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J Cell Physiol ; 235(11): 7757-7768, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-31742692

RESUMO

Long noncoding RNAs (lncRNAs) play a crucial role in several malignances, involving nasopharyngeal carcinoma (NPC), a heterogeneous disease. This study investigated mechanism of serine/arginine repetitive matrix protein 2-alternative splicing (SRRM2-AS) in NPC cell proliferation, differentiation, and angiogenesis. Initially, differentially expressed lncRNAs were screened out via microarray analysis. Vascular endothelial growth factor (VEGF) protein positive rate and microvessel density (MVD) were determined in NPC and adjacent tissues. NPC CNE-2 cells were treated with a series of vector and small interfering RNA to explore the effect of SRRM2-AS in NPC. The target relationship between myosin light chain kinase (MYLK) and SRRM2-AS was verified. Levels of SRRM2-AS, MYLK, cGMP, PKG, VEGF, PCNA, Ki-67, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and Caspase 3 were determined after transfection. Finally, the effect of SRRM2-AS on cell proliferation, colony formation, angiogenesis, cell cycle, and apoptosis in NPC was evaluated. SRRM2-AS was highly expressed and MYLK was poorly expressed in NPC tissues. VEGF protein positive rate and MVD were elevated in NPC tissues. MYLK was confirmed to be a target gene of SRRM2-AS. Silencing of SRRM2-AS elevated levels of MYLK, cGMP, PKG, Bax, and Caspase 3, but decreased levels of VEGF, PCNA, Ki-67, and Bcl-2. Especially, silencing of SRRM2-AS suppressed cell proliferation, colony formation and angiogenesis, blocked cell cycle, and enhanced cell apoptosis in NPC. Our results suggested that silencing of SRRM2-AS protected against angiogenesis of NPC cells by upregulating MYLK and activating the cGMP-PKG signaling pathway, which provides a new target for NPC treatment.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Quinase de Cadeia Leve de Miosina/metabolismo , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Neovascularização Patológica/genética , Proteínas de Ligação a RNA/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Processamento Alternativo , Proteínas de Ligação ao Cálcio/genética , Proteínas Quinases Dependentes de GMP Cíclico/genética , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Quinase de Cadeia Leve de Miosina/genética , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA/metabolismo
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