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1.
Molecules ; 29(4)2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38398553

RESUMO

Selenium is a trace and necessary micronutrient for human, animal, and microbial health. Many researchers have recently been interested in selenium nanoparticles (SeNPs) due to their biocompatibility, bioavailability, and low toxicity. As a result of their greater bioactivity, selenium nanoparticles are widely employed in a variety of biological applications. Physical, chemical, and biological approaches can all be used to synthesize selenium nanoparticles. Since it uses non-toxic solvents and operates at a suitable temperature, the biological technique is a preferable option. This review article addresses the processes implemented in the synthesis of SeNPs and highlights their medicinal uses, such as the treatment of fungi, bacteria, cancer, and wounds. Furthermore, we discuss the most recent findings on the potential of several biological materials for selenium nanoparticle production. The precursor, extract, process, time, temperature, and other synthesis criteria will be elaborated in conjunction with the product's physical properties (size, shape, and stability). The synergies of SeNP synthesis via various methods aid future researchers in precisely synthesizing SeNPs and using them in desired applications.


Assuntos
Pesquisa Biomédica , Nanopartículas , Selênio , Oligoelementos , Animais , Humanos , Selênio/química , Nanopartículas/química , Bactérias
2.
Curr Issues Mol Biol ; 45(9): 7257-7274, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37754243

RESUMO

Prostate cancer (PCa) is the leading cancer in men globally. The association between PCa and long non-coding RNAs (lncRNAs) has been reported. Aberrantly expressed lncRNAs have been documented in each of the cancer "hallmarks". Androgen signaling plays an important role in PCa progression. This study aimed to profile the aberrantly expressed lncRNAs in androgen-dependent (LNCaP) PCa compared to androgen-independent (PC-3) PCa cells. This was achieved by using a 384-well plate of PCa lncRNA gene panel. Differential expression of ±2 up or downregulation was determined using the CFX Maestro software v2.1. LncSEA and DIANA-miRPath were used to identify the enriched pathways. Telomerase RNA component (TERC) lncRNA was illustrated to participate in various tumourigenic classes by in silico bioinformatics analysis and was thus selected for validation using RT-qPCR. Further bioinformatics analysis revealed the involvement of differentially expressed lncRNAs in oncogenic pathways. Some lncRNAs undergo hypermethylation, others are encapsulated by exosomes, while others interact with several microRNAs (miRNAs), favouring tumourigenic pathways. Notably, TERC lncRNA was shown to interact with tumour-suppressor miRNAs hsa-miR-4429 and hsa-miR-320b. This interaction in turn activates TGF-ß-signaling and ECM-receptor interaction pathways, favouring the progression of PCa. Understanding lncRNAs as competitive endogenous RNA molecules and their interactions with miRNAs may aid in the identification of novel prognostic PCa biomarkers and therapeutic targets.

3.
Molecules ; 28(16)2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37630236

RESUMO

Cancer is a global health concern with rising incidence, morbidity, and mortality. The interaction between the tumor and immune cells within the tumor microenvironment is facilitated by signaling pathways driven by immunomodulatory proteins. Alternative splicing regulates the production of multiple immunomodulatory proteins with diverse functionality from a single mRNA transcript. Splicing factors are pivotal in modulating alternative splicing processes but are also subject to regulation. The dysregulation of alternative splicing may result from splicing factor (SF) abnormal expression levels and mutations in the cis and trans-acting elements and small nuclear RNA (snRNA) molecules. Aberrant splicing may generate abnormal mRNA transcripts encoding isoforms with altered functions that contribute to tumorigenesis or cancer progression. This review uncovers the complexity of immunomodulatory genes splicing dysregulation in oncogenesis. Identifying specific immunomodulatory splicing isoforms that contribute to cancer could be utilized to improve current immunotherapeutic drugs or develop novel therapeutic interventions for cancer.


