scholarly journals Structural differences between pri-miRNA paralogs promotes alternative Drosha cleavage and expands target repertoires

2018 ◽  
Author(s):  
Xavier Bofill-De Ros ◽  
Wojciech K. Kasprzak ◽  
Yuba Bhandari ◽  
Lixin Fan ◽  
Quinn Cavanaugh ◽  
...  
Keyword(s):  
Mirna Target ◽  
Downstream Processing ◽  
Mirna Sequence ◽  
Low Grade ◽  
Seed Sequence ◽  
Glioma Patient ◽  
Structural Differences ◽  
Flexible Stem ◽  
Stem Structure ◽  
Distinct Role

AbstractMicroRNA (miRNA) processing begins with Drosha cleavage, the fidelity of which is critical for downstream processing and mature miRNA target specificity. To understand how pri-miRNA sequence and structure influence Drosha cleavage, we studied the maturation of three pri-miR-9 paralogs, which encode the same mature miRNA but differ in the surrounding scaffold. We show that pri-miR-9-1 has a unique Drosha cleavage profile due to its distorted and flexible stem structure. Cleavage of pri-miR-9-1, but not pri-miR-9-2 or pri-miR-9-3, generates an alternative-miR-9 with a shifted seed sequence that expands the scope of its target RNAs. Analyses of low grade glioma patient samples indicate that the alternative-miR-9 plays a distinct role in preventing tumor progression. To generalize our model, we provide evidence that distortion of pri-miRNA stems correlates with Drosha cleavage at non-canonical sites. Our studies reveal that pri-miRNA paralogs can have distinct functions via differential Drosha processing.

scholarly journals Dual miRNases for Triple Incision of miRNA Target: Design Concept and Catalytic Performance

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2459
Author(s):  
Olga Patutina ◽  
Daria Chiglintseva ◽  
Elena Bichenkova ◽  
Svetlana Gaponova ◽  
Nadezhda Mironova ◽  
...  
Keyword(s):  
Mirna Target ◽  
Catalytic Performance ◽  
Rnase H ◽  
Therapeutic Interventions ◽  
Mirna Sequence ◽  
Distinct Advantage ◽  
Rna Sequences ◽  
Ph Optimum ◽  
Additional Advantage ◽  
Recognition Motifs

Irreversible destruction of disease-associated regulatory RNA sequences offers exciting opportunities for safe and powerful therapeutic interventions against human pathophysiology. In 2017, for the first time we introduced miRNAses–miRNA-targeted conjugates of a catalytic peptide and oligonucleotide capable of cleaving an miRNA target. Herein, we report the development of Dual miRNases against oncogenic miR-21, miR-155, miR-17 and miR-18a, each containing the catalytic peptide placed in-between two short miRNA-targeted oligodeoxyribonucleotide recognition motifs. Substitution of adenines with 2-aminoadenines in the sequence of oligonucleotide “shoulders” of the Dual miRNase significantly enhanced the efficiency of hybridization with the miRNA target. It was shown that sequence-specific cleavage of the target by miRNase proceeded metal-independently at pH optimum 5.5–7.5 with an efficiency varying from 15% to 85%, depending on the miRNA sequence. A distinct advantage of the engineered nucleases is their ability to additionally recruit RNase H and cut miRNA at three different locations. Such cleavage proceeds at the central part by Dual miRNase, and at the 5′- and 3′-regions by RNase H, which significantly increases the efficiency of miRNA degradation. Due to increased activity at lowered pH Dual miRNases could provide an additional advantage in acidic tumor conditions and may be considered as efficient tumor-selective RNA-targeted therapeutic.

scholarly journals Single-Institution Experience of Low-Grade Glioma Patient Outcomes Eligible for RTOG 9802

2016 ◽  
Vol 96 (2) ◽  
pp. S90 ◽  
Author(s):  
C.R. Kreofsky ◽  
R.S. Youland ◽  
J.C. Buckner ◽  
J.H. Uhm ◽  
D.H. Lachance ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Glioma Patient ◽  
Single Institution

scholarly journals Radiation protraction schedules for low-grade gliomas: a comparison between different mathematical models

