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1.
Epigenetics ; 18(1): 2175522, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38016026

RESUMO

Ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) is highly expressed in smokers, but little is known about the molecular mechanism of UCHL1 in airway epithelium and its possible role in affecting extracellular matrix (ECM) remodelling in the underlying submucosa. Since cigarette smoking is a major cause of lung diseases, we studied its effect on UCHL1 expression and DNA methylation patterns in human bronchial epithelial cells, obtained after laser capture micro-dissection (LCM) or isolated from residual tracheal/main stem bronchial tissue. Targeted regulation of UCHL1 expression via CRISPR/dCas9 based-epigenetic editing was used to explore the function of UCHL1 in lung epithelium. Our results show that cigarette smoke extract (CSE) stimulated the expression of UCHL1 in vitro. The methylation status of the UCHL1 gene was negatively associated with UCHL1 transcription in LCM-obtained airway epithelium at specific sites. Treatment with a UCHL1 inhibitor showed that the TGF-ß1-induced upregulation of the ECM gene COL1A1 can be prevented by the inhibition of UCHL1 activity in cell lines. Furthermore, upon downregulation of UCHL1 by epigenetic editing using CRISPR/dCas-EZH2, mRNA expression of COL1A1 and fibronectin was reduced. In conclusion, we confirmed higher UCHL1 expression in current smokers compared to non- and ex-smokers, and induced downregulation of UCHL1 by epigenetic editing. The subsequent repression of genes encoding ECM proteins suggest a role for UCHL1 as a therapeutic target in fibrosis-related disease.


Assuntos
Metilação de DNA , Epigênese Genética , Humanos , Brônquios , Colágeno/metabolismo , Células Epiteliais , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo
2.
J Proteome Res ; 22(10): 3103-3122, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37725793

RESUMO

For years, the paths of sequencing technologies and mass spectrometry have occurred in isolation, with each developing its own unique culture and expertise. These two technologies are crucial for inspecting complementary aspects of the molecular phenotype across the central dogma. Integrative multiomics strives to bridge the analysis gap among different fields to complete more comprehensive mechanisms of life events and diseases. Proteogenomics is one integrated multiomics field. Here in this review, we mainly summarize and discuss three aspects: workflow of proteogenomics, proteogenomics applications in cancer research, and the SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis of proteogenomics in cancer research. In conclusion, proteogenomics has a promising future as it clarifies the functional consequences of many unannotated genomic abnormalities or noncanonical variants and identifies driver genes and novel therapeutic targets across cancers, which would substantially accelerate the development of precision oncology.

4.
Clin Epigenetics ; 15(1): 85, 2023 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-37179342

RESUMO

Epigenetic memory is essential for life that governs the predefined functional features of cells. Recent evidence has indicated that the epigenetic modification provides a potential link to gene expression changes that may be involved in the development of various chronic diseases, and targeting the epigenome becomes a plausible method for treating diseases. Traditional herbal medicine has gradually entered the vision of researchers due to its low toxicity and its effectiveness in treating diseases. As a matter of fact, researchers found that the possessed epigenetic modification capacity of herbal medicine had the ability to combat the progression of the disease, such as various types of cancer, diabetes, inflammation, amnesia, liver fibrosis, asthma, and hypertension-induced renal injury. Studies on the epigenetic effects of herbal medicine will provide valuable insights into the molecular mechanisms of human diseases, which may lead to new therapeutic approaches and diagnoses. Thus, this review summarized the impact of herbal medicine and its bioactive components on disease epigenome as examples of how utilization of epigenetic plasticity could be useful as the basis for the future development of targeted therapies in chronic diseases.


