scholarly journals MicroRNA Implication in Cancer

2010 ◽  
Vol 2 (1) ◽  
pp. 07-13 ◽  
Author(s):  
Iker BADIOLA
Keyword(s):  
Heart Disease ◽  
Disease Progression ◽  
Human Disease ◽  
Cell Types ◽  
Malignant Cells ◽  
Cancer Disease ◽  
New Class ◽  
Mrna Transcripts ◽  
Cancer Types ◽  
Non Coding Rnas

MicroRNAs (miRNA) are a new class of posttranscriptional regulators. These small non-coding RNAs regulate the expression of target mRNA transcripts and are linked to several human disease such as Alzheimer, cancer or heart disease. But it has been the cancer disease which has experimented the major number of studies of miRNA linked to the disease progression. In the last years it has been reported the deregulation pattern of the miRNAs in malignant cells which have disrupted the control of the proliferation, differentiation or apoptosis. The evidence of the presence of specific miRNA deregulated in concrete cancer types has become the miRNAs like possible biomarkers and therapeutic targets. The specific miRNA patterns deregulated in concrete cancer cell types open new opportunities to the diagnosis and therapy.

scholarly journals The transcriptional hallmarks of intra-tumor heterogeneity across a thousand tumors

2021 ◽  
Author(s):  
Avishai Gavish ◽  
Michael Tyler ◽  
Dor Simkin ◽  
Daniel Kovarsky ◽  
L. Nicolas Gonzalez Castro ◽  
...  
Keyword(s):  
Tumor Heterogeneity ◽  
Cancer Therapeutics ◽  
Cell Types ◽  
Cancer Type ◽  
Malignant Cells ◽  
Cellular Processes ◽  
Narrow View ◽  
Cancer Types ◽  
Context Specific ◽  
Tumor Types

Each tumor contains malignant cells that differ in genotype, phenotype, and in their interactions with the tumor micro-environment (TME). This results in distinct integrated cellular states that govern intra-tumor heterogeneity (ITH), a central challenge of cancer therapeutics. Dozens of recent studies have begun to describe ITH by single cell RNA-seq, but each study typically profiledonly a small number of tumors and provided a narrow view of transcriptional ITH. Here, we curate, annotate and integrate the data from 77 different studies to reveal the patterns of ITH across 1,163 tumor samples covering 24 tumor types. Focusing on the malignant cells, we find thousands of transcriptional ITH programs that can be described by 41 consensus meta-programs (MPs), each consisting of dozens of genes that are coordinately upregulated in subpopulations of cells within many different tumors. The MPs cover diverse cellular processes and differ in their cancer-type distribution. General MPs associated with processes such as cell cycle and stress vary within most tumors, while context-specific MPs reflect the unique biology of particular cancer types, often resembling developmental cell types and suggesting the co-existence of variable differentiation states within tumors. Some of the MPs are further associated with overall tumor proliferation or immune state, highlighting their potential clinical significance. Based on functional similarities among MPs, we propose a set of 11 hallmarks that together account for the majority of observed ITH programs. Given the breadth and scope of the investigated cohort, the MPs and hallmarks described here reflect the first comprehensive pan-cancer description of transcriptional ITH.

scholarly journals Secreted Non-Coding RNAs: Functional Impact on the Tumor Microenvironment and Clinical Relevance in Triple-Negative Breast Cancer

2022 ◽  
Vol 8 (1) ◽  
pp. 5
Author(s):  
Silvia Di Agostino ◽  
Mahrou Vahabi ◽  
Chiara Turco ◽  
Giulia Fontemaggi
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cell Types ◽  
Current Treatment ◽  
High Rate ◽  
Cancer Disease ◽  
Non Coding Rnas ◽  
Therapeutic Tools

Triple-negative breast cancer (TNBC) is a subtype of breast carcinoma characterized by poor prognosis and high rate of metastasis. Current treatment is based on chemo- and/or radiotherapy and surgery. TNBC is devoid of estrogen, progesterone and HER2 receptors. Although precision medicine has come a long way to ameliorate breast cancer disease management, targeted therapies for the treatment of TNBC patients are still limited. Mounting evidence has shown that non-coding RNAs (ncRNAs) drive many oncogenic processes at the basis of increased proliferation, invasion and angiogenesis in TNBC, strongly contributing to tumor progression and resistance to treatments. Many of these ncRNAs are secreted in the tumor microenvironment (TME) and impinge on the activity of the diverse immune and stromal cell types infiltrating the TME. Importantly, secreted ncRNAs may be detected as circulating molecules in serum/plasma from cancer patients and are emerging a promising diagnostic/therapeutic tools in TNBC. This review aims to discuss novel insights about the role of secreted circulating ncRNAs in the intercellular communication in the tumor microenvironment and their potential clinical use as diagnostic and prognostic non-invasive biomarkers in TNBC.