2019 ◽  
Vol 16 (161) ◽  
pp. 20190665
Author(s):  
I. Budia ◽  
A. Alvarez-Arenas ◽  
T. E. Woolley ◽  
G. F. Calvo ◽  
J. Belmonte-Beitia
Keyword(s):  
Tumour Growth ◽  
Therapeutic Strategy ◽  
Clinical Implications ◽  
Time Interval ◽  
Low Grade ◽  
Spatial Effects ◽  
Glioma Patient ◽  
Tumour Control ◽  
Low Grade Gliomas ◽  
Growth Laws

We optimize radiotherapy (RT) administration strategies for treating low-grade gliomas. Specifically, we consider different tumour growth laws, both with and without spatial effects. In each scenario, we find the optimal treatment in the sense of maximizing the overall survival time of a virtual low-grade glioma patient, whose tumour progresses according to the examined growth laws. We discover that an extreme protraction therapeutic strategy, which amounts to substantially extending the time interval between RT sessions, may lead to better tumour control. The clinical implications of our results are also presented.

scholarly journals NQPC-2 Cognitive function of a low-grade glioma patient treated with radiation therapy 28 years ago

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi21-vi22
Author(s):  
Kazuki Yamada ◽  
Makoto Ideguchi ◽  
Masao Matsutani
Keyword(s):  
Radiation Therapy ◽  
Cognitive Function ◽  
Processing Speed ◽  
Social Life ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Small Community ◽  
Glioma Patient ◽  
Who Grade ◽  
Standard Range

Abstract While there are many reports that long-term survivors of low-grade glioma patients treated with radiation therapy cannot lead a healthy social life due to cognitive dysfunction, we report a low-grade glioma patient with almost normal cognitive function even after radiation therapy 28 years ago. CASE REPORT. A 64-year-old woman developed with sudden left hemiparesis and was diagnosed as a small infarction in the left corona radiata. After treated by anticoagulant therapy, she was admitted to our hospital for rehabilitation. Twenty-eight years ago, she underwent surgical resection and radiation therapy with 60 Gy for astrocytoma (WHO grade 2) in the right insular cortex. At the time of this admission, she presented with a good MMSE score of 30 points, but she couldn’t walk and her left hand was less maneuverable. After 109 days of intensive rehabilitation in our hospital, she was discharged on a cane walk, and returned to work as a gas station clerk. COGNITIVE FUNCION. We evaluated her cognitive function on TMT-A/B test, CAT (Clinical Assessment for Attention)and WAIS-4. The TMT test was normal with age adjustments. In CAT, the percentage of correct answers for the 7 constituent items was within the standard range, but in the task of evaluating the required time, a slight delay in processing speed was observed. In WAIS-4, the Full scale IQ was 98 points (normal range) including normal 3 of 4 constituent items. But, only the PSI (processing speed) of 75 point was below the standard range. CONCLUSION: We observed a slight delay in processing speed on her high-level cognitive function tests, but determined that she would be well-adapted to a familiar job in a small community. In fact, she was doing well on the job 10 months after her discharge.

scholarly journals MicroRNA-Guided Processing Impairs Plum Pox Virus Replication, but the Virus Readily Evolves To Escape This Silencing Mechanism

2006 ◽  
Vol 80 (5) ◽  
pp. 2429-2436 ◽  
Author(s):  
Carmen Simón-Mateo ◽  
Juan Antonio García
Keyword(s):  
Rna Silencing ◽  
Host Plants ◽  
Mirna Target ◽  
Mirna Sequence ◽  
Plum Pox Virus ◽  
Virus Infectivity ◽  
Target Sequence ◽  
Silencing Suppressor ◽  
New Type ◽  
Target Sequences

