RESUMO
The long noncoding RNA MNX1-AS1 has been reported to facilitate the progression of glioblastoma and ovarian cancer. Nevertheless, the biological roles and underlying mechanisms of MNX1-AS1 in colon adenocarcinoma have not been studied until now. In the current study, MNX1-AS1 was upregulated in colon adenocarcinoma. JASPAR prediction tool showed that E2F1 could bind to the promoter region of MNX1-AS1. The chromatin immunoprecipitation assay and luciferase reporter assay were used to verify the interactions between MNX1-AS1 and E2F1. Then functional assays revealed that downregulation of MNX1-AS1 decreased cell proliferation, migration, and invasion in colon adenocarcinoma, but upregulation of E2F1 reversed the effects. Moreover, subcellular fractionation assay manifested that MNX1-AS1 was enriched in the cytoplasm of colon adenocarcinoma cells, thus we speculated whether MNX1-AS1 could function as a competing endogenous RNA (ceRNA) to play roles in colon adenocarcinoma. Bioinformatics analysis and luciferase reporter assay indicated that MNX1-AS1 could sponge microRNA-218-5p (miR-218-5p). Furthermore, we discovered that SEC61A1 was downstream target of miR-218-5p, and MNX1-AS1 acted as a ceRNA to upregulate the expression of SEC61A1 through sponging miR-218-5p. Finally, rescue assays confirmed that MNX1-AS1 facilitated the progression of colon adenocarcinoma through regulating miR-218-5p/SEC61A1 axis. Taken together, we concluded that E2F1-mediated MNX1-AS1-miR-218-5p-SEC61A1 feedback loop contributed to the progression of colon adenocarcinoma.
Assuntos
Adenocarcinoma/metabolismo , Neoplasias do Colo/metabolismo , Fator de Transcrição E2F1/metabolismo , Proteínas de Homeodomínio/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Canais de Translocação SEC/metabolismo , Fatores de Transcrição/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Western Blotting , Linhagem Celular Tumoral , Movimento Celular/genética , Movimento Celular/fisiologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Progressão da Doença , Fator de Transcrição E2F1/genética , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Células HT29 , Proteínas de Homeodomínio/genética , Humanos , Técnicas In Vitro , MicroRNAs/genética , RNA Longo não Codificante/genética , Canais de Translocação SEC/genética , Fatores de Transcrição/genéticaRESUMO
Introduction: It has been reported that long noncoding RNAs (lncRNAs) are crucial regulators in progression of human cancers, including colorectal cancer (CRC). However, the function of lncRNA ARAP1 antisense RNA 1 (ARAP1-AS1) in CRC remains unclear. Aim: The aim of this study was to investigate the function and molecular mechanism of lncRNA ARAP1-AS1 in CRC. Results: ARAP1-AS1 was highly expressed in CRC tissues and cell lines. ARAP1-AS1 knockdown suppressed cell migration, invasion, and epithelial-mesenchymal transition (EMT). YY1 transcription factor (YY1) enhanced the transcription activity of ARAP1-AS1. The YY1/ARAP1-AS1 axis promoted CRC cell migration and invasion. YY1/ARAP1-AS1 could regulate the Wnt/ß-catenin signaling pathway. Conclusions: This study revealed that YY1-induced upregulation of ARAP1-AS1 promoted cell migration, invasion, and EMT process in CRC through the Wnt/ß-catenin signaling pathway.