scholarly journals Determination of secondary and tertiary structures of cervical cancer lncRNA diagnostic and siRNA therapeutic biomarkers

2018 ◽  
Vol 23 (1) ◽  
pp. 1 ◽  
Author(s):  
Arli Aditya Parikesit ◽  
Didik Huswo Utomo ◽  
Nihayatul Karimah
Keyword(s):  
Cervical Cancer ◽  
Homo Sapiens ◽  
Interaction Analysis ◽  
3D Structure ◽  
Hpv Infection ◽  
Fine Grained ◽  
Non Coding Rna ◽  
2D Structure ◽  
Conserved Region ◽  
The Stability

Cervical cancer is one of the primary causes of mortality in women due to human papilloma virus (HPV) infection. The fingerprint of an HPV infection could be detected using a long non-coding RNA (lncRNA) biomarker, enabling it to be utilized in molecular diagnostics. The primary structure or sequences of RNA should be annotated within conventional bioinformatics tools. Therefore, this study aimed to determine the fine-grained 2D and 3D structures of lncRNA PVT1 and its respective siRNA inhibitors. lncRNA PVT1 sequences from Homo sapiens, Mus musculus, and Rattus norvegicus were retrieved from Genbank (NCBI). Prediction of the 2D structure and analysis of the interactions of the lncRNA and siRNA were performed using the Vienna RNA package. The 3D structure of the RNA was computed using the SimRNA and ModeRNA software programs. The results showed that lncRNA PVT1 from H. sapiens and M. musculus had a conserved region. However, the lncRNA from both H. sapiens and M. musculus showed a low conserved region, and the 2D structure could not be determined; thus, the annotation and 2D model focused only on H. sapiens. Both of their lncRNA PVT1 also had a short half-life in the cell. Based on the 3D modeling pipeline, the 3D model of lncRNA PVT1 showed the stability and possible function as molecules, while the PVT1 siRNA-lncRNA interaction analysis revealed that the molecules could bind well. Based on these findings, the structures of both lncRNA PVT1 and its siRNA have the potential to be utilized as biomarkers.

scholarly journals Identification of the NADP+ Structural Binding Site and Coenzyme Effect on the Fused G6PD::6PGL Protein from Giardia lamblia

Biomolecules ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 46
Author(s):  
Laura Morales-Luna ◽  
Abigail González-Valdez ◽  
Yudibeth Sixto-López ◽  
José Correa-Basurto ◽  
Beatriz Hernández-Ochoa ◽  
...  
Keyword(s):  
Binding Site ◽  
Giardia Lamblia ◽  
Md Simulation ◽  
Thermal Inactivation ◽  
Homo Sapiens ◽  
3D Structure ◽  
Protozoan Parasite ◽  
Pentose Phosphate ◽  
The Stability ◽  
Glucose 6 Phosphate Dehydrogenase

Giardia lambia is a flagellated protozoan parasite that lives in the small intestine and is the causal agent of giardiasis. It has been reported that G. lamblia exhibits glucose-6-phosphate dehydrogenase (G6PD), the first enzyme in the pentose phosphate pathway (PPP). Our group work demonstrated that the g6pd and 6pgl genes are present in the open frame that gives rise to the fused G6PD::6PGL protein; where the G6PD region is similar to the 3D structure of G6PD in Homo sapiens. The objective of the present work was to show the presence of the structural NADP+ binding site on the fused G6PD::6PGL protein and evaluate the effect of the NADP+ molecule on protein stability using biochemical and computational analysis. A protective effect was observed on the thermal inactivation, thermal stability, and trypsin digestions assays when the protein was incubated with NADP+. By molecular docking, we determined the possible structural-NADP+ binding site, which is located between the Rossmann fold of G6PD and 6PGL. Finally, molecular dynamic (MD) simulation was used to test the stability of this complex; it was determined that the presence of both NADP+ structural and cofactor increased the stability of the enzyme, which is in agreement with our experimental results.

scholarly journals RNAcentral 2021: secondary structure integration, improved sequence search and new member databases

2020 ◽  
Vol 49 (D1) ◽  
pp. D212-D220 ◽  
Author(s):  
◽  
Blake A Sweeney ◽  
Anton I Petrov ◽  
Carlos E Ribas ◽  
Robert D Finn ◽  
...  
Keyword(s):  
Sequence Similarity ◽  
Access Point ◽  
Data Resource ◽  
Structure Information ◽  
Fine Grained ◽  
Sequence Search ◽  
Non Coding Rna ◽  
Wide Range ◽  
Search Tool ◽  
2D Structure