scholarly journals Sirtuin Inhibitors Are Broadly Antiviral against Arboviruses

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Brent A. Hackett ◽  
Mark Dittmar ◽  
Elisha Segrist ◽  
Nathan Pittenger ◽  
Julie To ◽  
...  
Keyword(s):  
High Throughput ◽  
Human Cell ◽  
Human Disease ◽  
Rift Valley Fever Virus ◽  
Cell Types ◽  
Viral Rna ◽  
Early Step ◽  
Valley Fever ◽  
New Class ◽  
Do So

ABSTRACT Arthropod-borne viruses are diverse pathogens and are often associated with human disease. These viruses span multiple genera, including flaviviruses, alphaviruses, and bunyaviruses. In a high-throughput drug screen, we found that tenovin-1 was antiviral against the flaviviruses Zika virus and dengue virus. Tenovin-1 is a sirtuin inhibitor, and here we found that inhibition of sirtuins, but not inhibition of the related histone deacetylases, is potently antiviral against diverse arboviruses. Sirtuin inhibitors block infection of arboviruses in multiple human cell types. We found that sirtuin inhibitors arrest infection downstream of entry but that they do so at an early step, preventing the accumulation of viral RNA and protein. However, sirtuin inhibitors had no impact on the replication of flaviviral replicons, suggesting a defect in the establishment of replication. Consistent with this, we found that sirtuin inhibitors impacted double-stranded RNA (dsRNA) accumulation during flaviviral infection. Since these viruses infect vector insects, we also tested whether sirtuin inhibitors impacted infection of adult flies and found that these inhibitors blocked infection; therefore, they target highly conserved facets of replication. Taken together, these results suggest that sirtuin inhibitors represent a new class of potent host-targeting antivirals. IMPORTANCE Arthropod-borne viruses are diverse pathogens and are associated with human disease. Through high-throughput drug screening, we found that sirtuin inhibitors are potently antiviral against diverse arboviruses, including flaviviruses such as West Nile virus, bunyaviruses such as Rift Valley fever virus, and alphaviruses such as chikungunya virus. Sirtuin inhibitors block infection of these viruses in multiple human cell types. Moreover, we found that sirtuin inhibitors arrest infection downstream of entry but that they do so at an early step, preventing the accumulation of viral RNA and protein. Since these viruses infect vector insects, we also tested whether sirtuin inhibitors impacted infection of adult flies and found that these inhibitors blocked infection; therefore, they target highly conserved facets of replication. Taken together, these results suggest that sirtuin inhibitors represent a new class of potent host-targeting antivirals.

scholarly journals The Emerging Functions of Circular RNAs in Bladder Cancer

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4618
Author(s):  
Kai Sun ◽  
Di Wang ◽  
Burton B. Yang ◽  
Jian Ma
Keyword(s):  
Bladder Cancer ◽  
Chemotherapy Resistance ◽  
Circular Rnas ◽  
Closed Loops ◽  
New Class ◽  
Common Cancer ◽  
High Conservation ◽  
Cancer Types ◽  
Non Coding Rnas ◽  
Diagnostic And Prognostic Value

Bladder cancer (BC) is among the top ten most common cancer types worldwide and is a serious threat to human health. Circular RNAs (circRNAs) are a new class of non-coding RNAs generated by covalently closed loops through back-splicing. As an emerging research hotspot, circRNAs have attracted considerable attention due to their high conservation, stability, abundance, and specificity of tissue development. Accumulating evidence has revealed different form of circRNAs are closely related to the malignant phenotype, prognosis and chemotherapy resistance of BC, suggesting that different circRNAs may be promising biomarkers and have therapeutic significance in BC. The intention of this review is to summarize the mechanisms of circRNA-mediated BC progression and their diagnostic and prognostic value as biomarkers, as well as to further explore their roles in chemotherapy resistance.

scholarly journals Combining Dextran Conjugates with Stimuli-Responsive and Folate-Targeting Activity: A New Class of Multifunctional Nanoparticles for Cancer Therapy

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1108
Author(s):  
Manuela Curcio ◽  
Alessandro Paolì ◽  
Giuseppe Cirillo ◽  
Sebastiano Di Pietro ◽  
Martina Forestiero ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Drug Release ◽  
Metastatic Cancer ◽  
Stimuli Responsive ◽  
Cancer Disease ◽  
New Class ◽  
Self Assembling ◽  
Redox Responsive ◽  
Potential Applicability ◽  
Mean Size

