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1.
Carcinogenesis ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39023209

RESUMO

Since gastric cancer shows no apparent signs in its early stages, most patients are diagnosed later with a poor prognosis. We therefore seek more sensitive and specific GC biomarkers. Small RNAs formed from tRNAs represent a novel class of non-coding RNAs that are highly abundant in bodily fluids and essential to biological metabolism. This study explores the potential of i-tRF-AsnGTT in gastric cancer diagnostics. To begin with, we sequenced i-tRF-AsnGTT using high-throughput methods. i-tRF-AsnGTT expression levels in GC were determined using real-time fluorescence PCR. Agarose gel electrophoresis, Sanger sequencing, and repeated freezing and thawing were performed to verify molecular properties. A correlation was found between clinical and pathological parameters and i-tRF-AsnGTT expression levels through the χ² test, and ROC was used to analyze its diagnostic value in GC. In serum, i-tRF-AsnGTT has a low and stable expression level. It can differentiate between patients with gastric cancer and gastritis and healthy donors with better diagnostic efficacy. In combination with clinicopathological parameters, i-tRF-AsnGTT correlates with tumor differentiation, infiltration depth of tumors, TNM stage, lymph node metastases, and neural/vascular invasion. Serum i-tRF-AsnGTT expression is low in GC patients. Serum from postoperative patients shows increased i-tRF-AsnGTT expression levels. Potentially, this could be used as a biomarker to help diagnose gastric cancer and monitor its prognosis.

2.
Cell Mol Biol Lett ; 29(1): 95, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956466

RESUMO

BACKGROUND: An increasing number of studies have demonstrated the association of circular RNAs (circRNAs) with the pathological processes of various diseases and their involvement in the onset and progression of multiple cancers. Nevertheless, the functional roles and underlying mechanisms of circRNAs in the autophagy regulation of gastric cancer (GC) have not been fully elucidated. METHODS: We used transmission electron microscopy and the mRFP-GFP-LC3 dual fluorescent autophagy indicator to investigate autophagy regulation. The cell counting kit-8 assay, colony formation assay, 5-ethynyl-2'-deoxyuridine incorporation assay, Transwell assay, and Western blot assay were conducted to confirm circPTPN22's influence on GC progression. Dual luciferase reporter assays validated the binding between circPTPN22 and miR-6788-5p, as well as miR-6788-5p and p21-activated kinase-1 (PAK1). Functional rescue experiments assessed whether circPTPN22 modulates PAK1 expression by competitively binding miR-6788-5p, affecting autophagy and other biological processes in GC cells. We investigated the impact of circPTPN22 on in vivo GC tumors using a nude mouse xenograft model. Bioinformatics tools predicted upstream regulatory transcription factors and binding proteins of circPTPN22, while chromatin immunoprecipitation and ribonucleoprotein immunoprecipitation assays confirmed the binding status. RESULTS: Upregulation of circPTPN22 in GC has been shown to inhibit autophagy and promote cell proliferation, migration, and invasion. Mechanistically, circPTPN22 directly binds to miR-6788-5p, subsequently regulating the expression of PAK1, which activates protein kinase B (Akt) and extracellular signal-regulated kinase (Erk) phosphorylation. This modulation ultimately affects autophagy levels in GC cells. Additionally, runt-related transcription factor 1 (RUNX1) negatively regulates circPTPN22 expression, while RNA-binding proteins such as FUS (fused in sarcoma) and ELAVL1 (recombinant ELAV-like protein 1) positively regulate its expression. Inhibition of the autophagy pathway can increase FUS expression, further upregulating circPTPN22 in GC cells, thereby exacerbating the progression of GC. CONCLUSION: Under the regulation of the transcription factor RUNX1 and RNA-binding proteins FUS and ELAVL1, circPTPN22 activates the phosphorylation of Akt and Erk through the miR-6788-5p/PAK1 axis, thereby modulating autophagy in GC cells. Inhibition of autophagy increases FUS, which in turn upregulates circPTPN22, forming a positive feedback loop that ultimately accelerates the progression of GC.


