scholarly journals Phytochemicals as Modulators of Long Non-Coding RNAs and Inhibitors of Cancer-Related Carbonic Anhydrases

2019 ◽  
Vol 20 (12) ◽  
pp. 2939 ◽  
Author(s):  
Saghafi ◽  
Taheri ◽  
Parkkila ◽  
Emameh
Keyword(s):  
Antisense Rna ◽  
Experimental Studies ◽  
Biological Processes ◽  
Carbonic Anhydrases ◽  
Ca Ix ◽  
Comprehensive Information ◽  
Different Types ◽  
Associated Proteins ◽  
Non Coding Rnas ◽  
Expression Marker

Long non-coding RNAs (lncRNAs) are classified as a group of transcripts which regulate various biological processes, such as RNA processing, epigenetic control, and signaling pathways. According to recent studies, lncRNAs are dysregulated in cancer and play an important role in cancer incidence and spreading. There is also an association between lncRNAs and the overexpression of some tumor-associated proteins, including carbonic anhydrases II, IX, and XII (CA II, CA IX, and CA XII). Therefore, not only CA inhibition, but also lncRNA modulation, could represent an attractive strategy for cancer prevention and therapy. Experimental studies have suggested that herbal compounds regulate the expression of many lncRNAs involved in cancer, such as HOTAIR (HOX transcript antisense RNA), H19, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), PCGEM1 (Prostate cancer gene expression marker 1), PVT1, etc. These plant-derived drugs or phytochemicals include resveratrol, curcumin, genistein, quercetin, epigallocatechin-3-galate, camptothcin, and 3,3′-diindolylmethane. More comprehensive information about lncRNA modulation via phytochemicals would be helpful for the administration of new herbal derivatives in cancer therapy. In this review, we describe the state-of-the-art and potential of phytochemicals as modulators of lncRNAs in different types of cancers.

Structural Alignment of RNAs with Pseudoknots

2011 ◽  
pp. 550-571
Author(s):  
Thomas K. F. Wong ◽  
S. M. Yiu
Keyword(s):  
Secondary Structure ◽  
De Novo ◽  
State Of The Art ◽  
Structural Alignment ◽  
Structural Similarity ◽  
Secondary Structures ◽  
Biological Processes ◽  
Computational Approaches ◽  
Different Types ◽  
Non Coding Rnas

Non-coding RNAs (ncRNAs) are found to be critical for many biological processes. However, identifying these molecules is very difficult and challenging due to the lack of strong detectable signals such as opening read frames. Most computational approaches rely on the observation that the secondary structures of ncRNA molecules are conserved within the same family. Aligning a known ncRNA to a target candidate to determine the sequence and structural similarity helps in identifying de novo ncRNA molecules that are in the same family of the known ncRNA. However, the problem becomes more difficult if the secondary structure contains pseudoknots. Only until recently, many of the existing approaches could not handle structures with pseudoknots. This chapter reviews the state-of-the-art algorithms for different types of structures that contain pseudoknots including standard pseudoknot, simple non-standard pseudoknot, recursive standard pseudoknot, and recursive simple non-standard pseudoknot. Although none of the algorithms is designed for general pseudoknots, these algorithms already cover all known ncRNAs in both Rfam and PseudoBase databases. The evaluation of the algorithms also shows that the approach is useful in identifying ncRNA molecules in other species, which are in the same family of a known ncRNA.

scholarly journals Exosomal Non-coding RNAs-Mediated Crosstalk in the Tumor Microenvironment

2021 ◽  
Vol 9 ◽  
Author(s):  
Qi Chen ◽  
Yuefeng Li ◽  
Yueqin Liu ◽  
Wenlin Xu ◽  
Xiaolan Zhu
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Stromal Cells ◽  
Early Stage ◽  
Circular Rnas ◽  
Biological Processes ◽  
Tumor Cell Growth ◽  
Different Types ◽  
Non Coding Rnas ◽  
Regulatory Functions

Exosomes are secreted by different types of cells in tumor microenvironment (TME) and participate in multiple biological processes of tumors. Non-coding RNAs (ncRNAs) enveloped in exosomes and released to the TME are shown to be involved in tumorigenesis and development, as well as act as important intracellular communication mediators. However, the understanding on the exact regulatory functions and substrates of exosomal RNA is still at an early stage. In this review, we provided an overview on recent studies on exosomes mediating the modulation of both tumor cells and immune cells, then summarized the exosomal ncRNAs [such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)] secreted by tumor cells and stromal cells that exhibited potential capabilities to regulate tumor cell growth, progression, metastasis, drug resistance, and immune response. Our review may hopefully inspire a deeper understanding on the ncRNAs’ function as useful biomarkers for the diagnosis, prognosis, and as novel targets therapy for cancer.

Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

2019 ◽  
Vol 2 (4) ◽  
pp. 83-98 ◽  
Author(s):  
André De Lima Mota ◽  
Bruna Vitorasso Jardim-Perassi ◽  
Tialfi Bergamin De Castro ◽  
Jucimara Colombo ◽  
Nathália Martins Sonehara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucose Metabolism ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Carbonic Anhydrases ◽  
In Vivo Models ◽  
Ca Ix ◽  
Gene And Protein Expression

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression. 

MicroRNAs and their role in hematological malignant diseases

2012 ◽  
Vol 153 (52) ◽  
pp. 2051-2059 ◽  
Author(s):  
Zsuzsanna Gaál ◽  
Éva Oláh
Keyword(s):  
Target Genes ◽  
Lymphoblastic Leukemia ◽  
Cancer Tissue ◽  
Altered Expression ◽  
Diagnosis And Prognosis ◽  
Oncologic Patients ◽  
Different Types ◽  
Non Coding Rnas ◽  
Success Of Treatment ◽  
Posttranscriptional Level

MicroRNAs are a class of small non-coding RNAs regulating gene expression at posttranscriptional level. Their target genes include numerous regulators of cell cycle, cell proliferation as well as apoptosis. Therefore, they are implicated in the initiation and progression of cancer, tissue invasion and metastasis formation as well. MicroRNA profiles supply much information about both the origin and the differentiation state of tumours. MicroRNAs also have a key role during haemopoiesis. An altered expression level of those have often been observed in different types of leukemia. There are successful attempts to apply microRNAs in the diagnosis and prognosis of acute lymphoblastic leukemia and acute myeloid leukemia. Measurement of the expression levels may help to predict the success of treatment with different kinds of chemotherapeutic drugs. MicroRNAs are also regarded as promising therapeutic targets, and can contribute to a more personalized therapeutic approach in haemato-oncologic patients. Orv. Hetil., 2012, 153, 2051–2059.

METHODS FOR SIMULATION OF ACUTE BRAIN ISCHEMIA: PATHOPHYSIOLOGICAL SUBSTANTIATION OF SELECTION AND IMPORTANCE FOR CLINICAL PRACTICE

2019 ◽  
pp. 142-152
Author(s):  
Б.И. Гельцер ◽  
Э.В. Слабенко ◽  
Ю.В. Заяц ◽  
В.Н. Котельников
Keyword(s):  
Clinical Practice ◽  
Experimental Studies ◽  
Cerebrovascular Diseases ◽  
Experimental Models ◽  
Pathological Process ◽  
Ischemic Brain ◽  
Actual Clinical Practice ◽  
Acute Cerebral Ischemia ◽  
Different Types ◽  
Acute Brain Ischemia

Одним из основных требований к разработке экспериментальных моделей цереброваскулярных заболеваний является их максимальная приближенность к реальной клинической практике. В работе систематизированы данные по основным методам моделирования острой ишемии головного мозга (ОИГМ), представлена их классификация, анализируются данные о преимуществах и недостатках той или иной модели. Обсуждаются результаты экспериментальных исследований по изучению патогенеза ОИГМ с использованием различных моделей (полной и неполной глобальной, локальной и мультифокальной ишемии) и способов их реализации (перевязка артерий, клипирование, коагуляция, эмболизация и др.). Особое внимание уделяется «стабильности» последствий острого нарушения мозгового кровообращения: необратимых ишемических повреждений головного мозга или обратимых с реперфузией заданной продолжительности. Отмечается, что важное значение в этих исследованиях должно принадлежать современным методам прижизненной визуализации очагов острого ишемического повреждения, что позволяет оценивать динамику патологического процесса. Предлагаемый метод отвечает требованиям гуманного обращения с животными. Подчеркивается, что выбор релевантной модели ОИГМ определяется задачами предстоящего исследования и технологическими ресурсами научной лаборатории. Development of experimental models for acute forms of cerebrovascular diseases is essential for implementation of methods for their prevention and treatment. One of the principal requirements to such models is their maximum approximation to actual clinical practice. This review systematized major models of acute cerebral ischemia (ACI), their classification, and presented information about their advantages and shortcomings. Also, the review presented results of experimental studies on pathophysiological mechanisms of different types of modeled ACI (complete and incomplete global, local, and multifocal ischemia) and methods for creating these models (arterial ligation, clipping, coagulation, embolization, etc.). Particular attention was paid to “stability” of the consequences of acutely impaired cerebral circulation - an irreversible ischemic brain injury or a reversible injury with reperfusion of a given duration. The authors emphasized that in such studies, a special significance should be given to intravital imaging of acute ischemic damage foci using modern methods, which allow assessing the dynamics of the pathological process and meet the requirements to humane treatment of animals. The choice of a relevant ACI model is determined by objectives of the planned study and the technological resources available at the research laboratory.