Assuntos
Metilação de DNA , Rim , Humanos , Rim/metabolismo , Epigênese Genética , Doença Crônica , Extratos Vegetais
5.
Int J Mol Sci ; 24(7)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37047039

RESUMO

The human eukaryotic translation initiation factor 5A (EIF5A) family consists of three members, namely EIF5A1, EIF5A2, and EIF5AL1. Recent studies have shown that the expression of EIF5As is related to many human diseases, such as diabetes, viral infection, central nervous system injury, and cancer. Among them, EIF5A1 plays different functions in various cancers, possibly as a tumor-suppressor or oncogene, while EIF5A2 promotes the occurrence and development of cancer. Yet, the biological function of EIF5AL1 is not being studied so far. Interestingly, although there are only three amino acid (at residues 36, 45, and 109) differences between EIF5A1 and EIF5AL1, we demonstrate that only EIF5A1 can be hypusinated while EIF5AL1 cannot, and EIF5AL1 has a tumor-suppressor-like function by inhibiting cell proliferation and migration. We also show that EIF5AL1 protein turnover is mediated through the proteasomal pathway, and EIF5AL1 protein turnover is much faster than that of EIF5A1, which may explain their differential protein expression level in cells. By engineering single and double mutations on these three amino acids, we pinpoint which of these amino acids are critical for hypusination and protein stability. The data of this work should fill in the gaps in EIF5As research and pave the way for future studies on EIF5AL1.


Assuntos
Lisina , Neoplasias , Humanos , Aminoácidos , Fatores de Iniciação em Eucariotos/genética , Fatores de Iniciação em Eucariotos/metabolismo , Lisina/metabolismo , Neoplasias/metabolismo , Fatores de Iniciação de Peptídeos/genética , Fatores de Iniciação de Peptídeos/metabolismo , Estabilidade Proteica , Fator de Iniciação de Tradução Eucariótico 5A
6.
Cancers (Basel) ; 15(5)2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36900191

RESUMO

Studying the relatively underexplored atypical MAP Kinase MAPK15 on cancer progression/patient outcomes and its potential transcriptional regulation of downstream genes would be highly valuable for the diagnosis, prognosis, and potential oncotherapy of malignant tumors such as lung adenocarcinoma (LUAD). Here, the expression of MAPK15 in LUAD was detected by immunohistochemistry and its correlation with clinical parameters such as lymph node metastasis and clinical stage was analyzed. The correlation between the prostaglandin E2 receptor EP3 subtype (EP3) and MAPK15 expression in LUAD tissues was examined, and the transcriptional regulation of EP3 and cell migration by MAPK15 in LUAD cell lines were studied using the luciferase reporter assay, immunoblot analysis, qRT-PCR, and transwell assay. We found that MAPK15 is highly expressed in LUAD with lymph node metastasis. In addition, EP3 is positively correlated with the expression of MAPK15 in LUAD tissues, and we confirmed that MAPK15 transcriptionally regulates the expression of EP3. Upon the knockdown of MAPK15, the expression of EP3 was down-regulated and the cell migration ability was decreased in vitro; similarly, the mesenteric metastasis ability of the MAPK15 knockdown cells was inhibited in in vivo animal experiments. Mechanistically, we demonstrate for the first time that MAPK15 interacts with NF-κB p50 and enters the nucleus, and NF-κB p50 binds to the EP3 promoter and transcriptionally regulates the expression of EP3. Taken together, we show that a novel atypical MAPK and NF-κB subunit interaction promotes LUAD cell migration through transcriptional regulation of EP3, and higher MAPK15 level is associated with lymph node metastasis in patients with LUAD.

7.
Molecules ; 28(4)2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36838754

RESUMO

In this review, we discuss the recent knowledge regarding the epigenetic effects of coffee extract and the three essential active ingredients in coffee (caffeine, chlorogenic acid, and caffeic acid). As a popular beverage, coffee has many active ingredients which have a variety of biological functions such as insulin sensitization, improvement of sugar metabolism, antidiabetic properties, and liver protection. However, recent researches have shown that coffee is not only beneficial for human, but also bad, which may be due to its complex components. Studies suggest that coffee extract and its components can potentially impact gene expression via alteration of DNA methylation, histone modifications, and ncRNA expression; thus, exert long lasting impacts on the epigenome. More importantly, coffee consumption during pregnancy has been linked to multiple negative effects on offspring due to epigenetic modifications; on the other hand, it has also been linked to improvements in many diseases, including cancer. Therefore, understanding more about the epigenetic effects associated with coffee components is crucial to finding ways for improving human health.