Assuntos
Autofagia , Movimento Celular , Proliferação de Células , Subunidade alfa 2 de Fator de Ligação ao Core , Proteína Semelhante a ELAV 1 , MicroRNAs , RNA Circular , Proteína FUS de Ligação a RNA , Neoplasias Gástricas , Quinases Ativadas por p21 , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Autofagia/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Quinases Ativadas por p21/metabolismo , Quinases Ativadas por p21/genética , Proliferação de Células/genética , Proteína FUS de Ligação a RNA/metabolismo , Proteína FUS de Ligação a RNA/genética , Movimento Celular/genética , Linhagem Celular Tumoral , Animais , Proteína Semelhante a ELAV 1/metabolismo , Proteína Semelhante a ELAV 1/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Camundongos , Invasividade Neoplásica , Camundongos Endogâmicos BALB C
3.
Acta Biochim Biophys Sin (Shanghai) ; 56(6): 927-936, 2024 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-38686459

RESUMO

Non-small cell lung cancer (NSCLC) is one of the most prevalent cancers in the world, and early diagnosis can effectively improve patient survival. Here, differentially expressed circIARS genes are screened from the sequencing results, and their molecular characteristics are examined by Sanger sequencing, RNase R assay, agarose gel electrophoresis (AGE), and fluorescence in situ hybridization (FISH). Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) is performed to detect the expression level of circIARS. The diagnostic value of the signature is analyzed using a subject operating characteristic (ROC) curve. Moreover, plasma is collected from postsurgical, chemotherapy, and relapse patients to investigate the prognostic value of circIARS in NSCLC. The expression of circIARS is greater in both the plasma and tissues of NSCLC patients than in those of healthy individuals, and could be used to distinguish NSCLC patients from patients with benign pulmonary disease (BPD), small cell lung cancer (SCLC) patients, and healthy individuals. The expression level of circIARS relatively decreases after antitumor therapy, such as chemotherapy, and relatively increases after recurrence. ROC analysis reveals that circIARS has better detection efficiency than traditional markers. In addition, circIARS expression level is strongly correlated with several clinicopathological parameters. Finally, we tentatively predict the downstream miRNAs or RBP that might bind to circIARS. Plasma circIARS is significantly greater in NSCLC patients and has good stability and specificity as a diagnostic marker, which could aid in the adjuvant diagnosis and dynamic monitoring of NSCLC.


Assuntos
Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Feminino , Masculino , Pessoa de Meia-Idade , Prognóstico , Regulação Neoplásica da Expressão Gênica , RNA Circular/sangue , RNA Circular/genética , Idoso
4.
Mol Carcinog ; 62(10): 1504-1517, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37314123

RESUMO

Gastric cancer (GC) is a common malignant digestive system tumor. Since the early symptoms of GC are usually vague and the positive rate of common biomarkers of GC is low, it is of urgent need to find new biomarkers with good sensitivity and specificity to screen and diagnose GC patients. The tRNA-derived small RNAs (tsRNAs) are emerging small noncoding RNAs that play an essential role in cancer progression. In this study, we explored whether novel tsRNAs have the potential to serve as biomarkers for GC. Three tsRNAs significantly upregulated in GC were screened by the tsRFun database. The expression level of tRF-29-R9J8909NF5JP was detected by real-time fluorescence quantitative polymerase chain reaction. Agarose gel electrophoresis and Sanger sequencing were used to verify the characteristics of tRF-29-R9J8909NF5JP. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of tRF-29-R9J8909NF5JP. The χ2 test was used to analyze the correlation between tRF-29-R9J8909NF5JP expression level and clinicopathological parameters. Kaplan-Meier survival curves were used to analyze the correlation between tRF-29-R9J8909NF5JP expression levels and survival time of GC patients. In this study, the expression level of tRF-29-R9J8909NF5JP was significantly increased in GC tissues. The expression level of tRF-29-R9J8909NF5JP was considerably higher in the serum of GC patients than in the serum of gastritis patients and in the serum of healthy donors, and the expression level of tRF-29-R9J8909NF5JP was significantly decreased in the serum of GC patients after surgery. In addition, the χ2 test showed that the expression level of tRF-29-R9J8909NF5JP in GC serum was correlated with differentiation grade, T-stage, lymph node metastasis, tumor node metastasis stage, and neurological/vascular invasion. The results of the survival curve showed that the high expression of serum tRF-29-R9J8909NF5JP was associated with a low survival rate. ROC analysis showed that serum tRF-29-R9J8909NF5JP had higher diagnostic efficiency than common GC biomarkers, and the diagnostic efficiency was further improved by combining them. At the end of the study, we predicted the downstream of tRF-29-R9J8909NF5JP. The expression level of tRF-29-R9J8909NF5JP in the serum of GC patients can effectively identify GC patients and has higher efficacy than conventional biomarkers. In addition, serum tRF-29-R9J8909NF5JP can monitor the postoperative condition of GC patients, suggesting that it has the potential to become a biomarker for GC.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Prognóstico , Biomarcadores Tumorais/metabolismo , Curva ROC , Metástase Linfática
5.
J Transl Med ; 21(1): 514, 2023 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-37516888