Assuntos
Carcinogênese , Transformação Celular Neoplásica , Humanos , Carcinogênese/genética , Transformação Celular Neoplásica/genética , Engenharia Genética , Processamento Alternativo/genética , RNA Mensageiro , Microambiente Tumoral/genética
4.
Int J Mol Sci ; 23(2)2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-35054814

RESUMO

Precision oncology can be defined as molecular profiling of tumors to identify targetable alterations. Emerging research reports the high mortality rates associated with type II endometrial cancer in black women and with prostate cancer in men of African ancestry. The lack of adequate genetic reference information from the African genome is one of the major obstacles in exploring the benefits of precision oncology in the African context. Whilst external factors such as the geography, environment, health-care access and socio-economic status may contribute greatly towards the disparities observed in type II endometrial and prostate cancers in black populations compared to Caucasians, the contribution of African ancestry to the contribution of genetics to the etiology of these cancers cannot be ignored. Non-coding RNAs (ncRNAs) continue to emerge as important regulators of gene expression and the key molecular pathways involved in tumorigenesis. Particular attention is focused on activated/repressed genes and associated pathways, while the redundant pathways (pathways that have the same outcome or activate the same downstream effectors) are often ignored. However, comprehensive evidence to understand the relationship between type II endometrial cancer, prostate cancer and African ancestry remains poorly understood. The sub-Saharan African (SSA) region has both the highest incidence and mortality of both type II endometrial and prostate cancers. Understanding how the entire transcriptomic landscape of these two reproductive cancers is regulated by ncRNAs in an African cohort may help elucidate the relationship between race and pathological disparities of these two diseases. This review focuses on global disparities in medicine, PCa and ECa. The role of precision oncology in PCa and ECa in the African population will also be discussed.


Assuntos
Negro ou Afro-Americano/genética , Neoplasias do Endométrio/genética , Genômica , Disparidades nos Níveis de Saúde , Medicina de Precisão , Neoplasias da Próstata/genética , Feminino , Humanos , Masculino
5.
Int J Mol Sci ; 23(22)2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36430229

RESUMO

Gastric cancer (GC) is one of the major causes of cancer deaths worldwide. The disease is seldomly detected early and this limits treatment options. Because of its heterogeneous and complex nature, the disease remains poorly understood. The literature supports the contribution of the gut microbiome in the carcinogenesis and chemoresistance of GC. Drug resistance is the major challenge in GC therapy, occurring as a result of rewired metabolism. Metabolic rewiring stems from recurring genetic and epigenetic factors affecting cell development. The gut microbiome consists of pathogens such as H. pylori, which can foster both epigenetic alterations and mutagenesis on the host genome. Most of the bacteria implicated in GC development are Gram-negative, which makes it challenging to eradicate the disease. Gram-negative bacterium co-infections with viruses such as EBV are known as risk factors for GC. In this review, we discuss the role of microbiome-induced GC carcinogenesis. The disease risk factors associated with the presence of microorganisms and microbial dysbiosis are also discussed. In doing so, we aim to emphasize the critical role of the microbiome on cancer pathological phenotypes, and how microbiomics could serve as a potential breakthrough in determining effective GC therapeutic targets. Additionally, consideration of microbial dysbiosis in the GC classification system might aid in diagnosis and treatment decision-making, taking the specific pathogen/s involved into account.


Assuntos
Helicobacter pylori , Microbiota , Neoplasias Gástricas , Humanos , Metagenômica , Disbiose/microbiologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia , Epigenômica , Recidiva Local de Neoplasia , Microbiota/genética , Helicobacter pylori/genética , Carcinogênese/patologia
6.
Int J Mol Sci ; 23(16)2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-36012262

RESUMO

Malignant mesotheliomas (MM) are hard to treat malignancies with poor prognosis and high mortality rates. This cancer is highly misdiagnosed in Sub-Saharan African countries. According to literature, the incidence of MM is likely to increase particularly in low-middle-income countries (LMICs). The burden of asbestos-induced diseases was estimated to be about 231,000 per annum. Lack of awareness and implementation of regulatory frameworks to control exposure to asbestos fibers contributes to the expected increase. Exposure to asbestos fibers can lead to cancer initiation by several mechanisms. Asbestos-induced epigenetic modifications of gene expression machinery and non-coding RNAs promote cancer initiation and progression. Furthermore, microbiome-epigenetic interactions control the innate and adaptive immunity causing exacerbation of cancer progression and therapeutic resistance. This review discusses epigenetic mechanisms with more focus on miRNAs and their interaction with the microbiome. The potential use of epigenetic alterations and microbiota as specific biomarkers to aid in the early detection and/or development of therapeutic targets is explored. The advancement of combinatorial therapies to prolong overall patient survival or possible eradication of MM especially if it is detected early is discussed.