Assuntos
Ácido Clorogênico , Café , Epigênese Genética , Humanos , Cafeína/farmacologia , Ácido Clorogênico/farmacologia , Hipoglicemiantes/farmacologia , Fígado , Café/química
8.
Int J Mol Sci ; 25(1)2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38203280

RESUMO

Mitogen-activated protein kinase 15 (MAPK15) has been reported to be associated with several cancers. This study aimed to explore for the first time on the relationship between MAPK15 expression and cancer progression/drug responsiveness in ovarian carcinoma. To this end, MAPK15 expression level was examined by immunohistochemistry (IHC) staining of an ovarian tissue array (10 normal and 70 malignant samples). Drug sensitivity of ovarian cancer cell lines (including OVCAR3 and SKOV3) was measured by MTS assay. The modulation of MAPK15 expression in OVCAR3 and SKOV3 was verified by immunoblot and real-time PCR analyses. The prognostic value of MAPK15 in ovarian cancer patients was assessed using the Kaplan-Meier Plotter database and Gene Expression Omnibus (GEO) datasets. The IHC results showed that MAPK15 expression was negatively associated with tumor grade, TNM stage, tumor size, and regional lymph node metastasis of ovarian carcinoma. Importantly, overexpressing MAPK15 increased cisplatin toxicity in ovarian carcinoma cells and online database analysis indicated that patients with high MAPK15 expression had favorable prognosis with/without chemotherapy. Taken together, our results indicate that a decreased MAPK15 expression is associated with advanced-stage ovarian cancer and unfavorable survival outcomes. MAPK15 may be a new biomarker for ovarian cancer, and the encouraging therapeutic strategy would be found by combining the regulation of MAPK15 expression.


Assuntos
Carcinoma , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Apoptose , Linhagem Celular Tumoral , Carcinoma Epitelial do Ovário , Biomarcadores , MAP Quinases Reguladas por Sinal Extracelular
9.
Front Mol Biosci ; 9: 991308, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330220

RESUMO

Human transmembrane protein metal cation symporter ZIP8 (SLC39A8) is a member of the solute carrier gene family responsible for intracellular transportation of essential micronutrients, including manganese, selenium, and zinc. Previously, we established a ZIP8-knockout (KO) human cell model using the CRISPR/Cas9 system and explored how the expression of ZIP8 could possibly contribute to a wide range of human diseases. To further assess the biophysiological role of ZIP8, in the current study, we employed isobaric tags for relative and absolute quantitation (iTRAQ) and detected the changes of the proteome in ZIP8-KO cells (proteomic data are available via ProteomeXchange with identifier PXD036680). A total of 286 differentially expressed proteins (206 downregulated and 80 upregulated proteins) were detected in the ZIP8-KO cell model, and subsequent bioinformatics analyses (GO, KEGG, KOG, and PPI) were performed on these proteins. Interestingly, four "uncharacterized" proteins (proteins with unknown biological function) were identified in the differentially expressed proteins: C1orf198, C9orf85, C17orf75, and CXorf38-all of which were under-expressed in the ZIP8-KO cells. Notably, C9orf85 and CXorf38 were amongst the top-10 most downregulated proteins, and their expressions could be selectively induced by essential micronutrients. Furthermore, clinical-based bioinformatic analysis indicated that positive correlations between the gene expressions of ZIP8 and C9orf85 or CXorf38 were observed in multiple cancer types. Overall, this study reveals the proteomic landscape of cells with impaired ZIP8 and uncovers the potential relationships between essential micronutrients and uncharacterized proteins C9orf85 and CXorf38. The differentially expressed proteins identified in ZIP8-KO cells could be the potential targets for diagnosing and/or treating human ZIP8-associated diseases, including but not limited to malnutrition, viral infection, and cancers.