RESUMO

Programmed cell death (PCD) plays an important role in many aspects of individual development, maintenance of body homeostasis and pathological processes. Ferroptosis is a novel form of PCD characterized by the accumulation of iron-dependent lipid peroxides resulting in lethal cell damage. It contributes to tumor progression in an apoptosis-independent manner. In recent years, an increasing number of non-coding RNAs (ncRNAs) have been demonstrated to mediate the biological process of ferroptosis, hence impacting carcinogenesis, progression, drug resistance, and prognosis. However, the clear regulatory mechanism for this phenomenon remains poorly understood. Moreover, ferroptosis does not usually exist independently. Its interaction with PCD, like apoptosis, necroptosis, autophagy, pyroptosis, and cuproptosis, to destroy cells appears to exist. Furthermore, ncRNA seems to be involved. Here, we review the mechanisms by which ferroptosis occurs, dissect its relationship with other forms of death, summarize the key regulatory roles played by ncRNAs, raise relevant questions and predict possible barriers to its application in the clinic, offering new ideas for targeted tumour therapy.


Assuntos
Ferroptose , Neoplasias , Humanos , Ferroptose/genética , Apoptose/genética , Neoplasias/genética , Carcinogênese , Piroptose , RNA não Traduzido/genética
6.
Exp Cell Res ; 415(1): 113113, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35339472

RESUMO

Despite significant progress in the treatment of myeloma, multiple myeloma (MM) remains an incurable hematological malignancy due to cell adhesion-mediated drug resistance (CAM-DR) phenotype. However, data on the molecular mechanisms underlying the CAM-DR remains scanty. Here, we identified a miRNA-mRNA regulatory network in myeloma cells that are directly adherent to bone marrow stromal cells (BMSCs). Our data showed that the BMSCs up-regulated miR-30a-5p and down-regulated BCL2L11 at both mRNA and protein level in the myeloma cells. Besides, luciferase reporter genes demonstrated direct interaction between miR-30a-5p and BCL2L11 gene. Moreover, the BMSCs activated NF-ΚB signaling pathway in myeloma cells and the NF-κB P65 was shown to directly bind the miR-30a-5p promoter region. Moreover, suppression of the miR-30a-5p or upregulation of the BCL2L11 promoted apoptosis of the myeloma cells independent of the BMSCs, thus suggesting clinical significance of miR-30a-5p inhibitor and PLBCL2L11 plasmid in CAM-DR. Together, our data demonstrated the role of P65-miR-30a-5p-BCL2L11 loop in CAM-DR myeloma cells. These findings give new insights into the role of tumor microenvironment in the treatment of patients with myeloma.


Assuntos
MicroRNAs , Mieloma Múltiplo , Proteína 11 Semelhante a Bcl-2/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Mieloma Múltiplo/genética , NF-kappa B/metabolismo , RNA Mensageiro , Microambiente Tumoral/genética
7.
Int J Med Sci ; 20(9): 1189-1201, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37575270

RESUMO

Objective: Gastric cancer (GC) has high morbidity and mortality due to inefficient early screening. Therefore, we are searching for more sensitive and specific diagnostic markers for GC. tRNA-derived small RNAs are novel non-coding small RNAs with good abundance and stable presence in body fluids, which may play multiple biological regulatory roles. In this study, we aimed to find a potential biomarker with high accuracy in tRNA-derived small RNAs that can help diagnose GC. Methods: tRF-27-FDXXE6XRK45 was screened as a target molecule by high-throughput sequencing in three pairs of GC tissues. RNA quantitative reverse transcription PCR was conducted to detect the expression levels of tRF-27-FDXXE6XRK45. Agarose gel electrophoresis, Sanger sequencing, cytoplasmic and nuclear RNA isolation assays, gradient dilution experiments, and room temperature and repeated freeze-thaw experiments were used to assess the detection performance of tRF-27-FDXXE6XRK45. Using the chi-square test to analyze the correlation between tRF-27-FDXXE6XRK45 expression levels and clinicopathological parameters. In addition, receiver operating characteristic curves were used to evaluate the diagnostic value of tRF-27-FDXXE6XRK45 in GC. Results: tRF-27-FDXXE6XRK45 expression levels, significantly upregulated in tissues and sera of GC patients and decreased after radical GC surgery, were correlated with the degree of differentiation, depth of tumor infiltration, TNM stage, lymph node metastasis, and nerve/vascular invasion. In comparison with current GC diagnostic markers, tRF-27-FDXXE6XRK45 displayed better efficacy. Conclusions: tRF-27-FDXXE6XRK45, with high diagnostic efficacy, can distinguish GC patients from gastritis patients and healthy donors, suggesting that tRF-27-FDXXE6XRK45 may be a promising candidate as a diagnostic marker for GC.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Biomarcadores , RNA , RNA de Transferência/genética , Reação em Cadeia da Polimerase
8.
Clin Lab ; 69(8)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37560875