ABSTRACT Since the discovery of microRNA (miRNA)-guided processing, a new type of RNA silencing, the possibility that such a mechanism could play a role in virus defense has been proposed. In this work, we have analyzed whether Plum pox virus (PPV) chimeras bearing miRNA target sequences (miR171, miR167, and miR159), which have been reported to be functional in Arabidopsis, were affected by miRNA function in three different host plants. Some of these PPV chimeras had clearly impaired infectivity compared with those carrying nonfunctional miRNA target sequences. The behaviors of PPV chimeras were similar but not identical in all the plants tested, and the deleterious effect on virus infectivity depended on the miRNA sequence cloned and on the site of insertion in the viral genome. The effect of the miRNA target sequence was drastically alleviated in transgenic plants expressing the silencing suppressor P1/HCPro. Furthermore, we show that virus chimeras readily escape RNA silencing interference through mutations within the miRNA target sequence, which mainly affected nucleotides matching the 5′-terminal region of the miRNA.

Approach to the low-grade glioma patient

2021 ◽  
pp. 136-152
Author(s):  
Carlos G. Romo ◽  
Ananyaa Sivakumar ◽  
Matthias Holdhoff
Keyword(s):  
Low Grade Glioma ◽  
Low Grade ◽  
Glioma Patient

scholarly journals Effects of the ANXA6 polymorphisms on glioma risk and patients prognosis

2019 ◽  
Author(s):  
Tuo Wang ◽  
Yao Sun ◽  
Zichao Xiong ◽  
Jiamin Wu ◽  
Xiaoying Ding ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Cox Regression ◽  
Rank Test ◽  
Low Grade ◽  
Nucleotide Polymorphisms ◽  
Glioma Patient ◽  
Chinese Han ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
Glioma Risk

Abstract BACKGROUND Glioma is the most frequent malignant primary brain tumor, and the outcomes for patients with glioma remain poor. The purpose of this study is to explore the association between ANXA6 polymorphisms and glioma risk as well as the prognosis of glioma patients in the Chinese Han population.METHODS We selected nine single-nucleotide polymorphisms (SNPs) in ANXA6 which were genotyped by Agena MassARRAY from 593 glioma patients and 589 healthy controls. The odds ratio (OR) and 95% confidence interval (CI) were calculated by logistic regression analysis to evaluate the association SNPs with glioma risk. The association between polymorphisms and survival of glioma patient were evaluated using the log-rank test, Kaplan-Meier and Cox regression analysis. RESULTS: Overall analysis found that rs3762993 was significantly associated with an increased glioma risk. Stratification analysis found that rs11960458 was strongly associated with an increased risk of glioma in age >41; rs3762993 was also found to be associated an increased with glioma risk in age >41, ≤41, male and low-grade glioma; but rs4958892 was associated with a decreased risk of glioma in age>41 and male. Interestingly, rs11960458 and rs888988 were correlated with poor prognosis of glioma patient. Furthermore, age, extent of resection and chemotherapy were found to be key prognostic factors in survival of glioma patients.CONCLUSIONS In conclusion, our results indicated that ANXA6 polymorphisms were associated with glioma susceptibility and prognosis. Further studies are required to confirm the results and elucidate the mechanisms of the ANXA6 polymorphisms affect the glioma risk and prognosis.

scholarly journals Functional magnetic resonance imaging of cortical changes in a low-grade glioma patient

2010 ◽  
Vol 67 (11) ◽  
pp. 941-944
Author(s):  
Olivera Sveljo ◽  
Katarina Koprivsek ◽  
Milos Lucic ◽  
Ljubodrag Minic
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Functional Magnetic Resonance Imaging ◽  
Left Hemisphere ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Glioma Patient ◽  
Hemisphere Dominance

Introduction. New methods for studying brain functions have provided the new insights into human brain. It is really possible to study a cortical adaptation in adults who have sustained injury. We reported cortical changes in a left frontal low-grade glioma patient during disease progression and after reoperation by functional magnetic resonance imaging (fMRI). Case report. The use of fMRI exams for localisation of eloquent motor and language areas were performed three times in a period of 15 months: seven years after initial tumor resection, eleven months later and three months after the reoperation. The first fMRI demonstrated cortical activation for motor tasks in the expected location of primary motor area while later examinations showed activations of both primary motor areas for right hand movement. The first exam language evaluation showed the left hemisphere dominance for both language tasks, while the second fMRI demonstrated the right hemisphere dominance for complex word generation task, but the left hemisphere remained dominant in simple language task. After the reoperation, language mapping revealed the left hemisphere dominance for both language tasks. Conclusion. fMRI evaluation of cortical changes in low-grade glioma patients may additionally optimize and individualize neurosurgical treatment.

