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1.
J Exp Clin Cancer Res ; 41(1): 77, 2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35209949

RESUMO

BACKGROUND: Metabolic reprogramming is a hallmark of cancer. However, the roles of long noncoding RNAs (lncRNAs) in cancer metabolism, especially glucose metabolism remain largely unknown. RESULTS: In this study, we identified and functionally characterized a novel metabolism-related lncRNA, LINC00930, which was upregulated and associated with tumorigenesis, lymphatic invasion, metastasis, and poor prognosis in nasopharyngeal carcinoma (NPC). Functionally, LINC00930 was required for increased glycolysis activity and cell proliferation in multiple NPC models in vitro and in vivo. Mechanistically, LINC00930 served as a scaffold to recruit the RBBP5 and GCN5 complex to the PFKFB3 promoter and increased H3K4 trimethylation and H3K9 acetylation levels in the PFKFB3 promoter region, which epigenetically transactivating PFKFB3, and thus promoting glycolytic flux and cell cycle progression. Clinically, targeting LINC00930 and PFKFB3 in combination with radiotherapy induced tumor regression. CONCLUSIONS: Collectively, LINC00930 is mechanistically, functionally and clinically oncogenic in NPC. Targeting LINC00930 and its pathway may be meaningful for treating patients with NPC.


Assuntos
Glicólise/genética , Neoplasias Nasofaríngeas/genética , Oncogenes/genética , Fosfofrutoquinase-2/metabolismo , RNA Longo não Codificante/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Neoplasias Nasofaríngeas/patologia , Transfecção
2.
Biochem Biophys Res Commun ; 551: 100-106, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33725570

RESUMO

Colorectal cancer (CRC) is prevalent worldwide and novel diagnostic and prognostic biomarkers are needed to improve precision medicine. Circular RNAs (circRNAs) are currently being considered as emerging tumor biomarkers. Herein, we aimed to explore the possible clinical application of circRNAs in the early diagnosis and prognostic prediction of CRC. First, candidate circRNA was selected by integrating analysis of Gene Expression Omnibus (GEO) database using GEO2R program. ROC curve analysis demonstrated the predictive values and likelihood ratios of circ_001659 were satisfactory for the diagnosis of CRC, including patients in early-stage disease or patients with carcinoembryonic antigen (CEA)-negative status. Moreover, serum circ_001659 may be a novel biomarker in the assessment of successful treatment and remission of cancer tracking. We further investigated the oncogenic role of circ_001659. In vivo and in vitro experiments indicated that circ_001659 could promote CRC cell invasion and migration. Mechanistically, circ_001659 was localized in the nucleus, recruited the RBBP5 to Vimentin promoter and increased H3K4 trimethylation level on the Vimentin promoter region, which epigenetically activated Vimentin transcription. Our findings demonstrate that circ_001659 could be a useful serum biomarker for CRC diagnosis and prognosis. Targeting circ_001659 and its pathway may be meaningful for treating patients with CRC.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Metástase Neoplásica , RNA Circular/sangue , Animais , Biomarcadores Tumorais/genética , Antígeno Carcinoembrionário/sangue , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Proteínas de Ligação a DNA/metabolismo , Epigênese Genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica/genética , Prognóstico , Regiões Promotoras Genéticas/genética , RNA Circular/genética , Transcrição Gênica , Vimentina/genética
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