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1.
Med Oncol ; 41(6): 148, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733486

RESUMO

Numerous herbal products have been the subject of research regarding their potential role in cancer prevention or adjuvant therapy. Pistacia atlantica and its main phytochemicals have garnered significant attention for their potential anti-cancer effects. The study aimed to assess the growth inhibitory effects of P. atlantica essential oil (PAEO) on MKN-45 and AGS cells. This study quantified the volatile compounds in PAEO using Gas Chromatography-Mass Spectrometry (GC-MS). Subsequently, MKN-45 and AGS cells were treated with varying concentrations of PAEO (5%, 2.5%, 1.25%, 0.625%, 0.3125%, 0.156%, 0.0781%, 0.0391%, 0.0195%) for 24 h. Cell viability was evaluated through the MTT assay. The impact of PAEO on gene expression was investigated by quantifying the mRNA levels of Bax and Bcl2 in the various experimental groups using quantitative Real-Time PCR (qRT-PCR) analysis. Additionally, flow cytometry was utilized to evaluate apoptosis in the treated cells. The analysis of PAEO revealed that α-pinene was the predominant monoterpene, constituting 87.9% of the oil composition. The cytotoxic effects of PAEO were evaluated, and it was found that the oil significantly reduced the viability of MKN-45 and AGS cells. The IC50 for MKN-45 cells was determined to be 1.94 × 10-3% after 24 h of treatment, while for AGS cells the IC50 was 2.8 × 10-3% after 24 h. Additionally, the research revealed that PAEO triggered a notable rise in apoptotic cells in both AGS and MKN-45 cell lines. Moreover, at the molecular level, the findings indicated an increase in Bax expression and a decrease in Bcl2 mRNA expression, providing further evidence of the induction of apoptosis in both MKN-45 and AGS cell lines following PAEO treatment. The findings of this study offer evidence supporting the cytotoxic effects of PAEO on gastric cancer cell lines by promoting apoptosis. The findings suggest that PAEO may offer potential as a therapeutic candidate in managing and treating gastric cancer.


Assuntos
Apoptose , Sobrevivência Celular , Óleos Voláteis , Pistacia , Neoplasias Gástricas , Humanos , Óleos Voláteis/farmacologia , Pistacia/química , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/genética , Cromatografia Gasosa-Espectrometria de Massas
2.
Rev Med Virol ; 34(2): e2530, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38517354

RESUMO

A significant portion of human cancers are caused by oncoviruses (12%-25%). Oncoviruses employ various strategies to promote their replication and induce tumourigenesis in host cells, one of which involves modifying the gene expression patterns of the host cells, leading to the rewiring of genes and resulting in significant changes in cellular processes and signalling pathways. In recent studies, a specific mode of gene regulation known as circular RNA (circRNA)-mediated competing endogenous RNA (ceRNA) networks has emerged as a key player in this context. CircRNAs, a class of non-coding RNA molecules, can interact with other RNA molecules, such as mRNAs and microRNAs (miRNAs), through a process known as ceRNA crosstalk. This interaction occurs when circRNAs, acting as sponges, sequester miRNAs, thereby preventing them from binding to their target mRNAs and modulating their expression. By rewiring the host cell genome, oncoviruses have the ability to manipulate the expression and activity of circRNAs, thereby influencing the ceRNA networks that can profoundly impact cellular processes such as cell proliferation, differentiation, apoptosis, and immune responses. This review focuses on a comprehensive evaluation of the latest findings on the involvement of virus-induced reprogramming of host circRNA-mediated ceRNA networks in the development and pathophysiology of human viral cancers, including cervical cancer, gastric cancer, nasopharyngeal carcinoma, Kaposi's sarcoma, hepatocellular carcinoma, and diffuse large B cell lymphoma. Understanding these mechanisms can improve our knowledge of how oncoviruses contribute to human tumourigenesis and identify potential targets for developing optimised therapies and diagnostic tools for viral cancers.