Assuntos
Amianto , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Microbiota , Amianto/efeitos adversos , Epigenômica , Humanos , Imunidade , Neoplasias Pulmonares/genética , Mesotelioma/etiologia
7.
Int J Mol Sci ; 22(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34360891

RESUMO

Globally, HIV/AIDS and cancer are increasingly public health problems and continue to exist as comorbidities. The sub-Saharan African region has the largest number of HIV infections. Malignancies previously associated with HIV/AIDS, also known as the AIDS-defining cancers (ADCs) have been documented to decrease, while the non-AIDS defining cancer (NADCs) are on the rise. On the other hand, cancer is a highly heterogeneous disease and precision oncology as the most effective cancer therapy is gaining attraction. Among HIV-infected individuals, the increased risk for developing cancer is due to the immune system of the patient being suppressed, frequent coinfection with oncogenic viruses and an increase in risky behavior such as poor lifestyle. The core of personalised medicine for cancer depends on the discovery and the development of biomarkers. Biomarkers are specific and highly sensitive markers that reveal information that aid in leading to the diagnosis, prognosis and therapy of the disease. This review focuses mainly on the risk assessment, diagnostic, prognostic and therapeutic role of various cancer biomarkers in HIV-positive patients. A careful selection of sensitive and specific HIV-associated cancer biomarkers is required to identify patients at most risk of tumour development, thus improving the diagnosis and prognosis of the disease.


Assuntos
Síndrome da Imunodeficiência Adquirida/diagnóstico , Síndrome da Imunodeficiência Adquirida/epidemiologia , HIV-1 , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/virologia , Terapia Antirretroviral de Alta Atividade/métodos , Biomarcadores Tumorais/classificação , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Comorbidade , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Neoplasias/genética , Neoplasias/metabolismo , Vírus Oncogênicos , Medicina de Precisão/métodos , Prevalência , Prognóstico , Medição de Risco , Fatores de Risco , Resultado do Tratamento
8.
Int J Mol Sci ; 22(18)2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34576278

RESUMO

Cervical cancer is a public health problem and has devastating effects in low-to-middle-income countries (LTMICs) such as the sub-Saharan African (SSA) countries. Infection by the human papillomavirus (HPV) is the main cause of cervical cancer. HIV positive women have higher HPV prevalence and cervical cancer incidence than their HIV negative counterparts do. Concurrent HPV/HIV infection is catastrophic, particularly to African women due to the high prevalence of HIV infections. Although various studies show a relationship between HPV, HIV and cervical cancer, there is still a gap in the knowledge concerning the precise nature of this tripartite association. Firstly, most studies show the relationship between HPV and cervical cancer at genomic and epigenetic levels, while the transcriptomic landscape of this relationship remains to be elucidated. Even though many studies have shown HPV/HIV dual viral pathogenesis, the dual molecular oncoviral effects on the development of cervical cancer remains largely uncertain. Furthermore, the effect of highly active antiretroviral therapy (HAART) on the cellular splicing machinery is unclear. Emerging evidence indicates the vital role played by host splicing events in both HPV and HIV infection in the development and progression to cervical cancer. Therefore, decoding the transcriptome landscape of this tripartite relationship holds promising therapeutic potential. This review will focus on the link between cellular splicing machinery, HPV, HIV infection and the aberrant alternative splicing events that take place in HIV/HPV-associated cervical cancer. Finally, we will investigate how these aberrant splicing events can be targeted for the development of new therapeutic strategies against HPV/HIV-associated cervical cancer.


Assuntos
Infecções por HIV/complicações , HIV-1/genética , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/virologia , Processamento Alternativo , Terapia Antirretroviral de Alta Atividade , Dano ao DNA , Feminino , Geografia , Humanos , Incidência , RNA Mensageiro/metabolismo , Retroviridae , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Displasia do Colo do Útero/complicações , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia
9.
Anticancer Drugs ; 30(8): 767-773, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31274515

