RESUMEN
Bladder cancer (BC) is one of the most aggressive tumors worldwide. OTX1 (orthodenticle homeobox 1) is an important transcription factor involved in various diseases, such as cancers. The aim of this study was to further investigate the role of OTX1 in BC. In this study, differentially expressed genes (DEGs) were screened from tumor tissues and para-cancerous tissues by bioinformatics. The expression of protein and RNA was separately detected by western blotting and immunohistochemistry (IHC), and quantitative polymerase chain reaction (qPCR); cell viability and cell growth were determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays, respectively; cell motility was measured by transwell and wound healing assays; cell cycle was measured by flow cytometry. In this study, 9 DEGs were screened out, and OTX1 was employed as a candidate gene for subsequent study. Results found that OTX1 was highly expressed in BC cells and BC tissues, which was significantly associated with poor prognosis of patients. In addition, OTX1 silencing significantly reduced cell viability, and inhibited cell growth and motility, while OTX1 overexpression got opposite results. Moreover, OTX1 co-expressed genes were enriched in cell cycle-related pathways, suggesting that the role of OTX1 in BC may be related to cell cycle, which was confirmed by flow cytometry analysis. Furthermore, in vivo experiments showed that OTX1 silencing significantly inhibited tumor growth in tumor-bearing mice. Taken together, our findings suggested that OTX1 may play a promotional role in BC progression.
Asunto(s)
Factores de Transcripción Otx/genética , Neoplasias de la Vejiga Urinaria , Anciano , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Femenino , Humanos , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Factores de Transcripción Otx/metabolismo , Pronóstico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/mortalidadRESUMEN
BACKGROUND: Orthodenticle homeobox 1 (OTX1) is a transcription factor that plays an important role in various human cancers. However, the function of OTX1 in laryngeal squamous cell carcinoma (LSCC) is largely unknown. We aimed to explore the roles of OTX1 in LSCC and its possible molecular mechanism. METHODS: The expression levels of OTX1 were assessed in LSCC cell lines and tissue samples. We further examined the effect of OTX1 on LSCC progression. The upstream regulator of OTX1 was identified using a computer algorithm and confirmed experimentally. RESULTS: OTX1 was highly expressed in 70.7% (70/99) of LSCC tissue samples. The OTX1 expression in LSCC was significantly correlated with lymph node metastasis. High OTX1 expression in patients with LSCC was correlated with poor prognosis. Knockdown of OTX1 inhibited proliferation, colony formation, migration and invasion in LSCC cells. Knockdown of OTX1 inhibited tumor growth in a xenograft mouse model. Mechanistically, OTX1 might act as a direct target of miR-129-5p. OTX1 enhanced tumorigenicity and tumor growth both in vitro and in vivo. CONCLUSIONS: Our findings support that OTX1 is an oncogene in LSCC tumorigenesis and progression. Furthermore, OTX1 is a direct target of miR-129-5p in LSCC cells. Taken together, OTX1 is a promising diagnostic and therapeutic marker for LSCC.