RESUMO

BACKGROUND: Blood count reference intervals are important to diagnose diseases and assess overall health, especially for young children. Although, in 2021, the National Health Commission of the People's Republic of China issued "Reference intervals of blood cell analysis for children (WS/T 779-2021)", these RIs may not suitable for small children all over the country due to racial, lifestyle, and geographical differences. The aim of this study was to establish and validate locally determined hematological reference intervals among young children in Nantong district and compare them with WS/T 779-2021 and American data. METHODS: The reference sample consisted of 4,758 apparently healthy small children aged from age 28 days to 3 years according to the EP28-A3c guideline issued by the Clinical and Laboratory Standards Institute (CLSI). Capillary blood samples collected in K2-EDTA anticoagulant tubes analyzed by standard procedures. Statistical analysis was based on the guidelines of the CLSI. RESULTS: Pediatric reference intervals for 18 capillary complete blood count (CCBC) parameters were established for young children. WBC and differentials did not differ by gender in the combined analysis of all data, but showed some variations among different age groups, especially for NE and LYM. RIs of RBC value, MCV, and MCH were established, especially with regard to the difference among different age and gender groups. An overall increasing trend of PLT value was observed in children with no obvious difference between boys and girls. Further validation with 1,136 healthy subjects demonstrated that the verified proportions of our study were within 90.11% - 100%. RIs determined in the present study were more concentrated than WS/T 779-2021, with slight differences in the upper and bottom boundaries. CONCLUSIONS: Establishing appropriate region-specific reference intervals for pediatrics is essential. This study offers local reference intervals of CCBC values for young children and could be used as a benchmark for similar populations in the Yangtze River Delta economic region.


Assuntos
Testes Hematológicos , Masculino , Feminino , Humanos , Criança , Pré-Escolar , Adulto , Valores de Referência , Contagem de Células Sanguíneas , Padrões de Referência , China
9.
J Med Genet ; 59(7): 623-631, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35145038

RESUMO

Most small non-coding RNAs (sncRNAs) with regulatory functions are encoded by majority sequences in the human genome, and the emergence of high-throughput sequencing technology has greatly expanded our understanding of sncRNAs. sncRNAs are composed of a variety of RNAs, including tRNA-derived small RNA (tsRNA), small nucleolar RNA (snoRNA), small nuclear RNA (snRNA), PIWI-interacting RNA (piRNA), etc. While for some, sncRNAs' implication in several pathologies is now well established, the potential involvement of tsRNA, snoRNA, snRNA and piRNA in human diseases is only beginning to emerge. Recently, accumulating pieces of evidence demonstrate that tsRNA, snoRNA, snRNA and piRNA play an important role in many biological processes, and their dysregulation is closely related to the progression of cancer. Abnormal expression of tsRNA, snoRNA, snRNA and piRNA participates in the occurrence and development of tumours through different mechanisms, such as transcriptional inhibition and post-transcriptional regulation. In this review, we describe the research progress in the classification, biogenesis and biological function of tsRNA, snoRNA, snRNA and piRNA. Moreover, we emphasised their dysregulation and mechanism of action in cancer and discussed their potential as diagnostic and prognostic biomarkers or therapeutic targets.