10.
Environ Sci Pollut Res Int ; 29(60): 89874-89888, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36367641

RESUMO

Cadmium (Cd) is a toxic non-essential heavy metal. Chronic low Cd exposure (CLCE) has been associated with distinct pathologies in many organ systems, including liver and kidney damage, osteoporosis, carcinogenicity, or reproductive toxicity. Currently, about 10% of the global population is at risk of CLCE. It is urgent to find robust and effective biomarkers for early diagnosis of Cd exposure and treatment. Metabolomics is a high-throughput method based on mass spectrometry to study the dynamic changes in a series of endogenous small molecular metabolites (typically < 1000 Da) of tissues, cells, or biofluids. It can reflect the rich and complex biochemical changes in the body after exposure to heavy metals, which may be useful in screening biomarkers to monitor exposure to environmental pollutants and/or predict disease risk. Therefore, this review focuses on the changes in metabolic profiles of humans and rodents under long-term Cd exposure from the perspective of metabolomics. Furthermore, the relationship between the disturbance of metabolic pathways and the toxic mechanism of Cd is discussed. All these information will facilitate the development of reliable metabolic biomarkers for early detection and diagnosis of Cd-related diseases.


Assuntos
Cádmio , Metabolômica , Humanos , Cádmio/toxicidade
11.
iScience ; 25(12): 105459, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36425765

RESUMO

The efficacy of cisplatin in treating advanced non-small cell lung cancer is limited mainly because of insensitivity and/or acquired resistance. MAPK15, previously shown by us to enhance the sensitivity of the anti-cancer drug arsenic trioxide, could also enhance the sensitivity of other anti-cancer drugs. Here, we explore the potential role of MAPK15 in chemosensitivity to cisplatin in human lung cancer cells. Our results indicated that the expression level of MAPK15 was positively correlated with cisplatin sensitivity through affecting the DNA repair capacity of cisplatin-treated cells. The expression of MAPK15 was transcriptionally regulated by the TNF-α-activated NF-κB signaling pathway, and TNF-α synergized with cisplatin, in a MAPK15-dependent manner, to exert cytotoxicity in vitro and in vivo. Therefore, levels of TNF-α dictate the responsiveness/sensitivity of lung cancer cells to cisplatin by transcriptionally upregulating MAPK15 to enhance chemosensitivity, suggesting manipulation of MAPK15 as a strategy to improve the therapeutic efficacy of chemotherapeutic drugs.

12.
Toxics ; 10(7)2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35878269

RESUMO

Smoking has been recognized by the World Health Organization (WHO) as the fifth highest threat to humanity. Smoking, a leading disease promoter, is a major risk factor for non-communicable diseases (NCDs) such as cancer, cardiovascular disease, diabetes, and chronic respiratory diseases. NCDs account for 63% of all deaths worldwide. Passive smoking is also a health risk. Globally, more than a third of all people are regularly exposed to harmful smoke. Air pollution is a common global problem in which pollutants emitted into the atmosphere undergo a series of physical or chemical reactions to produce various oxidation products, which are often referred to as secondary pollutants. Secondary pollutants include ozone (O3), sulfur trioxide (SO3), nitrogen dioxide (NO2), and respirable particulate matter (PM). It is worth mentioning that third-hand smoke (THS), formed by the reaction of nicotine with second-hand smoke (SHS) caused by indoor O3 or nitrous acid (HONO), is a major indoor secondary pollutant that cannot be ignored. As a form of indoor air pollution that is relatively difficult to avoid, THS exists in any corner of the environment where smokers live. In this paper, we summarize the important research progress on the main components, detection, and toxicity of THS and look forward to future research directions. Scientific understanding of THS and its hazards will facilitate smoking bans in indoor and public places and raise public concern for how to prevent and remove THS.