LncRNAs a New Target for Post-Stroke Recovery

2020 ◽  
Vol 26 (26) ◽  
pp. 3115-3121
Author(s):  
Jun Yang ◽  
Jingjing Zhao ◽  
Xu Liu ◽  
Ruixia Zhu
Keyword(s):  
Ischemic Stroke ◽  
Microglial Activation ◽  
Vital Role ◽  
Stroke Recovery ◽  
Biological Processes ◽  
Current Development ◽  
Post Stroke ◽  
Cascade Processes ◽  
Non Coding Rnas ◽  
Neuron Injury

LncRNAs (long non-coding RNAs) are endogenous molecules, involved in complicated biological processes. Increasing evidence has shown that lncRNAs play a vital role in the post-stroke pathophysiology. Furthermore, several lncRNAs were reported to mediate ischemia cascade processes include apoptosis, bloodbrain barier breakdown, angiogenesis, microglial activation induced neuroinflammation which can cause neuron injury and influence neuron recovery after ischemic stroke. In our study, we first summarize current development about lncRNAs and post-stroke, focus on the regulatory roles of lncRNAs on pathophysiology after stroke. We also reviewed genetic variation in lncRNA associated with functional outcome after ischemic stroke. Additionally, lncRNA-based therapeutics offer promising strategies to decrease brain damage and promote neurological recovery following ischemic stroke. We believe that lncRNAs will become promising for the frontier strategies for IS and can open up a new path for the treatment of IS in the future.

Abiotic Stress Tolerance in Soybean : Regulated by ncRNA

2016 ◽  
Vol 3 (1) ◽  
Author(s):  
YASIN JESHIMA KHAN ◽  
HUSNARA Tyagi ◽  
Anil kumar Singh ◽  
Santosh kumar. Magadum
Keyword(s):  
Abiotic Stresses ◽  
Target Genes ◽  
Abiotic Stress Tolerance ◽  
Crop Improvement ◽  
Vital Role ◽  
Grain Legume ◽  
Biological Processes ◽  
Small Interfering Rnas ◽  
Cellular Environment ◽  
Non Coding Rnas

Plants respond through a cascade of reactions resulting in varied cellular environment leading to alterations in the patterns of protein expression resulting in phonotypic changes. Single cell genomics and global proteomics came out to be powerful tools and efficient techniques in studying stress tolerant plants. Non-coding RNAs are a distinct class of regulatory RNAs in plants and animals that control a variety of biological processes. Small ncRNAs play a vital role in post transcriptional gene regulation by either translational repression or by inducing mRNA cleavage. The major classes of small RNAs include microRNAs (miRNAs) and small interfering RNAs (siRNAs), which differ in their biogenesis. miRNAs control the expression of cognate target genes by binding to complementary sequences, resulting in cleavage or translational inhibition of the target RNAs. siRNAs too have a similar structure, function, and biogenesis like miRNAs but are derived from long double-stranded RNAs and can often direct DNA methylation at target sequences.In this review, we focus on the involvement of ncRNAs in comabting abiotic stresses of soybean. This review emphasis on previously known miRNAs as they play important role in several abiotic stresses like drought, salinity, chilling and heat stress by their diverse roles in mediating biological processes like gene expression, chromatin formation, defense of genome against invading viruses. This review attempts to elucidate the various kinds of non-coding RNAs explored, their discovery, biogenesis, functions, and response for different type of abiotic stresses and future aspects for crop improvement in the context of soybean, a representative grain legume.

scholarly journals Synthesis, Molecular Docking Analysis and Biological Evaluations of Saccharide-Modified Thiadiazole Sulfonamide Derivatives

2021 ◽  
Vol 22 (11) ◽  
pp. 5482
Author(s):  
Zuo-Peng Zhang ◽  
Ye Zhong ◽  
Zhen-Bin Han ◽  
Lin Zhou ◽  
Hua-Sheng Su ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Human Cancer ◽  
Carbonic Anhydrases ◽  
Inhibitory Effects ◽  
Docking Analysis ◽  
Human Cancer Cell Lines ◽  
Hypoxic Conditions ◽  
Ca Ix ◽  
Topological Polar Surface Area ◽  
Ht 29