RESUMO

Retinoblastoma binding protein 6 (RBBP6) is a cancer-related protein that has been implicated in the regulation of cell cycle and apoptosis. RBBP6 isoform 1 has been demonstrated to interact with two tumour suppressors, p53 and pRB. Isoform 1 been shown to regulate p53 through its ubiquitin ligase activity, thus implicating in cell cycle regulation and apoptosis. Isoforms 1 and 2 are multidomain proteins containing a domain with no name (DWNN) domain, a Zinc Finger, a RING Finger, an Rb-binding domain and a p53-binding domain. The RBBP6 isoform 3 comprises the DWNN domain only. Isoform 4 lacks the Rb-binding domain but its role is less understood. RBBP6 isoform 3 has been reported as a cell cycle regulator with anticancer potential. There have been several studies that have clearly demonstrated that RBBP6 may be an important biomarker for cancer diagnosis and a potential drug target for cancer treatment. This work focused on differential expression of RBBP6 transcripts in different cancers, providing detailed analysis of their potential as diagnostic biomarkers for different cancers. These cancers include breast, liver, cervical and colon carcinomas. The expression of RBBP6 transcripts may further provide better understanding of the role of the RBBP6 in carcinogenesis and cell homeostasis.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Ligação a DNA/metabolismo , Terapia de Alvo Molecular , Neoplasias/diagnóstico , Neoplasias/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Humanos , Neoplasias/terapia , Prognóstico
10.
Int J Mol Sci ; 19(8)2018 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-30044440

RESUMO

TSPO is a receptor involved in the regulation of cellular proliferation, apoptosis and mitochondrial functions. Previous studies showed that the expression of TSPO protein correlated positively with tumour malignancy and negatively with patient survival. The aim of this study was to determine the transcription of Tspo mRNA in various types of normal and cancer tissues. In situ hybridization was performed to localise the Tspo mRNA in various human normal and cancer tissues. The relative level of Tspo mRNA was quantified using fluorescent intensity and visual estimation of colorimetric staining. RT-PCR was used to confirm these mRNA levels in normal lung, lung cancer, liver cancer, and cervical cancer cell lines. There was a significant increase in the level of transcription in liver, prostate, kidney, and brain cancers while a significant decrease was observed in cancers of the colon and lung. Quantitative RT-PCR confirmed that the mRNA levels of Tspo are higher in a normal lung cell line than in a lung cancer cell line. An increase in the expression levels of Tspo mRNA is not necessarily a good diagnostic biomarker in most cancers with changes not being large enough to be significantly different when detected by in situ hybridisation.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias/diagnóstico , Neoplasias/metabolismo , Receptores de GABA/metabolismo , Células A549 , Análise de Variância , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Feminino , Células HEK293 , Células HeLa , Células Hep G2 , Humanos , Ligantes , Masculino , Neoplasias/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de GABA/genética
11.
Exp Mol Pathol ; 103(2): 121-134, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28797846

RESUMO

Cancer is a leading cause of mortality and morbidity worldwide and second only to cardiovascular diseases. Cancer is a challenge in African countries because generally there is limited funding available to deal with the cancer epidemic and awareness and this should be prioritised and all possible resources should be utilized to prevent and treat cancer. The current review reports on the role of African medicinal plants in the treatment of cancer, and also outlines methodologies that can also be used to achieve better outcomes for cancer treatment. This review outlines African medicinal plants, isolated compounds and technologies that can be used to advance cancer research. Chemical structures of isolated compounds have an important role in anti-cancer treatments; new technologies and methods may assist to identify more properties of African medicinal plants and the treatment of cancer. In conclusion, African medicinal plants have shown their potential as enormous resources for novel cytotoxicity compounds. Finally it has been noted that the cytotoxicity depends on the chemical structural arrangements of African medicinal plants compounds.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Plantas Medicinais/química , África , Humanos , Fitoterapia
12.
Exp Mol Pathol ; 98(3): 585-92, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25779024