13.
Cancer Cell Int ; 22(1): 237, 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35897065

RESUMO

Epithelial cells can trans-differentiate into motile mesenchymal cells through a dynamic process known as epithelial-mesenchymal transition (EMT). EMT is crucial in embryonic development and wound healing but also contributes to human diseases such as organ fibrosis and cancer progression. Heavy metals are environmental pollutants that can affect human health in various ways, including causing cancers. The cytotoxicity and carcinogenicity of heavy metals are complex, and studies have demonstrated that some of these metals can affect the progress of EMT. Here, we focus on reviewing the roles of six environmentally common toxic metals concerning EMT: arsenic (AS), cadmium (Cd), cobalt (Co), chromium (Cr), nickel (Ni), and copper (Cu). Noteworthily, the effects of these elements on EMT may vary according to the form, dose, and exposure time; the dual role of heavy metals (e.g., AS, Cd, and Cu) on EMT is also observed, in which, sometimes they can promote while sometimes inhibit the EMT process. Given the vast number of toxicologically relevant metals that exist in nature, we believe a comprehensive understanding of their effects on EMT is required to dictate in what circumstances these metals act more likely as demons or angels.

14.
Int J Mol Sci ; 23(14)2022 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-35887201

RESUMO

Cytochrome P450 enzymes (CYP450s) exert mighty catalytic actions in cellular metabolism and detoxication, which play pivotal roles in cell fate determination. Preliminary data shows differential expression levels of CYP27C1, one of the "orphan P450s" in human lung cancer cell lines. Here, we study the functions of CYP27C1 in lung cancer progression and drug endurance, and explore its potential to be a diagnostic and therapeutic target for lung cancer management. Quantitative real-time PCR and immunoblot assays were conducted to estimate the transcription and protein expression level of CYP27C1 in human lung cancer cell lines, which was relatively higher in A549 and H1975 cells, but was lower in H460 cells. Stable CYP27C1-knockdown A549 and H1975 cell lines were established, in which these cells showed enhancement in cell proliferation, colony formation, and migration. In addition, aberrant IGF-1R/Akt/p53 signal transduction was also detected in stable CYP27C1-knockdown human lung cancer cells, which exhibited greater tolerance towards the treatments of anticancer agents (including vinorelbine, picropodophyllin, pacritinib, and SKLB610). This work, for the first time, reveals that CYP27C1 impacts lung cancer cell development by participating in the regulation of the IGF-1R/Akt/p53 signaling pathway, and the level of CYP27C1 plays indispensable roles in dictating the cellular sensitivity towards multiple anticancer agents.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Transdução de Sinais , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
15.
Cancer Cell Int ; 22(1): 212, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35698138

RESUMO

Nuclear factor of activated T-cells, cytoplasmic 4 (NFATc4), a transcription factor of NFAT family, which is activated by Ca2+/calcineurin signaling. Recently, it is reported that aberrantly activated NFATc4 participated and modulated in the initiation, proliferation, invasion, and metastasis of various cancers (including cancers of the lung, breast, ovary, cervix, skin, liver, pancreas, as well as glioma, primary myelofibrosis and acute myelocytic leukemia). In this review, we cover the latest knowledge on NFATc4 expression pattern, post-translational modification, epigenetic regulation, transcriptional activity regulation and its downstream targets. Furthermore, we perform database analysis to reveal the prognostic value of NFATc4 in various cancers and discuss the current unexplored areas of NFATc4 research. All in all, the result from these studies strongly suggest that NFATc4 has the potential as a molecular therapeutic target in multiple human cancer types.