Assuntos
Neoplasias , Pequeno RNA não Traduzido , Regulação da Expressão Gênica , Humanos , Neoplasias/genética , RNA Interferente Pequeno/genética , RNA Nucleolar Pequeno/genética , Pequeno RNA não Traduzido/genética
10.
Mol Med ; 28(1): 63, 2022 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-35690737

RESUMO

BACKGROUND: Gastric cancer (GC) is one of the diseases that endanger human health with high morbidity and mortality. The positive rates of traditional biomarkers in the diagnosis of GC are low, so it is necessary to find biomarkers with high sensitivity to increase the detection rate. tRNA-derived small RNAs (tsRNAs) are novel small non-coding RNAs with specific biological functions and aberrant expression in cancer. In this study, we focused on the potential of tRNA-derived small RNAs as GC biomarkers. METHODS: The differentially expressed tsRNAs in three pairs of GC tissues were screened with high-throughput sequencing and verified using the TCGA database and Quantitative real-time PCR. The methodological evaluation of tRF-23-Q99P9P9NDD was verified by agarose gel electrophoresis, RIN evaluation, and Sanger sequencing. The Chi-square test was used to evaluate the relationship between the tRF-23-Q99P9P9NDD expression and clinicopathological parameters. Kaplan-Meier survival analysis was used to evaluate the effect of the tRF-23-Q99P9P9NDD expression on survival. Additionally, the receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of tRF-23-Q99P9P9NDD in GC. RESULTS: Differential expression of serum tRF-23-Q99P9P9NDD could distinguish GC patients from gastritis patients and healthy donors. Chi-square test showed that high expression of tRF-23-Q99P9P9NDD was significantly associated with T stage, lymph node metastasis, TNM stage, and nerve/vascular invasion. Kaplan-Meier curve showed that patients with high expression of tRF-23-Q99P9P9NDD had a lower survival rate than patients with low expression of this biomarker. ROC analysis showed that, compared with conventional biomarkers, the efficacy of tRF-23-Q99P9P9NDD was higher, which was improved by the combination of biomarkers, and even in the early stages. Finally, we preliminarily predicted the downstream of tRF-23-Q99P9P9NDD in GC cells. CONCLUSIONS: The expression of tRF-23-Q99P9P9NDD in GC serum can identify GC patients, and it has higher efficacy than conventional biomarkers even in the early stages. Furthermore, tRF-23-Q99P9P9NDD can monitor the postoperative conditions of GC patients.


Assuntos
Neoplasias Gástricas , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Estimativa de Kaplan-Meier , RNA de Transferência/metabolismo , Curva ROC , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética
11.
Mol Med ; 28(1): 79, 2022 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-35836125

RESUMO

Circular RNAs (circRNAs) have become a research hotspot in recent years with their universality, diversity, stability, conservativeness, and spatiotemporal specificity. N6-methyladenosine (m6A), the most abundant modification in the eukaryotic cells, is engaged in the pathophysiological processes of various diseases. An increasing amount of evidence has suggested that m6A modification is common in circRNAs and is associated with their biological functions. This review summarizes the effects of m6A modification on circRNAs and their regulation mechanisms in cancers, providing some suggestions of m6A-modified circRNAs in cancer therapy.


Assuntos
Neoplasias , RNA Circular , Humanos , Neoplasias/genética , RNA Circular/genética
12.
Exp Cell Res ; 408(2): 112870, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34648843

RESUMO

Multiple myeloma (MM) is an incurable plasma cell malignancy. The progression of MM is closely related to the bone microenvironment. Bone matrix proteins are remodeled and manipulated to govern cancer growth during the process of MM. However the role of normal bone extracellular matrix in MM is still unclear. In this study the decellularized extracellular matrix derived from normal SD rats' skulls (N-dECM) was prepared by decellularization technology. The CCK 8 assay and the dead-live cell kit assay were used to determine the viability of MM cells and the sensitivity to bortezomib. The Realtime PCR and Western blot assay were used to assay the mRNA and protein related to MM. Under the treatment of N-dECM, we found that the viability of MM cells was inhibited and the sensitivity of MM cells to bortezomib was increased. Additionally, the expression levels of APRIL and TACI, which participated in the progression of MM, were significantly decreased in MM cells. It suggested that N-dECM might inhibit the development of MM via APRIL-TACI axis, and our study may provide a novel and potential biomaterial for MM therapy.