Assuntos
Neoplasias Hepáticas , MicroRNAs , Humanos , MicroRNAs/genética , RNA Circular/genética , RNA Mensageiro/metabolismo , RNA Endógeno Competitivo , Retroviridae/genética , Retroviridae/metabolismo , Perfilação da Expressão Gênica/métodos , Carcinogênese/genética
3.
Arch Biochem Biophys ; 753: 109930, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38369227

RESUMO

Metastasis is a significant clinical challenge responsible for cancer mortality and non-response to treatment. However, the molecular mechanisms driving metastasis remain unclear, limiting the development of efficient diagnostic and therapeutic approaches. Recent breakthroughs in cancer biology have discovered a group of small non-coding RNAs called tRNA-derived fragments (tRFs), which play a critical role in the metastatic behavior of various tumors. tRFs are produced from cleavage modifications of tRNAs and have different functional classes based on the pattern of these modifications. They perform post-transcriptional regulation through microRNA-like functions, displacing RNA-binding proteins, and play a role in translational regulation by inducing ribosome synthesis, translation initiation, and epigenetic regulation. Tumor cells manipulate tRFs to develop and survive the tumor mass, primarily by inducing metastasis. Multiple studies have demonstrated the potential of tRFs as therapeutic, diagnostic, and prognostic targets for tumor metastasis. This review discusses the production and function of tRFs in cells, their aberrant molecular contributions to the metastatic environment, and their potential as promising targets for anti-metastasis treatment strategies.


Assuntos
MicroRNAs , Neoplasias , Humanos , Epigênese Genética , RNA de Transferência/genética , RNA de Transferência/metabolismo , Neoplasias/diagnóstico , Neoplasias/terapia , Neoplasias/genética , Regulação da Expressão Gênica
4.
Biochem Biophys Rep ; 37: 101644, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38298209

RESUMO

Exosomes are a type of extracellular vesicle that contains bioactive molecules that can be secreted by most cells. Nevertheless, the content of these cells differs depending on the cell from which they originate. The exosome plays a crucial role in modulating intercellular communication by conveying molecular messages to neighboring or distant cells. Cancer-derived exosomes can transfer several types of molecules into the tumor microenvironment, including high levels of microRNA (miRNA). These miRNAs significantly affect cell proliferation, angiogenesis, apoptosis resistance, metastasis, and immune evasion. Increasing evidence indicates that exosomal miRNAs (exomiRs) are crucial to regulating cancer resistance to apoptosis. In cancer cells, exomiRs orchestrate communication channels between them and their surrounding microenvironment, modulating gene expression and controlling apoptosis signaling pathways. This review presents an outline of present-day knowledge of the mechanisms that affect target cells and drive cancer resistance to apoptosis. Also, our study looks at the regulatory role of exomiRs in mediating intercellular communication between tumor cells and surrounding microenvironmental cells, specifically stromal and immune cells, to evade therapy-induced apoptosis.

5.
Adv Med Sci ; 68(2): 450-463, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37926001

RESUMO

Recent events have raised concerns about the outbreak of a pandemic by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An infection caused by a virus can provoke an inflammatory reaction, which can result in severe lung damage, failure of several organs, and death. The unique genetic makeup of each individual may be a component in the development of each of these responses. In this context, genetic variants of the genes linked to the invasion of the virus into the host's body can be analyzed. Various elements have a function in viral entry. ACE2 is used by SARS-CoV-2 as a receptor to enter the cell. TMPRSS2 is then responsible for cutting the virus into its components. In addition, lung damage occurs when there is an imbalance between ACE1 and ACE2. Another component that plays a significant role in virus penetration is called IFITM3, which is created as a reaction to interferon. This protein prevents viruses in the Coronaviridae family from entering cells. This study aimed to analyze DNA polymorphisms in the ACE2, ACE1, TMPRSS2, and IFITM3 genes. Findings showed certain polymorphisms appear to be associated with the severity of the disease, including respiratory, coronary, and neurological disorders. The results also indicated that certain polymorphisms were protective against this virus. Varying populations have a different frequency of high-risk polymorphisms, so different treatment and preventative techniques must be implemented. Additional population studies should be conducted in this region to reduce the incidence of COVID-19-related morbidity and mortality.


Assuntos
COVID-19 , Humanos , COVID-19/genética , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Polimorfismo Genético , Incidência , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas de Ligação a RNA/genética , Serina Endopeptidases/genética
6.
Exp Cell Res ; 423(1): 113442, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36521777

RESUMO

Cancer is responsible for about one in six deaths in the world. Conventional cancer treatments like chemotherapy, radiotherapy, and surgery are associated with drug poisoning and poor prognosis. Thanks to advances in RNA delivery and target selection, new cancer medicines are now conceivable to improve the quality of life and extend the lives of cancer patients. Antisense oligonucleotides (ASOs) and siRNAs are the most important tools in RNA therapies. Locked Nucleic Acids (LNAs) are one of the newest RNA analogs, exhibiting more affinity to binding, sequence specificity, thermal stability, and nuclease resistance due to their unique properties. Assays using LNA are also used in molecular diagnostic methods and provide accurate and rapid mutation detection that improves specificity and sensitivity. This study aims to review the special properties of LNA oligonucleotides that make them safe and effective antisense drugs for cancer treatment by controlling gene expression. Following that, we go over all of the molecular detection methods and cancer treatment antisense tactics that are possible with LNA technology.