Abstract RNAcentral is a comprehensive database of non-coding RNA (ncRNA) sequences that provides a single access point to 44 RNA resources and >18 million ncRNA sequences from a wide range of organisms and RNA types. RNAcentral now also includes secondary (2D) structure information for >13 million sequences, making RNAcentral the world’s largest RNA 2D structure database. The 2D diagrams are displayed using R2DT, a new 2D structure visualization method that uses consistent, reproducible and recognizable layouts for related RNAs. The sequence similarity search has been updated with a faster interface featuring facets for filtering search results by RNA type, organism, source database or any keyword. This sequence search tool is available as a reusable web component, and has been integrated into several RNAcentral member databases, including Rfam, miRBase and snoDB. To allow for a more fine-grained assignment of RNA types and subtypes, all RNAcentral sequences have been annotated with Sequence Ontology terms. The RNAcentral database continues to grow and provide a central data resource for the RNA community. RNAcentral is freely available at https://rnacentral.org.

scholarly journals R2DT: computational framework for template-based RNA secondary structure visualisation across non-coding RNA types

2020 ◽  
Author(s):  
Blake A. Sweeney ◽  
David Hoksza ◽  
Eric P. Nawrocki ◽  
Carlos Eduardo Ribas ◽  
Fábio Madeira ◽  
...  
Keyword(s):  
Large Subunit ◽  
3D Structure ◽  
Rna Structures ◽  
Computational Framework ◽  
Link Type ◽  
Comprehensive Method ◽  
Non Coding Rna ◽  
Wide Range ◽  
2D Structure ◽  
Non Coding Rnas

AbstractNon-coding RNAs (ncRNA) are essential for all life, and the functions of many ncRNAs depend on their secondary (2D) and tertiary (3D) structure. Despite proliferation of 2D visualisation software, there is a lack of methods for automatically generating 2D representations in consistent, reproducible, and recognisable layouts, making them difficult to construct, compare and analyse. Here we present R2DT, a comprehensive method for visualising a wide range of RNA structures in standardised layouts. R2DT is based on a library of 3,632 templates representing the majority of known structured RNAs, from small RNAs to the large subunit ribosomal RNA. R2DT has been applied to ncRNA sequences from the RNAcentral database and produced >13 million diagrams, creating the world’s largest RNA 2D structure dataset. The software is freely available at https://github.com/rnacentral/R2DT and a web server is found at https://rnacentral.org/r2dt.

scholarly journals The development of novel HPV Drugs by HDAC inhibitor based upon applied bioinformatics tool and their specialized algorithm

2019 ◽  
Vol 9 (5) ◽  
pp. 4428-4432
Keyword(s):  
Cervical Cancer ◽  
Developing Countries ◽  
Drug Design ◽  
Hdac Inhibitor ◽  
Homo Sapiens ◽  
Hdac Inhibitors ◽  
Hpv Infection ◽  
Bioinformatics Tool ◽  
Computational Drug Design ◽  
Novel Drug

The HPV infection, which is the sole cause of cervical cancer, is a malicious threat for developing countries, for instance, Indonesia. Drug for coping HPV infection have been sold in the market namely SAHA or Vorinostat. Mainly, it works by inhibiting the Human Deacetylase Enzyme (HDAC) class II Homo sapiens. However, due to the contradicting report on its efficacy, a novel drug should be developed to remedy the resistance problem. Some groups have successfully developed novel HDAC inhibitors, based upon computational drug design.

A combined ultrastructural and gene molecular research for the relationship between human uterine cervical carcinoma and human papillomavirus

1990 ◽  
Vol 48 (3) ◽  
pp. 204-205
Author(s):  
Kun Lee ◽  
Jingyi Si ◽  
Ricai Han ◽  
Wei Zhang ◽  
Bingbing Tan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Intraepithelial Neoplasia ◽  
Hpv Infection ◽  
Dot Blot ◽  
Homologous Sequences ◽  
Normal Cervical Epithelium ◽  
The Relationship ◽  
Chronic Cervicitis

There are more supports for the view that human papillomavirus (HPV) infection might be an etiological factor in the development of cervical cancer when the association of persistent condylomata is considered. Biopsies from 318 cases with squamous cell carcinoma of uterine cervix, 48 with cervical and vulvar condylomata, 14 with cervical intraepithelial neoplasia (CIN), 34 with chronic cervicitis and 24 normal cervical epithelium were collected from 5 geographic regions of China with different cervical cancer mortalities. All specimens were prepared for Dot blot, Southern blot and in situ DNA-DNA hybridizations by using HPV-11, 16, 18 DNA labelled with 32P and 3H as probes to detect viral homologous sequences in samples. Among them, 32 cases with cervical cancer, 27 with condyloma and 10 normal cervical epitheliums were randomly chosen for comparative EM observation. The results showed that: 1), 192 out of 318 (60.4%) cases of cervical cancer were positive for HPV-16 DNA probe (Table I)

The role of programmed cell death ligand-1/ programmed cell death-1 (PD-L1/PD-1) in HPV-induced cervical cancer and potential for their use in blockade therapy

