Targeting oncogenic miR-335 inhibits growth and invasion of malignant astrocytoma cells

<p>Abstract</p> <p>Background</p> <p>Astrocytomas are the most common and aggressive brain tumors characterized by their highly invasive growth. Gain of chromosome 7 with a hot spot at 7q32 appears to be the most prominent aberration in astrocytoma. Previously reports have shown that microRNA-335 (miR-335) resided on chromosome 7q32 is deregulated in many cancers; however, the biological function of miR-335 in astrocytoma has yet to be elucidated.</p> <p>Results</p> <p>We report that miR-335 acts as a tumor promoter in conferring tumorigenic features such as growth and invasion on malignant astrocytoma. The miR-335 level is highly elevated in C6 astrocytoma cells and human malignant astrocytomas. Ectopic expression of miR-335 in C6 cells dramatically enhances cell viability, colony-forming ability and invasiveness. Conversely, delivery of antagonist specific for miR-335 (antagomir-335) to C6 cells results in growth arrest, cell apoptosis, invasion repression and marked regression of astrocytoma xenografts. Further investigation reveals that miR-335 targets disheveled-associated activator of morphogenesis 1(Daam1) at posttranscriptional level. Moreover, silencing of endogenous Daam1 (siDaam1) could mimic the oncogenic effects of miR-335 and reverse the growth arrest, proapoptotic and invasion repression effects induced by antagomir-335. Notably, the oncogenic effects of miR-335 and siDAAM1 together with anti-tumor effects of antagomir-335 are also confirmed in human astrocytoma U87-MG cells.</p> <p>Conclusion</p> <p>These findings suggest an oncogenic role of miR-335 and shed new lights on the therapy of malignant astrocytomas by targeting miR-335.</p

Brain network mechanism on cognitive control task in the elderly with brain aging: A functional near infrared spectroscopy study

ObjectiveTo study the brain network mechanism of cognitive control in the elderly with brain aging.Materials and methods21 normal young people and 20 elderly people were included in this study. Mini-mental State Examination and functional near-infrared spectroscopy (fNIRS) synchronous judgment test (including forward tests and reverse judgment tests) were performed on all subjects. To observe and compare differences in brain region activation and brain functional connectivity between subjects and forward and reverse trials by recording functional connectivity (FC) in different task paradigms and calculating bilateral prefrontal and primary motor cortical (PMC) areas.ResultsIn the forward and reverse judgment tests, the reaction time of the elderly group was significantly longer than the young group (P &lt; 0.05), and there was no significant difference in the correct rate. In the homologous regions of interest (ROI) data, the FC of PMC and prefrontal cortex (PFC) in the elderly group was significantly decreased (P &lt; 0.05). In the heterologous ROI data, except for left primary motor cortex (LPMC)-left prefrontal cortex (LPFC), the other PMC and PFC of the elderly group were significantly lower than the young group (P &lt; 0.05) while processing the forward judgment test. However, the heterologous ROI data of LPMC-right prefrontal cortex (RPFC), LPMC-LPFC and RPFC-LPFC in the elderly group were significantly lower than the young group (P &lt; 0.05) while processing the reverse judgment test.ConclusionThe results suggest that brain aging affected degeneration of whole brain function, which reduce the speed of information processing and form a brain network functional connection mode different from that of young people

CircDHRS3 inhibits prostate cancer cell proliferation and metastasis through the circDHRS3/miR-421/MEIS2 axis

Prostate cancer is the most prevalent type of cancer among men worldwide. The importance of circular RNA (circRNA) in prostate cancer and its connection to malignancy has been steadily recognized. circRNA expression was obtained by circRNA sequencing of prostate cancer. circRNA and its function were further analysed. The results were verified by qRT-PCR, RIP assay, FISH, RNA pulldown, WB, CCK-8, colony formation assay and wound-healing assay. BALB/c Nude mice were used for xenograft hosts. Low expression of circDHRS3 was assessed in prostate cancer. Overexpression of circDHRS3 inhibited prostate cancer growth and migration in vitro. Additionally, miR-421 was shown to be the downstream target of circDHRS3, as shown by fluorescence in situ hybridization and dual-luciferase experiments. The rescue assay results for the PC3 and Du145 cell lines demonstrated that circDHRS3 inhibits prostate cancer cell lines’ ability to proliferate and metastasize by modulating MEIS2 expression through the circDHRS3/miR-421/MEIS2 axis. In vivo investigations confirmed that the overexpression of circDHRS3 could inhibit both the lung and bone metastasis of prostate cancer cells. circDHRS3 has the potential to become a biomarker and a targeted therapeutic site for prostate cancer, particularly in the malignant stage. Our study indicates that circDHRS3 inhibits prostate cancer cell proliferation and metastasis through the circDHRS3/miR-421/MEIS2 axis

Oncopeptide MBOP Encoded by LINC01234 Promotes Colorectal Cancer through MAPK Signaling Pathway