Assuntos
Materiais Biocompatíveis/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Matriz Extracelular/genética , Mieloma Múltiplo/tratamento farmacológico , Animais , Materiais Biocompatíveis/química , Osso e Ossos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Matriz Extracelular/química , Humanos , Ratos , Ratos Sprague-Dawley , Crânio/química , Engenharia Tecidual
13.
Mol Med ; 27(1): 94, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34445958

RESUMO

Circular RNAs (circRNAs), a novel type of non-coding RNAs (ncRNAs), have a covalently closed circular structure resulting from pre-mRNA back splicing via spliceosome and ribozymes. They can be classified differently in accordance with different criteria. As circRNAs are abundant, conserved, and stable, they can be used as diagnostic markers in various diseases and targets to develop new therapies. There are various functions of circRNAs, including sponge for miR/proteins, role of scaffolds, templates for translation, and regulators of mRNA translation and stability. Without m7G cap and poly-A tail, circRNAs can still be degraded in several ways, including RNase L, Ago-dependent, and Ago-independent degradation. Increasing evidence indicates that circRNAs can be modified by N-6 methylation (m6A) in many aspects such as biogenesis, nuclear export, translation, and degradation. In addition, they have been proved to play a regulatory role in the progression of various cancers. Recently, methods of detecting circRNAs with high sensitivity and specificity have also been reported. This review presents a detailed overview of circRNAs regarding biogenesis, biomarker, functions, degradation, and dynamic modification as well as their regulatory roles in various cancers. It's particularly summarized in detail in the biogenesis of circRNAs, regulation of circRNAs by m6A modification and mechanisms by which circRNAs affect tumor progression respectively. Moreover, existing circRNA detection methods and their characteristics are also mentioned.


Assuntos
Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , RNA Circular , Animais , Suscetibilidade a Doenças , Humanos , Metilação , MicroRNAs/genética , MicroRNAs/metabolismo , Técnicas de Diagnóstico Molecular , Neoplasias/diagnóstico , Neoplasias/terapia , Biossíntese de Proteínas , Estabilidade de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcrição Gênica
14.
Cancer Cell Int ; 21(1): 44, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33430866

RESUMO

BACKGROUND: Gastric cancer (GC) is one of the most common cancers in the world. Due to the lack of specific symptoms, more than 80% of patients are diagnosed as the advanced stage with a high mortality rate, so the early diagnosis of GC is incredibly essential. Circular RNAs (CircRNAs) are a kind of endogenous non-coding RNA with stable structure, the long half-life, and tumor specificity. It can be used as a diagnostic marker for tumors. METHOD: Using circRNA sequencing technology screened three pairs of GC and adjacent tissues, and circRNAs with significant expression differences were screened out. The circular structure and characteristics of circPTPN22 were determined by RT-qPCR, agarose gel electrophoresis, Sanger sequencing, RNase R, and actinomycin D assays. Cell Counting Kit-8, colony formation, Transwell, Wound healing, tumor formation in mice and western blotting assays were used to detect the effects of circPTPN22 on the proliferation, invasion, migration, tumor growth of GC cells in vitro and protein expression. RESULT: CircPTPN22 is up-regulated and positively correlated with metastasis in GC tissues, cells, and plasma. RT-qPCR results showed that circPTPN22 had good diagnostic efficacy and could be used to predict the prognosis of GC patients. In vitro and vivo experiments showed that the downregulation of circPTPN22 could inhibit cell proliferation, migration, and invasion through the epithelial-mesenchymal transformation (EMT) pathway. CircPTPN22 may regulate GC progression through the competitive binding of miRNAs. CONCLUSION: CircPTPN22 can be used as a potential diagnostic and prognostic marker for GC and can inhibit cell proliferation and metastasis through the competitive binding of miRNA to inhibit the EMT pathway.

15.
Future Oncol ; 17(8): 907-919, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33533649

RESUMO

Gastric cancer (GC) is one of the common malignant tumors with high mortality. The abundance of miRNAs in serum exosomes has proved to have a high application value as a new noninvasive diagnostic method. The purpose of this study was to investigate whether serum exosomal miR-92a-3p could be used as a new biomarker for early diagnosis of GC and evaluate its clinical application value by detecting the expression of serum exosomal miR-92a-3p in 131 patients with primary GC and 122 healthy controls by real-time quantitative (qRT)-PCR. The results showed that the expression level of serum exosomal miR-92a-3p in GC patients was significantly lower than that in normal controls (p < 0.0001). In addition, the level was closely correlated with lymph node metastasis and tumor node metastasis stage of GC patients. The area under the curve for serum exosomal miR-92a-3p was 0.829, significantly higher than for other indicators. Furthermore, combined detection of serum exosomal miR-92a-3p, CEA and CA19-9 was more sensitive than any of the three alone or any pair. These results showed that serum exosomal miR-92a-3p could be used as a novel new tumor biomarker to improve diagnostic efficiency in GC.


