RESUMO
BACKGROUND: Bladder cancer (BCa) is a common genitourinary malignancy with higher incidence in males. Long intergenic non-protein coding RNA 265 (LINC00265) is identified as an oncogene in many malignancies, while its role in BCa development remains unknown. PURPOSE: To explore the functions and mechanism of LINC00265 in BCa. RESEARCH DESIGN: Reverse transcription quantitative polymerase chain reaction was performed to examine LINC00265 expression in BCa cells. Cell counting kit-8 assays, colony formation assays, TdT-mediated dUTP Nick-End Labeling assays, and Transwell assays were conducted to examine BCa cell viability, proliferation, apoptosis, and migration. Luciferase reporter assays and RNA immunoprecipitation assays were carried out to explore the binding capacity between miR-4677-3p and messenger RNA fibroblast growth factor 6 (FGF6) (or LINC00265). Xenograft tumor model was established to explore the role of LINC00265 in vivo. RESULTS: LINC00265 was highly expressed in BCa cells. LINC00265 knockdown inhibited xenograft tumor growth and BCa cell viability, proliferation and migration while enhancing cell apoptosis. Moreover, LINC00265 interacted with miR-4677-3p to upregulate the expression of FGF6. FGF6 overexpression reversed the suppressive effect of LINC00265 knockdown on malignant phenotypes of BCa cells. CONCLUSIONS: LINC00265 promotes the viability, proliferation, and migration of BCa cells by binding with miR-4677-3p to upregulate FGF6 expression.
Assuntos
Sobrevivência Celular , Fator 6 de Crescimento de Fibroblastos , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante , Animais , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular/fisiologia , Fator 6 de Crescimento de Fibroblastos/genética , Fator 6 de Crescimento de Fibroblastos/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Camundongos Nus , Neoplasias Experimentais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
Atherosclerosis is a chronic progressive inflammatory vascular disease. The dysfunction of vascular smooth muscle cells (VSMCs) induced by oxidized low-density lipoprotein (ox-LDL) contributes to the formation of atherosclerotic lesions. Additionally, upregulation of the long non-coding RNA zinc finger antisense 1 (ZFAS1) was observed in the plaques of patients with atherosclerosis. The aim of the present study was to explore the functional role of ZFAS1 in atherosclerosis progression. Reverse transcription-quantitative PCR was performed to analyze ZFAS1 mRNA expression, and western blotting was performed to determine the protein expression levels of Ki67, proliferating cell nuclear antigen (PCNA), matrix metallopeptidase (MMP)2 and MMP9. The Cell Counting Kit-8 assay was used to test cell viability. Finally, wound healing and Transwell chamber assays were performed to evaluate cell migration and invasion, respectively. The current findings demonstrated that ZFAS1 expression was upregulated by ox-LDL stimulation in VSMCs. Moreover, ZFAS1 overexpression promoted the ox-LDL-induced proliferation, migration and invasion of VSMCs, and upregulated the expression levels of proteins associated with cellular proliferation (Ki67 and PCNA), migration and invasion (MMP2 and 9). By contrast, ZFAS1-knockdown inhibited the proliferation, migration and invasion of VSMCs, and suppressed cell proliferation-, migration- and invasion-associated protein expression. In conclusion, ZFAS1 promoted the ox-LDL-induced proliferation, invasion and migration of VSMCs. Thus, ZFAS1 may represent a novel biomarker for dysfunction of VSMCs in the pathological condition of atherosclerosis.