Nanoparticles with active-targeting and stimuli-responsive behavior are a promising class of engineered materials able to recognize the site of cancer disease, targeting the drug release and limiting side effects in the healthy organs. In this work, new dual pH/redox-responsive nanoparticles with affinity for folate receptors were prepared by the combination of two amphiphilic dextran (DEX) derivatives. DEXFA conjugate was obtained by covalent coupling of the polysaccharide with folic acid (FA), whereas DEXssPEGCOOH derived from a reductive amination step of DEX was followed by condensation with polyethylene glycol 600. After self-assembling, nanoparticles with a mean size of 50 nm, able to be destabilized in acidic pH and reducing media, were obtained. Doxorubicin was loaded during the self-assembling process, and the release experiments showed the ability of the proposed system to modulate the drug release in response to different pH and redox conditions. Finally, the viability and uptake experiments on healthy (MCF-10A) and metastatic cancer (MDA-MB-231) cells proved the potential applicability of the proposed system as a new drug vector in cancer therapy.

scholarly journals NF-κB in Cancer Immunity: Friend or Foe?

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 355
Author(s):  
Guilhem Lalle ◽  
Julie Twardowski ◽  
Yenkel Grinberg-Bleyer
Keyword(s):  
Immune Responses ◽  
Therapeutic Potential ◽  
Cell Types ◽  
Transcriptional Activators ◽  
New Class ◽  
Complex Interactions ◽  
Cancer Immunity ◽  
Distinct Cell ◽  
Cancer Initiation ◽  
Cancer Outcome

The emergence of immunotherapies has definitely proven the tight relationship between malignant and immune cells, its impact on cancer outcome and its therapeutic potential. In this context, it is undoubtedly critical to decipher the transcriptional regulation of these complex interactions. Following early observations demonstrating the roles of NF-κB in cancer initiation and progression, a series of studies converge to establish NF-κB as a master regulator of immune responses to cancer. Importantly, NF-κB is a family of transcriptional activators and repressors that can act at different stages of cancer immunity. In this review, we provide an overview of the selective cell-intrinsic contributions of NF-κB to the distinct cell types that compose the tumor immune environment. We also propose a new view of NF-κB targeting drugs as a new class of immunotherapies for cancer.

scholarly journals AB0308 NO SIGNS OF CONGESTIVE HEART DISEASE PROGRESSION IN PATIENTS WITH RHEUMATOID ARTHRITIS ON IL-6 RECEPTOR ANTAGONIST AFTER 12 MONTHS TREATMENT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1452.3-1453
Author(s):  
A. Martynova ◽  
T. Popkova ◽  
H. Gerasimova
Keyword(s):  
Rheumatoid Arthritis ◽  
Heart Disease ◽  
Receptor Antagonist ◽  
Disease Progression ◽  
European Heart Journal ◽  
Heart Function ◽  
Clinical Signs ◽  
Left Ventricular ◽  
Ultrasound Evaluation ◽  
Congestive Heart Disease