Assuntos
Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer/métodos , MicroRNAs/sangue , Neoplasias Gástricas/diagnóstico , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Linhagem Celular Tumoral , Exossomos/metabolismo , Estudos de Viabilidade , Feminino , Voluntários Saudáveis , Humanos , Biópsia Líquida/métodos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Neoplasias Gástricas/sangue , Neoplasias Gástricas/genética
16.
BMC Cardiovasc Disord ; 21(1): 429, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507544

RESUMO

BACKGROUND: Homocysteine (Hcy) is considered to be a risk factor for cardiovascular and cerebrovascular diseases. Few studies have evaluated the distribution of Hcy on a large-scale health examination. Accordingly, this study aimed to investigate the level and distribution of Hcy in the population with healthy physical examination and the correlation with other biomarkers, and analyzed for cardiovascular and other diseases. METHODS: Measurements of serum Hcy, TC, TG, LDL-c, HDL-c, ALT, ALP, γ-GT, TBIL, GLU, urea, Cr, UA, and related metabolic risk factors were selected for analysis from 8063 medical examination samples collected from February 2017 to April 2020. The relationship between Hcy and other biochemical indicators were evaluated with the multivariate regression model of age, gender, smoking, drinking, body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP). RESULTS: Among 8063 cases, the age, BMI, SBP, and DBP of the high-Hcy group were higher than those of the low-Hcy group, the difference was statistically significant (P < 0.001), and the proportion of males, smoking, and drinking were higher than the low-Hcy group, the difference was statistically significant (P < 0.001); Hcy of the abnormal GLU group is higher than the normal GLU group (P = 0.002) and the Hcy of abnormal TG and HDL is higher than that of the normal blood lipid group (P < 0.001); Hcy of people with abnormal UA and Urea was higher than that of people with normal renal function (P < 0.001, P = 0.007). In multivariate analysis, lnHDL-C was negatively correlated with lnHcy (ß = - 0.038, SE = 0.016, P = 0.019), lnCr was positively correlated with lnHcy (ß = 0.055, SE = 0.016, P < 0.001), lnUA and lnHcy were positive correlated (ß = 0.043, SE = 0.019, P = 0.022). CONCLUSION: Hcy is closely related to HDL-c, Cr, and UA, which indicates that Hcy may affect the metabolism of HDL-c and UA, and can also be used as an auxiliary diagnostic index for kidney injury.


Assuntos
Doenças Cardiovasculares/sangue , Homocisteína/sangue , Hiper-Homocisteinemia/sangue , Adulto , Fatores Etários , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , HDL-Colesterol/sangue , Creatinina/sangue , Feminino , Voluntários Saudáveis , Humanos , Hiper-Homocisteinemia/diagnóstico , Hiper-Homocisteinemia/epidemiologia , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Fatores Sexuais , Ácido Úrico/sangue , Adulto Jovem
17.
Clin Lab ; 67(2)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33616336

RESUMO

BACKGROUND: Systematic performance verification is required before a laboratory can introduce a new measure-ment procedure for reporting results of patient testing. The aim of this study was to explore the basic performance and clinical application value of KU-F10 Feces analyzer. METHODS: We collected 530 fecal specimens in our hospital from October 2019 to February 2020, using manual methods as the gold standard. Then we made a comprehensive evaluation from repeatability, carried pollution rate, coincidence rate of formed element, and coincidence rate of fecal occult blood test. RESULTS: The sensitivity of white blood cells was 90.3%, the specificity was 99.2%, and the coincidence rate with microscopy was 98.7%; the sensitivity of the instrument to detect red blood cells was 90.3%, the specificity was 98.2%, and the coincidence rate with microscopy was 97.7%, The sensitivity of the instrument to detect fungi is 100.0%, the specificity is 98.7%, and the coincidence rate with the microscopy is 98.7%. The sensitivity of the in-strument to detect fat globules is 94.7%, the specificity is 99.0%, the coincidence rate with the microscopy is 98.9%. Comparison of instrumental fecal occult blood test and reagent B fecal occult blood result: On the 387 cases tested fecal samples, the sensitivity of the instrument was 83.8%, the specificity was 96.5%, and the coincidence rate with the results of microscopy was 92.3%. FOB minimum detection limit is 0.1 µg/mL and detection range is 0.1 to 2,000 µg/mL. CONCLUSIONS: The KU-F10 feces analyzer has an advantage of a high degree of automation, simple operation procedures, fast detection speed, improved working environment, improved work efficiency, and higher clinical application value.