Assuntos
Neoplasias , Qualidade de Vida , Humanos , Oligonucleotídeos/genética , Oligonucleotídeos/uso terapêutico , Oligonucleotídeos/química , Oligonucleotídeos Antissenso/genética , Oligonucleotídeos Antissenso/uso terapêutico , Oligonucleotídeos Antissenso/química , RNA , Conformação de Ácido Nucleico , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/terapia
7.
J Cell Commun Signal ; 17(3): 639-655, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36149574

RESUMO

Thyroid cancer (TC) is the most common endocrine cancer, accounting for 1.7% of all cancer cases. It has been reported that the existing approach to diagnosing TC is problematic. Therefore, it is essential to develop molecular biomarkers to improve the accuracy of the diagnosis. This study aimed to screen hub lncRNAs in the ceRNA network (ceRNET) connected to TC formation and progression based on the overall survival rate. In this study, first, RNA-seq data from the GDC database were collected. A package called edgeR in R programming language was then used to obtain differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) in TC patients' samples compared to normal samples. Second, DEmRNAs were analyzed for their functional enrichment. Third, to identify RNAs associated with overall survival, the overall survival of these RNAs was analyzed using the Kaplan-Meier plotter database to create a survival associated with the ceRNA network (survival-related ceRNET). Next, the GeneMANIA plugin was used to construct a PPI network to better understand survival-related DEmRNA interactions. The survival ceRNET was then visualized with the Cytoscape software, and hub genes, including hub lncRNAs and hub mRNAs, were identified using the CytoHubba plugin. We found 45 DElncRNAs, 28 DEmiRNAs, and 723 DEmRNAs among thyroid tumor tissue and non-tumor tissue samples. According to KEGG, GO and DO analyses, 723 DEmRNAs were mainly enriched in cancer-related pathways. Importantly, the results found that ten DElncRNAs, four DEmiRNAs, and 68 DEmRNAs are associated with overall survival. In this account, the PPI network was constructed for 68 survival-related DEmRNAs, and ADAMTS9, DTX4, and CLDN10 were identified as hub genes. The ceRNET was created by combining six lncRNAs, 109 miRNAs, and 22 mRNAs related to survival using Cytoscape. in this network, ten hub RNAs were identified by the CytoHubba plugin, including mRNAs (CTXND1, XKRX, IGFBP2, ENTPD1, GALNT7, ADAMTS9) and lncRNAs (AC090673.1, AL162511.1, LINC02454, AL365259.1). This study suggests that three lncRNAs, including AL162511.1, AC090673.1, and AL365259.1, could be reliable diagnostic biomarkers for TC. The findings of this study provide a basis for future studies on the therapeutic potential of these lncRNAs.

8.
Biomed Pharmacother ; 142: 111999, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34385106

RESUMO

Residing on chromosome 20q13.13, Zinc Finger NFX1-Type Containing 1 (ZNFX1) antisense RNA 1 (ZFAS1) is a transcript which has been primarily recognized as a modulator of differentiation of alveolar and epithelial cell in the mammary gland. This long non-coding RNA (lncRNA) partakes in the molecular cascades leading to several non-neoplastic conditions such as osteoarthritis, epilepsy, rheumatoid arthritis, atherosclerosis, pulmonary fibrosis, myocardial infarction, and cardiac dysfunction. More importantly, ZFAS1 is considered as an oncogene in almost all types of cancers. Using expression amounts of ZFAS1, it is possible to forecast the clinical outcome of patients with different neoplasms such as colorectal cancer, gastric cancer, cholangiocarcinoma, hepatoblastoma, and other types of cancer. We describe the role of ZFAS1 in the development of neoplastic and non-neoplastic disorders.


Assuntos
Carcinogênese/genética , Neoplasias/genética , RNA Longo não Codificante/genética , Animais , Humanos , Neoplasias/patologia
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