16.
Int J Pharm ; 619: 121704, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35358643

RESUMO

Unpredictable outbreaks due to respiratory viral infections emphasize the need for new drug delivery strategies to the entire respiratory tract. As viral attack is not limited to a specific anatomic region, antiviral therapy that targets both the upper and lower respiratory tract would be most effective. This study aimed to formulate tamibarotene, a retinoid derivative previously reported to display broad-spectrum antiviral activity against influenza and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), as a novel dual particle size powder formulation that targets both the nasal cavity and the lung by a single route of intranasal administration. Spray freeze drying (SFD) and spray drying (SD) techniques were employed to prepare tamibarotene powder formulations, and cyclodextrin was used as the sole excipient to enhance drug solubility. With the employment of appropriate atomizing nozzles, particles of size above 10 µm and below 5 µm could be produced for nasal and lung deposition, respectively. The aerosol performance of the powder was evaluated using Next Generation Impactor (NGI) coupled with a glass expansion chamber and the powder was dispersed with a nasal powder device. By blending powder of two different particle sizes, a single powder formulation with dual aerosol deposition characteristic in both the nasal and pulmonary regions was produced. The aerosol deposition fractions in the nasal cavity and pulmonary region could be modulated by varying the powder mixing ratio. All dry powder formulations exhibited spherical structures, amorphous characteristics and improved dissolution profile as compared to the unformulated tamibarotene. Overall, a novel dual targeting powder formulation of tamibarotene exhibiting customizable aerosol deposition profile was developed. This exceptional formulation strategy can be adopted to deliver other antimicrobial agents to the upper and lower airways for the prevention and treatment of human respiratory infections.


Assuntos
Tratamento Farmacológico da COVID-19 , Inaladores de Pó Seco , Administração por Inalação , Administração Intranasal , Aerossóis , Antivirais , Humanos , Pulmão , Tamanho da Partícula , Pós , SARS-CoV-2
17.
Toxics ; 10(2)2022 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-35202237

RESUMO

Since the rise and rapid development of nanoscale science and technology in the late 1980s, nanomaterials have been widely used in many areas including medicine, electronic products, crafts, textiles, and cosmetics, which have provided a lot of convenience to people's life. However, while nanomaterials have been fully utilized, their negative effects, also known as nano pollution, have become increasingly apparent. The adverse effects of nanomaterials on the environment and organisms are mainly based on the unique size and physicochemical properties of nanoparticles (NPs). NPs, as the basic unit of nanomaterials, generally refer to the ultrafine particles whose spatial scale are defined in the range of 1-100 nm. In this review, we mainly introduce the basic status of the types and applications of NPs, airborne NP pollution, and the relationship between airborne NP pollution and human diseases. There are many sources of airborne NP pollutants, including engineered nanoparticles (ENPs) and non-engineered nanoparticles (NENPs). The NENPs can be further divided into those generated from natural activities and those produced by human activities. A growing number of studies have found that exposure to airborne NP pollutants can cause a variety of illnesses, such as respiratory diseases, cardiovascular diseases, and neurological disorders. To deal with the ever increasing numbers and types of NPs being unleashed to the air, we believe that extensive research is needed to provide a comprehensive understanding of NP pollution hazards and their impact mechanisms. Only in this way can we find the best solution and truly protect the safety and quality of life of human beings.

18.
J Cancer Res Clin Oncol ; 148(11): 3145-3162, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35066671

RESUMO

PURPOSE: Acetyl-CoA Carboxylases (ACCs) are key fatty acid metabolic enzymes responsible for catalyzing the carboxylation of acetyl-CoA to malonyl-CoA. The role of ACC1 has been associated with tumor biology, but the role of ACC2 in cancer remains largely uncharacterized. METHODS: We conducted a transcriptomic analysis using GEPIA and Oncomine to study the expression of ACC2 in different cancers. Immunohistochemistry was used to examine the expression of ACC2 in lung cancer tissue microarray, and the correlation between ACC2 expression and clinical parameters was analyzed. Following ACC2 knockdown by RNA interference in A549 and HCC827 cells, Cell Counting Kit­8 and transwell assays were used to detect cell proliferation and migration. Real-time PCR was used to detect cell cycle-related genes in A549 cells. GEO dataset and KM-plotter database were used to analyze the relationship between ACC2 expression and the prognosis in lung cancer patients. RESULTS: We found that ACC2 is under-expressed in cancerous tissue and the expression of ACC2 is negatively correlated with tumor size, regional lymph-node metastases, and clinical stage of lung adenocarcinoma patients. In addition, knocking down ACC2 in A549 cells and HCC827 cells can promote cell proliferation and migration, and cell cycle-related genes MAD2L1 and CCNB2 were up-regulated after ACC2 was knockdown in A549 cells. Finally, we found that lung adenocarcinoma patients with under-expressed ACC2 have a worse prognosis. CONCLUSIONS: Our results suggest that ACC2 is a potential diagnostic and prognostic marker that negatively correlated with clinical outcomes in lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Acetilcoenzima A , Acetil-CoA Carboxilase/química , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Adenocarcinoma de Pulmão/genética , Ácidos Graxos/metabolismo , Humanos , Neoplasias Pulmonares/genética
19.
Int J Mol Sci ; 24(1)2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36613552