RESUMO

Ceramide synthases (CerSs) also known as Longevity Assurance (LASS) genes belong to a family of six related genes. CerS gene products have been shown to produce ceramide, hence their name CerSs. Ceramide is a bio-effector molecule, belonging to the family of sphingolipids (SLs), which are important components of cell membranes, and has been implicated in cancer and apoptosis. Cancer still remains the second leading cause of death, both globally and in South Africa. The proper regulation of the balance between cell growth and cell death is essential for cellular homeostasis. Failure to properly regulate this balance may lead to pathologic conditions such as cancer development. CerSs have been implicated in cancer biology, especially in apoptosis, through the action of ceramide. Although knowledge of the role that CerSs play in cancer biology is advancing, the precise roles of distinct CerSs in different cancers are not yet fully understood, especially the roles of CerS4 and CerS5 in endometrial and colon cancers. The aim of this study was to investigate the link of CerS4 and CerS5 in apoptosis and, thus in cancers of the endometrium and colon, which are amongst the most prevalent cancers globally. Apoptosis was induced using anastrozole in endometrial cells and 5-FU in colon cells. Fluorescence activated cell sorting was used to analyse and quantify apoptosis and total RNA was extracted from both treated and untreated cells. Quantitative relative expression of CerS4 and CerS5 mRNA was then determined in all cells (treated and untreated), normalised to ß-actin. Bio-informatics was used to compare CerS4 and CerS5 sequences. The endometrial cancer cells were more prone to apoptosis compared to their non-cancerous counterparts, while the colon cancer cells were more responsive to apoptosis induction after 48h, especially the HT-29 cells. Using quantitative real-time PCR, both CerS4 and CerS5 were shown to be up-regulated in endometrial and colon cancer cells. Apoptosis induction resulted in down-regulation of CerS4 and CerS5 in endometrial and colon cancers. These findings implicate these genes in cancer and apoptosis. Whether these genes play pro- or anti-apoptotic roles in cancers of the endometrium and colon is not conclusive at this stage. It may also be possible that these genes could exert opposing roles in the same or different tissues. Targeting this family of genes and understanding their precise individual roles in different types of cancer, are a promising therapeutic tool to new anti-cancer drug discovery or improving existing treatments.


Assuntos
Apoptose , Neoplasias do Colo/metabolismo , Neoplasias do Endométrio/metabolismo , Esfingosina N-Aciltransferase/metabolismo , Sequência de Aminoácidos , Células CACO-2 , Regulação para Baixo , Feminino , Células HT29 , Humanos , Dados de Sequência Molecular , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Esfingosina N-Aciltransferase/genética
13.
Exp Mol Pathol ; 2015 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-25794975

RESUMO

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.yexmp.2015.03.023. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

14.
Exp Mol Pathol ; 98(3): 574-84, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25794976

RESUMO

Pyruvate dehydrogenase kinase 4 (PDK4), a mammalian mitochondrial serine kinase has emerged as an interesting candidate for diabetes therapy. Due to the high prevalence of this disease especially type 2 diabetes (T2D) and the health complications associated with it, there is extensive effort to find the appropriate treatment. Understanding the regulation of PDK4 activity would therefore contribute significantly to the development of therapeutic agents. This research outlines the utilization of bioinformatics tools such as Interweaver, ClustalW and Protein Structure Visualizer, in order to predict proteins that potentially interact with PDK4 and possibly regulate its activity. Interweaver database identified 96 proteins that have possible interaction sites for PDK4. Protein p100/p49, containing a death domain that is known to have a role in suppressing apoptosis, was identified as a potential partner for PDK4. The alignment between p100/p49 primary sequence and that of PDK4 using ClustalW demonstrated sequence similarity between the two proteins. Swiss PDB Viewer then located the positions of the amino acids that are in the hypothetical protein binding motif of p100/p49 within the 3D structure of hPDK4. These amino acids were found to be located in the region of PDK4 which is known to bind protein substrates of PDK4 and may be accessible to other proteins as well. These findings were very interesting as PDK4 has not previously been associated with apoptosis and this could be the link between apoptosis and insulin resistance. Cell biology studies were then performed to verify the relationship between PDK4 and apoptosis. In this regard, HeLa and HepG2 cells were treated with apoptosis-inducing agents such as TNFα, C2-ceramide, and linoleic acid. These cells were then monitored for apoptosis and PDK4 mRNA expression using a DNA laddering assay as well as Real Time PCR. The results showed that these factors induced apoptosis in a concentration dependent manner and suppressed PDK4 mRNA levels. These findings suggested a relationship between PDK4 and apoptosis.