Assuntos
Neoplasias Colorretais , Automação , Fezes , Humanos , Leucócitos , Sangue Oculto , Sensibilidade e Especificidade
18.
J Cell Mol Med ; 24(6): 3492-3503, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32048803

RESUMO

Loss of one or some specific miRNA-mediated regulation is closely associated with malignant progression of multiple myeloma (MM). But how these miRNAs work and what role the specific miRNA plays in this process of malignant progression remain unclear. It was found in this study that the expression of miR-129 was decreased in both MM cell lines and newly diagnosed MM patients. Further clinicopathological statistics showed that miR-129 was correlated with the isotype of MM patients. MiR-129 overexpression disturbed cell proliferation, cell cycle evolution and spurred apoptosis both in vitro and in vivo. MAP3K7, a kinase able to activate NF-κB circuit, was found to be up-regulated in MM and contain a binding target of miR-129. In addition, lncRNA PCAT-1 functioned to sponge miR-129 and thereby lowered its expression. PCAT-1 knockdown eliminated the tumour-promoting effect caused by miR-129 inhibition, probably through repressing MAP3K7 and subsequent NF-κB activation. To the best of our knowledge, this is the first study to have discovered that increased expression of PCAT-1 could augment cell proliferation and cycle procession and inhibit apoptosis by down-regulating miR-129 via the MAP3K7/NF-κB pathway in MM.


Assuntos
MAP Quinase Quinase Quinases/metabolismo , MicroRNAs/metabolismo , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , NF-kappa B/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Apoptose/genética , Sequência de Bases , Pontos de Checagem do Ciclo Celular/genética , Divisão Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Camundongos Nus , MicroRNAs/sangue , MicroRNAs/genética , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Ligação Proteica , Transdução de Sinais
19.
J Cell Biochem ; 121(1): 557-565, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31338903

RESUMO

Early diagnosis of gastric cancer (GC) is an effective method to improve prognosis. Increasing number of long noncoding RNAs (lncRNAs) have been reported as biomarkers for several cancers. We aim to detect the level of lncRNA B3GALT5-AS1 and its association with clinical parameters and to further explore its application value in GC. We measured serum B3GALT5-AS1 expression in 107 patients with GC, 40 polyp patients, and 87 normal controls to explore the significance of serum B3GALT5-AS1 in GC using the quantitative real-time polymerase chain reaction method. The result demonstrated that B3GALT5-AS1 level was markedly richer in GC patients than that in normal people (P < .001). B3GALT5-AS1 may be served as a diagnostic marker for distinguishing GC patients from healthy people, and the proportion under the receiver operating characteristics curve is 0.816 (95% confidence interval, 0.758-0.874; P = .03). Further exploration validated that high serum B3GALT5-AS1 level was related to TNM stage (P = .024), and lymph node metastasis (P = .023). Our study suggested that serum B3GALT5-AS1 may be employed as an ideal biomarker for early screening of GC.


Assuntos
Adenocarcinoma/secundário , Biomarcadores Tumorais/genética , Galactosiltransferases/genética , Gastrectomia/mortalidade , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Neoplasias Gástricas/patologia , Adenocarcinoma/genética , Adenocarcinoma/cirurgia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Antissenso/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida
20.
Mol Cancer ; 19(1): 100, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32487159

RESUMO

In recent years, the prevalence and spread of coronavirus has had a huge impact on global public health. Due to the incomplete understanding of the pathogenic mechanism of the virus, it is difficult for humans to fight against the virus quickly and effectively once the outbreak occurs. In early 2020, a novel coronavirus was discovered in Wuhan, China. Soon after, similar cases were found in other countries around the world, and the number of infected people increased rapidly. So far, the global cumulative number of infected people has exceeded 3 million, and more than 200,000 people have died, which has had a huge impact on global human health and economic development. Every outbreak of disease makes a deep impression on mankind. Herein, we summarize the virology, epidemiology, clinical manifestations, diagnosis, treatment and prevention of SARS-CoV-2, and hope that countries can control the outbreak as soon as possible to minimize the loss.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Adulto , Betacoronavirus/fisiologia , COVID-19 , Criança , Infecções por Coronavirus/transmissão , Surtos de Doenças , Pessoal de Saúde , Humanos , Período de Incubação de Doenças Infecciosas , Saúde Mental , Pandemias , Pneumonia Viral/transmissão , SARS-CoV-2 , Mídias Sociais
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