RESUMO

The cytochrome P450s (CYP450s) include key oxidative enzymes involved in the metabolism of various carcinogens and anticancer drugs. Bioinformatic studies have demonstrated the association of CYP3A43 with liver cancer and ovarian cancer. However, the biological function of CYP3A43 in tumor progression remains unclear. To further reveal the role of CYP3A43 in tumor progression, we first analyzed the data from the UALCAN database and found that CYP3A43 was negatively correlated to the cancer staging and lymph node metastasis of lung adenocarcinoma (LUAD). We established stable CYP3A43-knockdown LUAD H1299 cell line and found that its knockdown enhanced cell proliferation, colony formation, and migration in vitro, and promoted the growth of tumor xenograft in vivo. Interestingly, when CYP3A43 was ectopically-expressed in the LUAD cell lines, decreased cell proliferation and ERK1/2 phosphorylation level were observed. Lastly, we also identified CYP3A43 co-expressed genes in LUAD from LinkedOmics database followed by GO and KEGG analyses. In conclusion, our results indicate the unprecedented role of CYP3A43 in the suppression of LUAD and provide new possibilities for targeted therapy of this life-threatening disease.


Assuntos
Adenocarcinoma de Pulmão , Hidrocarboneto de Aril Hidroxilases , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/metabolismo , Hidrocarboneto de Aril Hidroxilases/genética
20.
Molecules ; 26(24)2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34946594

RESUMO

Moringa oleifera (M. oleifera), which belongs to the Moringaceae family, is a common herb, rich in plant compounds. It has a variety of bioactive compounds that can act as antioxidants, antibiotics, anti-inflammatory and anti-cancer agents, etc., which can be obtained in different body parts of M. oleifera. Isothiocyanates (ITCs) from M. oleifera are one class of these active substances that can inhibit cancer proliferation and promote cancer cell apoptosis through multiple signaling pathways, thus curbing cancer migration and metastasis, at the same time they have little adverse effect on normal cells. There are multiple variants of ITCs in M. oleifera, but the predominant phytochemical is 4-(α-L-rhamnosyloxy)benzyl isothiocyanate, also known as moringa isothiocyanate (MIC-1). Studies have shown that MIC-1 has the possibility to be used clinically for the treatment of diabetes, neurologic diseases, obesity, ulcerative colitis, and several cancer types. In this review, we focus on the molecular mechanisms underlying the anti-cancer and anti-chronic disease effects of MIC-1, current trends, and future direction of MIC-1 based treatment strategies. This review combines the relevant literature of the past 10 years, in order to provide more comprehensive information of MIC-1 and to fully exploit its potentiality in the clinical settings.


Assuntos
Anti-Inflamatórios/farmacologia , Fármacos Antiobesidade/farmacologia , Antiulcerosos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Hipoglicemiantes/farmacologia , Isotiocianatos/farmacologia , Anti-Inflamatórios/química , Fármacos Antiobesidade/química , Antiulcerosos/química , Antineoplásicos Fitogênicos/química , Humanos , Hipoglicemiantes/química , Isotiocianatos/química , Moringa oleifera/química
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