A series of saccharide-modified thiadiazole sulfonamide derivatives has been designed and synthesized by the “tail approach” and evaluated for inhibitory activity against carbonic anhydrases II, IX, and XII. Most of the compounds showed high topological polar surface area (TPSA) values and excellent enzyme inhibitory activity. The impacts of some compounds on the viability of HT-29, MDA-MB-231, and MG-63 human cancer cell lines were examined under both normoxic and hypoxic conditions, and they showed certain inhibitory effects on cell viability. Moreover, it was found that the series of compounds had the ability to raise the pH of the tumor cell microenvironment. All the results proved that saccharide-modified thiadiazole sulfonamides have important research prospects for the development of CA IX inhibitors.

scholarly journals Transcriptome analysis reveals potential function of long non-coding RNAs in 20-hydroxyecdysone regulated autophagy in Bombyx mori

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Huili Qiao ◽  
Jingya Wang ◽  
Yuanzhuo Wang ◽  
Juanjuan Yang ◽  
Bofan Wei ◽  
...  
Keyword(s):  
Bombyx Mori ◽  
Target Gene ◽  
Fat Body ◽  
Expression Profiles ◽  
Functional Characterization ◽  
Differentially Expressed ◽  
Post Injection ◽  
Biological Processes ◽  
Potential Target ◽  
Non Coding Rnas

Abstract Background 20-hydroxyecdysone (20E) plays important roles in insect molting and metamorphosis. 20E-induced autophagy has been detected during the larval–pupal transition in different insects. In Bombyx mori, autophagy is induced by 20E in the larval fat body. Long non-coding RNAs (lncRNAs) function in various biological processes in many organisms, including insects. Many lncRNAs have been reported to be potential for autophagy occurrence in mammals, but it has not been investigated in insects. Results RNA libraries from the fat body of B. mori dissected at 2 and 6 h post-injection with 20E were constructed and sequenced, and comprehensive analysis of lncRNAs and mRNAs was performed. A total of 1035 lncRNAs were identified, including 905 lincRNAs and 130 antisense lncRNAs. Compared with mRNAs, lncRNAs had longer transcript length and fewer exons. 132 lncRNAs were found differentially expressed at 2 h post injection, compared with 64 lncRNAs at 6 h post injection. Thirty differentially expressed lncRNAs were common at 2 and 6 h post-injection, and were hypothesized to be associated with the 20E response. Target gene analysis predicted 6493 lncRNA-mRNA cis pairs and 42,797 lncRNA-mRNA trans pairs. The expression profiles of LNC_000560 were highly consistent with its potential target genes, Atg4B, and RNAi of LNC_000560 significantly decreased the expression of LNC_000560 and Atg4B. These results indicated that LNC_000560 was potentially involved in the 20E-induced autophagy of the fat body by regulating Atg4B. Conclusions This study provides the genome-wide identification and functional characterization of lncRNAs associated with 20E-induced autophagy in the fat body of B. mori. LNC_000560 and its potential target gene were identified to be related to 20-regulated autophagy in B. mori. These results will be helpful for further studying the regulatory mechanisms of lncRNAs in autophagy and other biological processes in this insect model.

scholarly journals Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2506
Author(s):  
Wamidh H. Talib ◽  
Ahmad Riyad Alsayed ◽  
Alaa Abuawad ◽  
Safa Daoud ◽  
Asma Ismail Mahmod
Keyword(s):  
Clinical Trials ◽  
Current Knowledge ◽  
Biological Activities ◽  
Experimental Studies ◽  
Therapeutic Effects ◽  
Cell Proliferation Inhibition ◽  
Different Types ◽  
Solid Foundation

Melatonin is a pleotropic molecule with numerous biological activities. Epidemiological and experimental studies have documented that melatonin could inhibit different types of cancer in vitro and in vivo. Results showed the involvement of melatonin in different anticancer mechanisms including apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy, and augmentation of the therapeutic effects of conventional anticancer therapies. Clinical trials revealed that melatonin is an effective adjuvant drug to all conventional therapies. This review summarized melatonin biosynthesis, availability from natural sources, metabolism, bioavailability, anticancer mechanisms of melatonin, its use in clinical trials, and pharmaceutical formulation. Studies discussed in this review will provide a solid foundation for researchers and physicians to design and develop new therapies to treat and prevent cancer using melatonin.

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