Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 10 de 10
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Cell Mol Biol Lett ; 29(1): 97, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961325

RESUMO

BACKGROUND: Pancreatic cancer (PC) is one of the most malignant cancers with highly aggressiveness and poor prognosis. N6-methyladenosine (m6A) have been indicated to be involved in PC development. Glucan Branching Enzyme 1 (GBE1) is mainly involved in cell glycogen metabolism. However, the function of GBE1 and Whether GBE1 occurs m6A modification in PC progression remains to be illustrated. METHODS: The clinical prognosis of GBE1 was analyzed through online platform. The expression of GBE1 was obtained from online platform and then verified in normal and PC cell lines. Lentivirus was used to generated GBE1 stable-overexpression or knockdown PC cells. Cell Counting Kit (CCK-8), colony formation assay, sphere formation assay and flow cytometry assay were conducted to analyze cell proliferation and stemness ability in vitro. Subcutaneous and orthotopic mouse models were used to verify the function of GBE1 in vivo. RNA immunoprecipitation (RIP) assay, RNA stability experiment and western blots were conducted to explore the molecular regulation of GBE1 in PC. RESULTS: GBE1 was significantly upregulated in PC and associated with poor prognosis of PC patients. Functionally, GBE1 overexpression facilitated PC cell proliferation and stemness-like properties, while knockdown of GBE1 attenuated the malignancy of PC cells. Importantly, we found the m6A modification of GBE1 RNA, and WTAP and IGF2BP3 was revealed as the m6A regulators to increase GBE1 mRNA stability and expression. Furthermore, c-Myc was discovered as a downstream gene of GBE1 and functional rescue experiments showed that overexpression of c-Myc could rescue GBE1 knockdown-induced PC cell growth inhibition. CONCLUSIONS: Our study uncovered the oncogenic role of GBE1/c-Myc axis in PC progression and revealed WTAP/IGF2BP3-mediated m6A modification of GBE1, which highlight the potential application of GBE1 in the targeted therapy of PC.


Assuntos
Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Células-Tronco Neoplásicas , Neoplasias Pancreáticas , Proteínas Proto-Oncogênicas c-myc , Proteínas de Ligação a RNA , Regulação para Cima , Humanos , Proliferação de Células/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Linhagem Celular Tumoral , Animais , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Camundongos , Regulação para Cima/genética , Camundongos Nus , Prognóstico
2.
Clin. transl. oncol. (Print) ; 25(7): 1999-2014, jul. 2023. ilus
Artigo em Inglês | IBECS | ID: ibc-222374

RESUMO

Human resistance protein R (HuR), also known as embryonic lethal abnormal visual-like protein (ELAVL1), is an RNA-binding protein widely expressed in vivo that affects the mRNA stability of targeted and is involved in post-transcriptional regulation. Recent studies have shown that HuR is aberrantly expressed in different human cancers and is an essential factor in poor clinical prognosis. The role of HuR in numerous tumors suggests that it could be a new target for tumor therapy and as a marker for efficacy and prognostic assessment. This review focuses on the relationship between HuR and drug resistance in different tumors and briefly describes the structure, function, and inhibitors of HuR. We summarize the mechanisms by which HuR causes tumor resistance and the molecular targets affected (AU)


Assuntos
Humanos , Resistencia a Medicamentos Antineoplásicos/genética , Proteína Semelhante a ELAV 1/genética , Proteína Semelhante a ELAV 1/metabolismo , Neoplasias/genética , Neoplasias/terapia , Regulação Neoplásica da Expressão Gênica , Prognóstico
3.
Clin Transl Oncol ; 25(7): 1999-2014, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36947360

RESUMO

Human resistance protein R (HuR), also known as embryonic lethal abnormal visual-like protein (ELAVL1), is an RNA-binding protein widely expressed in vivo that affects the mRNA stability of targeted and is involved in post-transcriptional regulation. Recent studies have shown that HuR is aberrantly expressed in different human cancers and is an essential factor in poor clinical prognosis. The role of HuR in numerous tumors suggests that it could be a new target for tumor therapy and as a marker for efficacy and prognostic assessment. This review focuses on the relationship between HuR and drug resistance in different tumors and briefly describes the structure, function, and inhibitors of HuR. We summarize the mechanisms by which HuR causes tumor resistance and the molecular targets affected.