Assuntos
Apoptose , Proteínas Serina-Treonina Quinases/química , Motivos de Aminoácidos , Sequência de Aminoácidos , Sítios de Ligação , Células HeLa , Células Hep G2 , Humanos , Resistência à Insulina , Dados de Sequência Molecular , Subunidade p52 de NF-kappa B/química , Subunidade p52 de NF-kappa B/metabolismo , Ligação Proteica , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
15.
Exp Mol Pathol ; 99(1): 74-80, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25910411

RESUMO

South Africa has one of the highest HIV infection rates in the world. One of the complications of HIV infection is the development of HIV-associated nephropathy (HIVAN), which is characterized by deregulation in tubular epithelial apoptosis. The pathways that HIV-1 promotes in the pathogenesis of HIVAN remain less understood. There are many genes that have not been characterized in the pathogenesis of HIVAN. On the other hand, RBBP6 has been shown to play a role in both promoting and inhibiting apoptosis in human cancers. This study was aimed at determining an association between RBBP6 isoform 3 expression and the levels of apoptosis in HIVAN cases. HIVAN biopsy tissues from Johannesburg patients in South Africa were used in this study. These tissues were stained for RBBP6 expression and apoptosis levels using immunohistochemistry staining and TUNEL method respectively. Image analysis was used for quantitative analysis and GraphPad Version 4 was used for statistical analysis. High expression levels of RBBP6 were found in HIVAN cases (n=30) relative to the normal tissues (n=10). High apoptosis levels were also obtained in the HIVAN tissues. This direct association between RBBP6 expression and apoptosis levels suggests that RBBP6 may play a role in HIVAN pathogenesis. RBBP6 may then be targeted for both diagnostic and therapeutic strategies in HIVAN.


Assuntos
Nefropatia Associada a AIDS/genética , Apoptose , Proteínas de Transporte/genética , Proteínas de Ligação a DNA/genética , Variação Genética , Proteínas de Transporte/metabolismo , Fragmentação do DNA , Proteínas de Ligação a DNA/metabolismo , Células HEK293 , Humanos , Processamento de Imagem Assistida por Computador , Hibridização In Situ , Marcação In Situ das Extremidades Cortadas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , África do Sul , Técnicas de Cultura de Tecidos , Ubiquitina-Proteína Ligases
16.
Int J Mol Sci ; 16(11): 27171-90, 2015 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-26580598

RESUMO

Apoptosis is required for normal heart development in the embryo, but has also been shown to be an important factor in the occurrence of heart disease. Alternative splicing of apoptotic genes is currently emerging as a diagnostic and therapeutic target for heart disease. This review addresses the involvement of abnormalities in alternative splicing of apoptotic genes in cardiac disorders including cardiomyopathy, myocardial ischemia and heart failure. Many pro-apoptotic members of the Bcl-2 family have alternatively spliced isoforms that lack important active domains. These isoforms can play a negative regulatory role by binding to and inhibiting the pro-apoptotic forms. Alternative splicing is observed to be increased in various cardiovascular diseases with the level of alternate transcripts increasing elevated in diseased hearts compared to healthy subjects. In many cases these isoforms appear to be the underlying cause of the disease, while in others they may be induced in response to cardiovascular pathologies. Regardless of this, the detection of alternate splicing events in the heart can serve as useful diagnostic or prognostic tools, while those splicing events that seem to play a causative role in cardiovascular disease make attractive future drug targets.


Assuntos
Processamento Alternativo , Apoptose/genética , Doenças Cardiovasculares/genética , Regulação da Expressão Gênica , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Cardiomiopatias/genética , Cardiomiopatias/metabolismo , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/terapia , Humanos , Transdução de Sinais
17.
Front Endocrinol (Lausanne) ; 15: 1422599, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38832352

RESUMO

RNA biology has revolutionized cancer understanding and treatment, especially in endocrine-related malignancies. This editorial highlights RNA's crucial role in cancer progression, emphasizing its influence on tumor heterogeneity and behavior. Processes like alternative splicing and noncoding RNA regulation shape cancer biology, with microRNAs, long noncoding RNAs, and circular RNAs orchestrating gene expression dynamics. Aberrant RNA signatures hold promise as diagnostic and prognostic biomarkers in endocrine-related cancers. Recent findings, such as aberrant PI3Kδ splice isoforms and epithelial-mesenchymal transition-related lncRNA signatures, unveil potential therapeutic targets for personalized treatments. Insights into m6A-associated lncRNA prognostic models and the function of lncRNA LINC00659 in gastric cancer represents ongoing research in this field. As understanding of RNA's role in cancer expands, personalized therapies offer transformative potential in managing endocrine-related malignancies. This signifies a significant stride towards precision oncology, fostering innovation for more effective cancer care.