Background:N-terminal pro-brain natriuretic peptide (NT-proBNP) is a known marker of heart dysfunction, mainly described in patients with high activity of rheumatoid arthritis (RA). Further knowledge of the influence of the IL-6 receptor antagonist, tocilizumab (TCZ), on NT-proBNP levels and systolic heart function is yet to be obtained.Objectives:Access the effect of 12 months TCZ therapy on NT-proBNP levels, transthoracal ehocardiography results and analyze the association between congestive heart disease progression and RA activity.Methods:37 RA patients (pts) (31F/6M); median age 56,5 [48; 63,5] years; disease duration 48 [6; 348] months; DAS28 score 6,15 [5,44; 6,45]; rheumatoid factor (RF)+100%; anti–citrullinated protein antibody (ACPA) + 79,6% were treated in an open-label study with TCZ (8 mg/kg every 4 weeks). Identification of NT-pro-BNT in blood serum, transthoracal ultrasound evaluation of left ventriculum ejection fraction (LVEF), E/A ratio performed at baseline and 12 months.Results:11 (29,7%) pts had congestive heart disease (CHD) (II functional class of NYHA), 7 (18,9%) pts having signs of mild left ventricular dysfunction (LVD) as dyspnea, shortness of breath, cardiotropic treatment remained the same in the course of the study. After 12 month TCZ treatment as RA activity lowered (DAS28 2.32 [1,75; 3,15], р<0,05), NT-proBNP levels decreased (100,95 [57.9; 117.6] pg/ml to 90,46 [33.62; 106.6] pg/ml), along with elevation of LVEF (60,75 [60; 70]% to 67,68 [62.5; 73.5], p = 0,001). Increase of E/A (0,97 [0.8; 1.17] to 1,04 [0.7; 1.42] correlated with decrease of NT-proBNP level (r = -0,63, p=0,036). Raise of LVEF over 12 months correlated with decrease of RA activity according to SDAI scale (r= -0,670, p<0,05). No significant relationship between NT-proBNP levels, LVEF, E/A and other scales measuring RA activity was found. Clinically all patients had improvement in evaluation of their health and no signs of CHD or RVD progression were found.Conclusion:Use of TCZ in patients with active RA showed none to positive influence on heart condition, specifically, lowering NT-proBNP levels, improving LVEF and reducing clinical signs of LVD.References:[1]Pan Y, Li D, Ma J, Shan L, Wei M. NT-proBNP test with improved accuracy for the diagnosis of chronic heart failure. Medicine (Baltimore). 2017 Dec;96(51):e9181.[2]D Novikova, I Kirillova, E Markelova et al. The first report of significantly improvement of NT-proBNP level in rheumatoid arthritis patients treated with tofacitinib during 12-month follow-up, European Heart Journal, Volume 40, Issue Supplement_1, October 2019, ehz745.0836.[3]Pappas DA, Nyberg F, Kremer JM et al. Clin Rheumatol. 2018 Sep;37(9):2331-2340.Disclosure of Interests:None declared

scholarly journals Long Non-Coding RNAs (lncRNAs) in Cardiovascular Disease Complication of Type 2 Diabetes

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 145
Author(s):  
Nurruzanna Ismail ◽  
Noraidatulakma Abdullah ◽  
Nor Azian Abdul Murad ◽  
Rahman Jamal ◽  
Siti Aishah Sulaiman
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Disease Progression ◽  
Biological Fluids ◽  
Specific Cell ◽  
New Paradigm ◽  
Diagnostic Potential ◽  
Non Coding Rnas

The discovery of non-coding RNAs (ncRNAs) has opened a new paradigm to use ncRNAs as biomarkers to detect disease progression. Long non-coding RNAs (lncRNA) have garnered the most attention due to their specific cell-origin and their existence in biological fluids. Type 2 diabetes patients will develop cardiovascular disease (CVD) complications, and CVD remains the top risk factor for mortality. Understanding the lncRNA roles in T2D and CVD conditions will allow the future use of lncRNAs to detect CVD complications before the symptoms appear. This review aimed to discuss the roles of lncRNAs in T2D and CVD conditions and their diagnostic potential as molecular biomarkers for CVD complications in T2D.

scholarly journals The atlas of RNase H antisense oligonucleotide distribution and activity in the CNS of rodents and non-human primates following central administration

2020 ◽  
Author(s):  
Paymaan Jafar-nejad ◽  
Berit Powers ◽  
Armand Soriano ◽  
Hien Zhao ◽  
Daniel A Norris ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Muscular Atrophy ◽  
Neurological Diseases ◽  
Cell Types ◽  
Rnase H ◽  
Central Administration ◽  
Spinal Motor Neurons ◽  
New Class ◽  
Wide Range ◽  
Therapeutic Development

Abstract Antisense oligonucleotides (ASOs) have emerged as a new class of drugs to treat a wide range of diseases, including neurological indications. Spinraza, an ASO that modulates splicing of SMN2 RNA, has shown profound disease modifying effects in Spinal Muscular Atrophy (SMA) patients, energizing efforts to develop ASOs for other neurological diseases. While SMA specifically affects spinal motor neurons, other neurological diseases affect different central nervous system (CNS) regions, neuronal and non-neuronal cells. Therefore, it is important to characterize ASO distribution and activity in all major CNS structures and cell types to have a better understanding of which neurological diseases are amenable to ASO therapy. Here we present for the first time the atlas of ASO distribution and activity in the CNS of mice, rats, and non-human primates (NHP), species commonly used in preclinical therapeutic development. Following central administration of an ASO to rodents, we observe widespread distribution and target RNA reduction throughout the CNS in neurons, oligodendrocytes, astrocytes and microglia. This is also the case in NHP, despite a larger CNS volume and more complex neuroarchitecture. Our results demonstrate that ASO drugs are well suited for treating a wide range of neurological diseases for which no effective treatments are available.

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