Assuntos
Proteína Semelhante a ELAV 1 , Neoplasias , Humanos , Proteína Semelhante a ELAV 1/genética , Proteína Semelhante a ELAV 1/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Regulação da Expressão Gênica , Resistencia a Medicamentos Antineoplásicos/genética , Prognóstico
4.
Front Oncol ; 13: 1088475, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36969045

RESUMO

Background: Hepatocellular carcinoma (HCC) is a common malignant tumor associated with a poor prognosis. Ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) has been reported to promote diverse tumors, but little is known about its role in HCC. Methods: Expression levels of UCHL3 in Huh7 and Hep3B cells were measured by qRT-PCR. UCHL3, Vimentin protein levels, and ubiquitination levels were determined by Western blot assay. co-immunoprecipitation, Immunofluorescence, and IHC were used to detect the interaction and expression association between UCHL3 and Vimentin in the cells. Wound healing and Transwell assays were used to measure cell migration. Spheroid formation assay were used to assess stem-like properties. Results: UCHL3 expression was found to be significantly elevated in HCC and associated with poor prognosis. UCHL3 promoted migration and stem-like properties of HCC cells. Vimentin was identified as a potential de-ubiquitination substrate of UCHL3 and UCHL3 interacted with and promoted the de-ubiquitination of Vimentin, enhancing its stability. Moreover, the suppression of UCHL3 by siRNA or the inhibition by TCID upregulated ubiquitinated Vimentin. Vimentin attenuated the suppression of cell migration caused by knockdown of UCHL3. Conclusion: UCHL3 was highly expressed in HCC and functioned as an oncogene. Vimentin is a novel substrate of UCHL3 and its stabilization and de-ubiquitination enhanced HCC cell migration.

5.
Int J Oncol ; 62(4)2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36896783

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a noteworthy malignant carcinoma with an unsatisfactory prognosis attributed to late diagnosis. Ubiquitin­conjugating enzyme E2K (UBE2K) has been found to serve important roles in a number of diseases. However, its function and the exact molecular mechanism of UBE2K in PDAC remain to be elucidated. The present study discovered that UBE2K was expressed at high levels and indicated the poor prognosis of patients with PDAC. Following this, the CCK­8, colony formation, and sphere formation assays showed that UBE2K promoted proliferation and the stemness phenotype of PDAC cells in vitro. Evidence from subcutaneous tumor­bearing nude mice experiments further confirmed that UBE2K enhanced PDAC cell tumorigenesis in vivo. Additionally, the present study demonstrated that insulin­like growth factor 2 RNA binding protein 3 (IGF2BP3) functioned as an RNA­binding protein to increase UBE2K expression by enhancing the RNA stability of UBE2K. The knockdown or overexpression of IGF2BP3 could attenuate the change in cells growth induced by the overexpression or knockdown of UBE2K. In summary, the findings indicated the oncogenic roles of UBE2K in PDAC. In addition, IGF2BP3 and UBE2K constitute a functional axis to regulate the malignant progression of PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Camundongos , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Neoplasias Pancreáticas/patologia , Prognóstico , RNA , Neoplasias Pancreáticas
6.
Pathol Res Pract ; 243: 154377, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36827886