scholarly journals Cross-Linking Ligation and Sequencing of Hybrids (qCLASH) Reveals an Unpredicted miRNA Targetome in Melanoma Cells

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1096
Author(s):  
Ines Kozar ◽  
Demetra Philippidou ◽  
Christiane Margue ◽  
Lauren A. Gay ◽  
Rolf Renne ◽  
...  
Keyword(s):  
Mirna Target ◽  
Target Genes ◽  
Expression Patterns ◽  
Melanoma Cells ◽  
Mirna Sequence ◽  
Cross Linking ◽  
Aberrant Expression ◽  
Coding Sequence ◽  
Mrna Targets ◽  
Hybrid Molecules

MicroRNAs are key post-transcriptional gene regulators often displaying aberrant expression patterns in cancer. As microRNAs are promising disease-associated biomarkers and modulators of responsiveness to anti-cancer therapies, a solid understanding of their targetome is crucial. Despite enormous research efforts, the success rates of available tools to reliably predict microRNAs (miRNA)-target interactions remains limited. To investigate the disease-associated miRNA targetome, we have applied modified cross-linking ligation and sequencing of hybrids (qCLASH) to BRAF-mutant melanoma cells. The resulting RNA-RNA hybrid molecules provide a comprehensive and unbiased snapshot of direct miRNA-target interactions. The regulatory effects on selected miRNA target genes in predicted vs. non-predicted binding regions was validated by miRNA mimic experiments. Most miRNA–target interactions deviate from the central dogma of miRNA targeting up to 60% interactions occur via non-canonical seed pairing with a strong contribution of the 3′ miRNA sequence, and over 50% display a clear bias towards the coding sequence of mRNAs. miRNAs targeting the coding sequence can directly reduce gene expression (miR-34a/CD68), while the majority of non-canonical miRNA interactions appear to have roles beyond target gene suppression (miR-100/AXL). Additionally, non-mRNA targets of miRNAs (lncRNAs) whose interactions mainly occur via non-canonical binding were identified in melanoma. This first application of CLASH sequencing to cancer cells identified over 8 K distinct miRNA–target interactions in melanoma cells. Our data highlight the importance non-canonical interactions, revealing further layers of complexity of post-transcriptional gene regulation in melanoma, thus expanding the pool of miRNA–target interactions, which have so far been omitted in the cancer field.

Direct Observation of Crystalline Ordering In Naturally Graphitized Carbon Produced by Low Grade Metamorphism

1977 ◽  
Vol 35 ◽  
pp. 162-163
Author(s):  
Thomas R. McKee ◽  
Peter R. Buseck
Keyword(s):  
Crystallite Size ◽  
Sedimentary Rocks ◽  
Carbonaceous Material ◽  
Low Grade ◽  
X Ray ◽  
Graphitized Carbon ◽  
Transmission Electron ◽  
Heat Treated ◽  
Commercial Carbon ◽  
Metamorphic Zone

Sediments commonly contain organic material which appears as refractory carbonaceous material in metamorphosed sedimentary rocks. Grew and others have shown that relative carbon content, crystallite size, X-ray crystallinity and development of well-ordered graphite crystal structure of the carbonaceous material increases with increasing metamorphic grade. The graphitization process is irreversible and appears to be continous from the amorphous to the completely graphitized stage. The most dramatic chemical and crystallographic changes take place within the chlorite metamorphic zone.The detailed X-ray investigation of crystallite size and crystalline ordering is complex and can best be investigated by other means such as high resolution transmission electron microscopy (HRTEM). The natural graphitization series is similar to that for heat-treated commercial carbon blacks, which have been successfully studied by HRTEM (Ban and others).

Sign in / Sign up

Export Citation Format

Share Document