified in diffused large B-cell lymphomas and follicular lymphomas. To investigate if tumor growth is dependent on the enzymatic activity of Ezh2, we developed a potent and selective small molecule inhibitor, EI1, which inhibits the enzymatic activity of Ezh2 through direct binding to the enzyme and competing with the methyl group donor S-Adenosyl methionine. EI1-treated cells exhibit genome-wide loss of H3K27 methylation and activation of PRC2 target genes. Furthermore, inhibition of Ezh2 by EI1 in diffused large B-cell lymphomas cells carrying the Y641 mutations results in decreased proliferation, cell cycle arrest, and apoptosis. These results provide strong validation of Ezh2 as a potential therapeutic target for the treatment of cancer.
In this study, a highly sensitive and self‐driven near‐infrared (NIR) light photodetector based on PdSe2/pyramid Si heterojunction arrays, which are fabricated through simple selenization of ...predeposited Pd nanofilm on black Si, is demonstrated. The as‐fabricated hybrid device exhibits excellent photoresponse performance in terms of a large on/off ratio of 1.6 × 105, a responsivity of 456 mA W−1, and a high specific detectivity of up to 9.97 × 1013 Jones under 980 nm illumination at zero bias. Such a relatively high sensitivity can be ascribed to the light trapping effect of the pyramid microstructure, which is confirmed by numerical modeling based on finite‐difference time domain. On the other hand, thanks to the broad optical absorption properties of PdSe2, the as‐fabricated device also exhibits obvious sensitivity to other NIR illuminations with wavelengths of 1300, 1550, and 1650 nm, which is beyond the photoresponse range of Si‐based devices. It is also found that the PdSe2/pyramid Si heterojunction device can also function as an NIR light sensor, which can readily record both “tree” and “house” images produced by 980 and 1300 nm illumination, respectively.
A highly sensitive near‐infrared light photodetector based on PdSe2/pyramid Si heterojunction arrays is developed. The as‐fabricated hybrid device exhibits excellent photoresponse performance in terms of a large on/off ratio of 1.6 × 105, a responsivity of 456 mA W−1, and a high specific detectivity of up to 9.97 × 1013 Jones under 980 nm illumination at zero bias.
The aberrantly upregulated Friend leukemia virus integration 1 (
) is closely correlated with the malignant phenotype of small cell lung cancer (SCLC). It is interesting to note that the CRISPR gene ...knockout by Cas9 gRNAs that target the
coding region and the posttranscriptional knockdown by shRNAs that target the 3' region of
mRNA yielded distinct antimetastasis effects in SCLC cells. This study attempts to examine if
exonic circular RNAs (FECR) function as a new malignant driver that determines the metastatic phenotype in SCLC.
The clinical relevance of FECRs was examined in 56 primary SCLC tissues and 50 non-small cell lung cancer (NSCLC) tissues. The prognostic value of FECRs was examined by measuring serum exosomal FECRs in a longitudinal cohort of patients with SCLC. The oncogenic activity of FECRs was investigated in both SCLC cell lines and animal xenograft studies. Finally, we explored the molecular mechanisms underlying these noncoding RNAs as a malignant driver.
Therapeutic comparison of CRISPR Cas9 knockout and shRNA knockdown of
identified FECRs as a new noncanonical malignant driver in SCLC. Using RNA FISH and quantitative PCR, we found that FECR1 (exons 4-2-3) and FECR2 (exons 5-2-3-4) were aberrantly upregulated in SCLC tissues (
< 0.0001), and was positively associated with lymph node metastasis (
< 0.01). Notably, serum exosomal FECR1 was associated with poor survival (
= 0.038) and clinical response to chemotherapy. Silencing of FECRs significantly inhibited the migration in two highly aggressive SCLC cell lines and reduced tumor metastasis
. Mechanistically, we uncovered that FECRs sequestered and subsequently inactivated tumor suppressor miR584-3p, leading to the activation of the Rho Associated Coiled-Coil Containing Protein Kinase 1 gene (ROCK1).
This study identifies
exonic circular RNAs as a new oncogenic driver that promotes tumor metastasis through the miR584-ROCK1 pathway. Importantly, serum exosomal FECR1 may serve as a promising biomarker to track disease progression of SCLC.
Rice （Oryza safiva L.） is highly susceptible to the rhizosphere salinity than other cereals. High sensitivity has been ob- served, mainly at vegetative and reproductive stages in rice. It is the duty ...of plant physiologists to comprehend the growth, development, and physiological processes of rice plants under stress. This paper includes the overview of rice growth and developmental processes influenced by salt stress and the regulation pathways involved in these processes. It also includes the promising salt tolerance strategies, i.e., genetic modification techniques, agronomic practices to improve rice growth, yield; and role of phytohormones and their management, especially inhibition of ethylene biosynthesis by using inhibitors 1-methylcyclopropene （1-MCP）. Rice cultivation may be a first choice for improvement of salt tolerance through plant growth regulators and improved cultivation techniques. This study will significantly improve the understanding toward low rice grain yield and poor rice resistance under salt stress and will also stream scientific knowledge for effective utilization of salt affected soils by using different regulating ways.
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