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Clin Exp Pharmacol Physiol ; 49(1): 175-187, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34546569

RESUMO

Cervical cancer (CC) is a common gynaecological malignant tumour with a high mortality rate. Circular RNAs (circRNAs) play a critical role in tumour occurrence and development. This study aimed to investigate the function and molecular basis of hsa_circ_0009189 (circSAMD11) in CC development. RNA levels were determined by qRT-PCR, and protein expression was measured by western blot. Cell proliferation, migration, invasion and apoptosis were detected by Cell Counting Kit-8 (CCK-8), colony formation, Transwell and flow cytometry assays. The relationship between miR-503 and circSAMD11/SOX4 was validated via dual-luciferase reporter assay, RIP or RNA pull-down assay. Xenograft assay was conducted to test tumour growth in vivo. CircSAMD11 and SOX4 levels were elevated, while miR-503 level was reduced in CC tissues and cells. Knockdown of circSAMD11 suppressed CC cell proliferation, migration and invasion and accelerated apoptosis. CircSAMD11 was localised in cytoplasm and directly targeted miR-503. Also, circSAMD11 sponged miR-503 to modulate SOX4 expression. Additionally, circSAMD11 regulated CC progression via absorbing miR-503 or modulating SOX4. Besides, depletion of circSAMD11 hindered tumorigenesis in vivo. CircSAMD11 contributed to CC progression by regulating miR-503/SOX4 signalling and activating Wnt/ß-catenin pathway, which provides a promising therapeutic target for cervical cancer.


Assuntos
Proteínas do Olho/genética , MicroRNAs/metabolismo , RNA Circular/metabolismo , RNA Neoplásico/metabolismo , Fatores de Transcrição SOXC/metabolismo , Neoplasias do Colo do Útero/metabolismo , Via de Sinalização Wnt , Animais , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Proteínas do Olho/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Transplante de Neoplasias , Neoplasias do Colo do Útero/patologia
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