Assuntos
Neoplasias , Humanos , Neoplasias/genética , Neoplasias/terapia , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Biomarcadores Tumorais/genética , MicroRNAs/genética , Medicina de Precisão/métodos , RNA/genética , RNA Circular/genética , Animais
18.
Cancers (Basel) ; 16(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38473432

RESUMO

Despite significant progress in the prevention, screening, diagnosis, prognosis, and therapy of breast cancer (BC), it remains a highly prevalent and life-threatening disease affecting millions worldwide. Molecular subtyping of BC is crucial for predictive and prognostic purposes due to the diverse clinical behaviors observed across various types. The molecular heterogeneity of BC poses uncertainties in its impact on diagnosis, prognosis, and treatment. Numerous studies have highlighted genetic and environmental differences between patients from different geographic regions, emphasizing the need for localized research. International studies have revealed that patients with African heritage are often diagnosed at a more advanced stage and exhibit poorer responses to treatment and lower survival rates. Despite these global findings, there is a dearth of in-depth studies focusing on communities in the African region. Early diagnosis and timely treatment are paramount to improving survival rates. In this context, radiogenomics emerges as a promising field within precision medicine. By associating genetic patterns with image attributes or features, radiogenomics has the potential to significantly improve early detection, prognosis, and diagnosis. It can provide valuable insights into potential treatment options and predict the likelihood of survival, progression, and relapse. Radiogenomics allows for visual features and genetic marker linkage that promises to eliminate the need for biopsy and sequencing. The application of radiogenomics not only contributes to advancing precision oncology and individualized patient treatment but also streamlines clinical workflows. This review aims to delve into the theoretical underpinnings of radiogenomics and explore its practical applications in the diagnosis, management, and treatment of BC and to put radiogenomics on a path towards fully integrated diagnostics.

19.
Noncoding RNA Res ; 9(3): 887-900, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38616862

RESUMO

In the intricate field of cancer biology, researchers are increasingly intrigued by the emerging role of exosomal long non-coding RNAs (lncRNAs) due to their multifaceted interactions, complex modulation mechanisms, and potential therapeutic applications. These exosomal lncRNAs, carried within extracellular vesicles, play a vital partin tumorigenesis and disease progression by facilitating communication networks between tumor cells and their local microenvironment, making them an ideal candidates for use in a liquid biopsy approach. However, exosomal lncRNAs remain an understudied area, especially in cancer biology. Therefore this review aims to comprehensively explore the dynamic interplay between exosomal lncRNAs and various cellular components, including interactions with tumor-stroma, immune modulation, and drug resistance mechanisms. Understanding the regulatory functions of exosomal lncRNAs in these processes can potentially unveil novel diagnostic markers and therapeutic targets for cancer. Additionally, the emergence of RNA-based therapeutics presents exciting opportunities for targeting exosomal lncRNAs, offering innovative strategies to combat cancer progression and improve treatment outcomes. Thus, this review provides insights into the current understanding of exosomal lncRNAs in cancer biology, highlighting their crucial roles, regulatory mechanisms, and the evolving landscape of therapeutic interventions. Furthermore, we have also discussed the advantage of exosomes as therapeutic carriers of lncRNAs for the development of personalized targeted therapy for cancer patients.

20.
Oncol Ther ; 12(1): 1-11, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37910378

RESUMO

The formidable impact of breast cancer extends globally, with South Africa facing pronounced challenges, including significant disparities in breast cancer screening, treatment and survival along ethnic and socioeconomic lines. Over the last two decades, breast cancer incidence has increased and now accounts for a substantial portion of cancers in women. Ethnic disparities in terms of screening, incidence and survival exacerbate the issue, leading to delayed diagnosis among Black patients and highlighting healthcare inequities. These concerning trends underscore the urgency of enhancing breast cancer screening while mitigating treatment delays, although obstacles within the healthcare system impede progress. The intersection of breast cancer and human immunodeficiency virus (HIV) further complicates matters and particularly affects the Black population. Tackling the aforementioned disparities in breast cancer in South Africa mandates a multifaceted strategy. Robust screening efforts, particularly those targeting marginalised communities, are crucial for early detection. Concurrently, expedited treatment initiation is imperative. Addressing HIV-related complexities requires tailored interventions to ensure effective care. These multifaceted disparities require pan African research and cooperation as well as tailored interventions to enhance breast cancer care within the African region.

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