RESUMO

BACKGROUND: Long non-cording RNAs (lncRNAs) drive the malignant progression of hepatocellular carcinoma (HCC), a cancer with high mortality rates but the function of FERM Domain Containing 6 antisense RNA 1 (FRMD6-AS1) in HCC has not been fully addressed. Hypoxia-inducible factors (HIFs) are transcription factors relevant to HCC under hypoxia and are regulated by SUMO-specific protease 1 (SENP1) through its deSUMOylation of HIF-1α. The current study investigated the role of FRMD6-AS1 in the regulation of SENP1-mediated deSUMOylation of HIF-1α. METHODS: HUH7 and MHCC97H cells were treated with CoCl2 to mimic hypoxia in vitro and lentiviral vector-mediated FRMD6-AS1 overexpressing HCC cells were established. Wound-healing, Transwell, sphere formation assay, Western blotting analysis and animal experiments were performed. Expression of FRMD6-AS1, SENP1 mRNA and HIF-1α mRNA was assessed by RT-qPCR and of HIF-1α and SENP1 protein by Western blot. DeSUMOylation of HIF-1α was detected by immunoprecipitation. RNA immunoprecipitation with SENP1 antibody or IgG was performed to assess endogenous interactions between SENP1 and FRMD6-AS1. RESULTS: FRMD6-AS1 was upregulated in HCC tissues and cells and its upregulation indicated poor prognosis for HCC patients. FRMD6-AS1 promoted HCC cells migration and stemness in vitro and also promoted tumor growth in an in vivo mouse xenograft model. Mechanistic studies showed that FRMD6-AS1 regulated the level of HIF-1α protein but not the mRNA and this effect was achieved by binding to SENP1 protein and enhancing its protease activity. Rescue experiments demonstrated the oncogenic role of the FRMD6-AS1/SENP1/ HIF-1α axis in HCC cells. CONCLUSIONS: High FRMD6-AS1 expression was associated with poor prognosis of HCC patients. FRMD6-AS1 may have an oncogenic role in HCC via regulation of the SENP1/HIF-1α axis and may be a prognostic biomarker for HCC. Blockade of FRMD6-AS1 may offer a novel therapeutic approach to restrict HCC progression.


Assuntos
Carcinoma Hepatocelular , Cisteína Endopeptidases , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante , Animais , Humanos , Camundongos , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Proteínas do Citoesqueleto/metabolismo , Regulação Neoplásica da Expressão Gênica , Hipóxia , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Peptídeo Hidrolases/genética , Peptídeo Hidrolases/metabolismo , RNA Longo não Codificante/genética , RNA Mensageiro
7.
Oncol Rep ; 49(3)2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36799184

RESUMO

Digestive system cancers are the leading cause of cancer­related death worldwide due to their high morbidity and mortality rates. The current treatment methods include surgical treatment, chemotherapy, radiotherapy and endoscopic treatment, and the precisely targeted therapy of digestive system cancers requires to be further studied. The ubiquitin­proteasome system is the main pathway for protein degradation in cells and the ubiquitin­conjugating enzymes (E2s) have a decisive role in the specific selection of target proteins for degradation. The E2s have an important physiological role in digestive system cancers, which is related to the clinical tumor stage, differentiation degree and poor prognosis. Furthermore, they are involved in the physiological processes of digestive system tumor cell proliferation, migration, invasion, stemness, drug resistance and autophagy. In the present article, the progress and achievements of the E2s in gastric cancer, hepatocellular carcinoma, pancreatic cancer, colorectal cancer, intrahepatic cholangiocarcinoma, gallbladder cancer and esophageal squamous cell carcinoma were reviewed, which may provide early screening indicators and reliable therapeutic targets for digestive system cancers.


Assuntos
Neoplasias do Sistema Digestório , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias Hepáticas , Humanos , Enzimas de Conjugação de Ubiquitina/genética , Neoplasias do Sistema Digestório/diagnóstico , Neoplasias do Sistema Digestório/genética , Neoplasias do Sistema Digestório/terapia , Biomarcadores Tumorais/genética
8.
Biochem Biophys Res Commun ; 638: 210-218, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36481361