Colorectal cancer (CRC) ranks third in incidence rate and second in mortality rate of malignancy worldwide, and the diagnosis and therapeutics of it remain to be further studied. With the emergence of noncoding RNAs (ncRNAs) and potential peptides derived from ncRNAs across various biological processes, we here aimed to identify a ncRNA-derived peptide possible for revealing the oncogenesis of CRC. Through combined predictive analysis of the coding potential of a batch of long noncoding RNAs (lncRNAs), the existence of an 85 amino-acid-peptide, named MEK1-binding oncopeptide (MBOP) and encoded from LINC01234 was confirmed. Mass spectrometry and Western blot assays indicated the overexpression of MBOP in CRC tissues and cell lines compared to adjacent noncancerous tissues and the normal colonic epithelial cell line. In vivo and in vitro migration and proliferation assays defined MBOP as an oncogenic peptide. Immunoprecipitation trials showed that MEK1 was the key interacting protein of MBOP, and MBOP promoted the MEK1/pERK/MMP2/MMP9 axis in CRC. Two E3-ligase enzymes MAEA and RMND5A mediated the ubiquitin&ndash;protease-system-related degradation of MBOP. This study indicates that MBOP might be a candidate prognostic indicator and a potential target for clinical therapy of CRC

Identification of new aptamer BC-3 targeting RPS7 from rapid screening for bladder carcinoma

Aptamers, short single DNA or RNA oligonucleotides, have shown immense application potential as molecular probes for the early diagnosis and therapy of cancer. However, conventional cell-SELEX technologies for aptamer discovery are time-consuming and laborious. Here we discovered a new aptamer BC-3 by using an improved rapid X-Aptamer selection process for human bladder carcinoma, for which there is no specific molecular probe yet. We show that BC-3 exhibited excellent affinity in bladder cancer cells but not normal cells. We demonstrate that BC-3 displayed high selectivity for tumor cells over their normal counterparts in vitro, in mice, and in patient tumor tissue specimens. Further endocytosis pathway analysis revealed that BC-3 internalized into bladder cancer cells via clathrin-mediated endocytosis. Importantly, we identified ribosomal protein S7 (RPS7) as the binding target of BC-3 via an integrated methodology (mass spectrometry, colocalization assay, and immunoblotting). Together, we report that a novel aptamer BC-3 is discovered for bladder cancer and its properties in the disease are unearthed. Our findings will facilitate the discovery of novel diagnostic and therapeutic strategies for bladder cancer

Methionine orchestrates the metabolism vulnerability in cisplatin resistant bladder cancer microenvironment

Abstract Metabolism vulnerability of cisplatin resistance in BCa cells remains to be discovered, which we applied integrated multi-omics analysis to elucidate the metabolism related regulation mechanism in bladder cancer (BCa) microenvironment. Integrated multi-omics analysis of metabolomics and proteomics revealed that MAT2A regulated methionine metabolism contributes to cisplatin resistance in BCa cells. We further validated MAT2A and cancer stem cell markers were up-regulated and circARHGAP10 was down-regulated through the regulation of MAT2A protein stability in cisplatin resistant BCa cells. circARHGAP10 formed a complex with MAT2A and TRIM25 to accelerate the degradation of MAT2A through ubiquitin-proteasome pathway. Knockdown of MAT2A through overexpression of circARHGAP10 and restriction of methionine up-take was sufficient to overcome cisplatin resistance in vivo in immuno-deficiency model but not in immuno-competent model. Tumor-infiltrating CD8+ T cells characterized an exhausted phenotype in tumors with low methionine. High expression of SLC7A6 in BCa negatively correlated with expression of CD8. Synergistic inhibition of MAT2A and SLC7A6 could overcome cisplatin resistance in immuno-competent model in vivo. Cisplatin resistant BCa cells rely on methionine for survival and stem cell renewal. circARHGAP10/TRIM25/MAT2A regulation pathway plays an important role in cisplatin resistant BCa cells while circARHGAP10 and SLC7A6 should be evaluated as one of the therapeutic target of cisplatin resistant BCa

ET White Paper: To Find the First Earth 2.0

We propose to develop a wide-field and ultra-high-precision photometric survey mission, temporarily named "Earth 2.0 (ET)". This mission is designed to measure, for the first time, the occurrence rate and the orbital distributions of Earth-sized planets. ET consists of seven 30cm telescopes, to be launched to the Earth-Sun's L2 point. Six of these are transit telescopes with a field of view of 500 square degrees. Staring in the direction that encompasses the original Kepler field for four continuous years, this monitoring will return tens of thousands of transiting planets, including the elusive Earth twins orbiting solar-type stars. The seventh telescope is a 30cm microlensing telescope that will monitor an area of 4 square degrees toward the galactic bulge. This, combined with simultaneous ground-based KMTNet observations, will measure masses for hundreds of long-period and free-floating planets. Together, the transit and the microlensing telescopes will revolutionize our understandings of terrestrial planets across a large swath of orbital distances and free space. In addition, the survey data will also facilitate studies in the fields of asteroseismology, Galactic archeology, time-domain sciences, and black holes in binaries.Comment: 116 pages,79 figure