2020 ◽  
Vol 27 ◽  
Author(s):  
Lifang Zhang ◽  
Yu Zhao ◽  
Quanmei Tu ◽  
Xiangyang Xue ◽  
Xueqiong Zhu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Escape ◽  
Hypoxia Inducible Factor ◽  
Hpv Infection ◽  
Advanced Cervical Cancer ◽  
Cervical Carcinogenesis ◽  
Programmed Cell Death 1

Background: Cervical cancer induced by infection with human papillomavirus (HPV) remains a leading cause of mortality for women worldwide although preventive vaccines and early diagnosis have reduced morbidity and mortality. Advanced cervical cancer can only be treated with either chemotherapy or radiotherapy but outcomes are poor. The median survival for advanced cervical cancer patients is only 16.8 months. Methods: We undertook a structural search of peer-reviewed published studies based on 1). Characteristics of programmed cell death ligand-1/programmed cell death-1(PD-L1/PD-1) expression in cervical cancer and upstream regulatory signals of PD-L1/PD-1 expression, 2). The role of the PD-L1/PD-1 axis in cervical carcinogenesis induced by HPV infection and 3). Whether the PD-L1/PD-1 axis has emerged as a potential target for cervical cancer therapies. Results: One hundred and twenty-six published papers were included in the review, demonstrating that expression of PD-L1/PD-1 is associated with HPV-caused cancer, especially with HPV 16 and 18 which account for approximately 70% of cervical cancer cases. HPV E5/E6/E7 oncogenes activate multiple signaling pathways including PI3K/AKT, MAPK, hypoxia-inducible factor 1α, STAT3/NF-kB and MicroRNAs, which regulate PD-L1/PD-1 axis to promote HPV-induced cervical carcinogenesis. The PD-L1/PD-1 axis plays a crucial role in immune escape of cervical cancer through inhibition of host immune response. creating an "immune-privileged" site for initial viral infection and subsequent adaptive immune resistance, which provides a rationale for therapeutic blockade of this axis in HPV-positive cancers. Currently, Phase I/II clinical trials evaluating the effects of PD-L1/PD-1 targeted therapies are in progress for cervical carcinoma, which provide an important opportunity for the application of anti-PD-L1/anti-PD-1 antibodies in cervical cancer treatment. Conclusion: Recent research developments have led to an entirely new class of drugs using antibodies against the PD-L1/PD-1 thus promoting the body’s immune system to fight the cancer. The expression and roles of the PD-L1/ PD-1 axis in the progression of cervical cancer provide great potential for using PD-L1/PD-1 antibodies as a targeted cancer therapy.

Human Papillomavirus Selected Properties and Related Cervical Cancer Prevention Issues

2020 ◽  
Vol 26 (18) ◽  
pp. 2073-2086
Author(s):  
Saule Balmagambetova ◽  
Andrea Tinelli ◽  
Ospan A. Mynbaev ◽  
Arip Koyshybaev ◽  
Olzhas Urazayev ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Prevention ◽  
Screening Program ◽  
Hpv Infection ◽  
Cervical Cancer Prevention ◽  
Point Of View ◽  
Prevention Strategies ◽  
Middle Income ◽  
Screening Programs

High-risk human papillomavirus strains are widely known to be the causative agents responsible for cervical cancer development. Aggregated damage caused by papillomaviruses solely is estimated in at least 5% of all malignancies of the human body and 16% in cancers that affect the female genital area. Enhanced understanding of the complex issue on how the high extent of carcinogenicity is eventually formed due to the infection by the Papoviridae family would contribute to enhancing current prevention strategies not only towards cervical cancer, but also other HPV associated cancers. This review article is aimed at presenting the key points in two directions: the current cervical cancer prevention and related aspects of HPV behavior. Virtually all applied technologies related to HPV diagnostics and screening programs, such as HPV tests, colposcopy-based tests (VIA/VILI), conventional and liquid-based cytology, currently available are presented. Issues of availability, advantages, and drawbacks of the screening programs, as well as vaccination strategies, are also reviewed in the article based on the analyzed sources. The current point of view regarding HPV is discussed with emphasis on the most problematic aspect of the HPV family concerning the observed increasing number of highly carcinogenic types. Present trends in HPV infection diagnostics throughout the human fluids and tissues are also reported, including the latest novelties in this field, such as HPV assay/self-sample device combinations. Besides, a brief outline of the related prevention issues in Kazakhstan, the leading country of Central Asia, is presented. Kazakhstan, as one of the post-soviet middle-income countries, may serve as an example of the current situation in those terrains, concerning the implementation of globally accepted cervical cancer prevention strategies. Along with positive achievements, such as the development of a nationwide screening program, a range of drawbacks is also analyzed and discussed.

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