RESUMO

Hepatocellular carcinoma (HCC) is a serious threat to human health and life due to its high morbidity and mortality. Ubiquitin-conjugating enzymes are players in the ubiquitin proteasome system and are responsible for a great number of physiological activities in cells. The action of ubiquitin-conjugating enzyme UBE2K in HCC has not been reported. Therefore, we studied the function and role of UBE2K in the malignant progression of HCC. An analysis of UBE2K expression in HCC cells was performed using RT-qPCR and protein immunoblotting. CCK-8, Transwell and sphere formation assays were used to identify the potential effects of UBE2K in HCC cell proliferation, migration and stemness property. RT-qPCR, and protein immunoblotting experiments was taken to explore the regulation between UBE2K and c-Myc. Here, we discovered that UBE2K expression was elevated in HCC cells, and elevated UBE2K predicts worse prognosis for HCC patients. Functionally, UBE2K promote, while UBE2K knockdown suppressed cell proliferation, migration and stemness property of HCC cells. Furthermore, c-Myc was identified as a downstream target of UBE2K. Moreover, functional rescue experiments finally proved that UBE2K facilitates the malignant progression of HCC cells by upregulating c-Myc. We clarified through in vivo experiments that UBE2K expression promotes tumor growth in HCC. Taken together, our study results proved the molecular regulation of UBE2K and c-Myc in HCC and the oncogenic role of UBE2K/c-Myc axis in HCC progression, thus it provides a promising molecular target for the diagnosis and treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Linhagem Celular , Proliferação de Células , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismo
9.
J Cell Mol Med ; 26(20): 5292-5302, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36098205

RESUMO

Long noncoding RNAs (lncRNAs) are confirmed as the key regulators of hepatocellular carcinoma (HCC) occurrence and progression, but the role of AlkB homologue 3 antisense RNA 1 (ALKBH3-AS1) in HCC is unclear. We revealed the overexpression of ALKBH3-AS1 in HCC tissues. The upregulated levels of ALKBH3-AS1 were observed in HCC cells. ALKBH3-AS1 was expressed in the nucleus and cytoplasm of HCC cells. The high ALKBH3-AS1 expression was markedly associated with a decreased survival rate of HCC patients. ALKBH3-AS1 knockdown repressed and ALKBH3-AS1 overexpression enhanced HCC cell invasion and proliferation. ALKBH3-AS1 silencing restricted HCC growth in vivo. A significant positive correlation between ALKBH3-AS1 and ALKBH3 mRNA levels was confirmed in HCC specimens. ALKBH3-AS1 silencing reduced ALKBH3 expression by stabilizing its mRNA stability in HCC cells. Notably, the impact of ALKBH3 silencing on HCC cells was similar to that of ALKBH3-AS1 knockdown. ALKBH3 restoration prominently attenuated the suppressive effects resulting from ALKBH3-AS1 silencing in HCCLM3 cells. Hypoxia-inducible factor-1α (HIF-1α) transcriptionally activated ALKBH3-AS1 expression in hypoxic HCC cells. ALKBH3-AS1 knockdown markedly attenuated cell proliferation and invasion in hypoxic Huh7 cells. Collectively, HIF-1α-activated ALKBH3-AS1 exerted an oncogenic role by enhancing ALKBH3 mRNA stability in HCC cells.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Estabilidade de RNA , RNA Longo não Codificante , Homólogo AlkB 3 da Dioxigenase Dependente de alfa-Cetoglutarato/genética , Homólogo AlkB 3 da Dioxigenase Dependente de alfa-Cetoglutarato/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas/patologia , MicroRNAs/genética , RNA Antissenso , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética
10.
Front Oncol ; 12: 927640, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936737

RESUMO

Pancreatic cancer (PC) is one of the most common malignant cancers, ranking the seventh highest causes of cancer-related deaths globally. Recently, RNA N6-methyladenosine (m6A) is emerging as one of the most abundant RNA modifications in eukaryote cells, involved in multiple RNA processes including RNA translocation, alternative splicing, maturation, stability, and degradation. As reported, m6A was dynamically and reversibly regulated by its "writers", "erasers", and "readers", Increasing evidence has revealed the vital role of m6A modification in the development of multiple types of cancers including PC. Currently, aberrant m6A modification level has been found in both PC tissues and cell lines. Moreover, abnormal expressions of m6A regulators and m6A-modified genes have been reported to contribute to the malignant development of PC. Here in this review, we will focus on the function and molecular mechanism of m6A-modulated RNAs including coding RNAs as well as non-coding RNAs. Then the m6A regulators will be summarized to reveal their potential applications in the clinical diagnosis, prognosis, and therapeutics of PC.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...